Measuring and interpreting Blood hCG to Assess Pregnancy Viability Following ART Treatments

I know of no medical announcement associated with the degree of emotional anticipation and anguish as that associated with a pending diagnosis/confirmation of pregnancy following infertility treatment. In fact, hardly a day goes by where I am not confronted by a patient anxiously seeking interpretation of a pregnancy test result.

Testing urine or blood for the presence of human chorionic gonadotropin (hCG) is the most effective and reliable way to confirm conception. The former, is far less expensive than the latter and is the most common method used. It is also more convenient because it can be performed in the convenience of the home setting. However, urine hCG testing for pregnancy is not nearly as reliable or as sensitive e as is blood hCG testing. Blood testing can detect implantation several days earlier than can a urine test. Modern pregnancy urine test kits can detect hCG about 16-18 days following ovulation (or 2-3 days after having missed a menstrual period), while blood tests can detect hCG, 12-13 days post-ovulation (i.e. even prior to menstruation).

The ability to detect hCG in the blood as early as possible and thereupon to track its increase, is particularly valuable in women undergoing controlled ovarian stimulation (COS) with or without intrauterine insemination (IUI) or after IVF. The earlier hCG can be detected in the blood and its concentration measured, the sooner levels can be tracked serially over time and so provide valuable information about the effectiveness of implantation, and the potential viability of the developing conceptus.

There are a few important points that should be considered when it comes to measuring interpreting blood hCG levels. These include the following:

  • All modern day blood (and urine) hCG tests are highly specific in that they measure exclusively for hCG. There is in fact no cross-reactivity with other hormones such as estrogen, progesterone or LH.
  • Post conception hCG levels, measured 10 days post ovulation or egg retrieval can vary widely (ranging from 5mIU/ml to above 400mIU/ml. The level will double every 48–72 hours up to the 6th week of gestation whereupon the doubling rate starts to slow down to about 96 hours. An hCG level of 13,000-290, 0000 mIU/ml is reached by the end of the 1st trimester (12 weeks) whereupon it slowly declines to approximately 26,000– 300,000 mIU/ml by full term. Below are the average hCG levels during the first trimester:
    • 3 weeks LMP: 5 – 50 mIU/ml
    • 4 weeks LMP: 5 – 426 mIU/ml
    • 5 weeks LMP: 18 – 7,340 mIU/ml
    • 6 weeks LMP: 1,080 – 56,500 mIU/ml
    • 7 – 8 weeks LMP: 7, 650 – 229,000 mIU/ml
    • 9 – 12 weeks LMP: 25,700 – 288,000 mIU/ml
    • A single hCG blood level is not sufficient to assess the viability of an implanting embryo. Caution should be used in making too much of an initial hCG level. This is because a normal pregnancy can start with relatively low hCG blood levels. It is the rate of the rise of the blood hCG level that is relevant.
    • In some cases the initially hCG level is within the normal range, but then fails to double in the ensuing 48-72hours. In some cases it might even plateau or decline, only to start doubling appropriately thereafter. When this happens, it could be due to:
      • A recovering implantation, destined to develop into a clinical gestation
      • A failing implantation (a chemical pregnancy)
      • A multiple pregnancy which is spontaneously reducing (i.e., one or more of the concepti is being lost) or,
      • An ectopic pregnancy which will either absorb spontaneously (a chemical-tubal gestation), or evolve into a full blown tubal pregnancy continue and declare itself through characteristic symptoms and signs of an intraperitoneal bleed.
  •  The blood hCG test needs to be repeated at least once after 48h and in some cases it  will need to be repeated one or more times (at 48h intervals) thereafter, to confirm that implantation is progressing normally.
  • Ultimately the diagnosis of a viable pregnancy requires confirmation of the presence of an intrauterine gestational sac by ultrasound examination. The earliest that this can be achieved is when the beta hCG level exceeds 1,000mIU/ml (i.e., around 5-6 weeks).
  • Most physicians prefer to defer the performance of a routine US diagnosis of pregnancy until closer to the 7th week. This is because by that time, cardiac activity should be clearly detectable, allowing for more reliable assessment of pregnancy viability.
  • There are cases where the blood beta hCG level is extraordinarily high or the rate of rise is well above the normal doubling rate. The commonest explanation is that more than one pregnancy has implanted. However in some cases it can point to a molar pregnancy  
  • Finally, there on rare occasions, conditions unrelated to pregnancy can result in detectable hCG levels in blood and urine. They include ovarian tumors that produce hCG, such as certain types of cystic teratomas (dermoid cysts) and some ovarian cancers such as dysgerminomas.

2,478 Comments

Emily Riddick

Dr Sher,

I am on my third round of IVF with no successful pregnancies. We transferred two normal tested PGS embryos after a mock cycle with a endometrial biopsy with no issues identified. I got a positive on a home test on 6dp5dt that got darker until 11dp5dt when the line started to get lighter until it was almost non existent. My first beta was 21.6 13dp5dt which I know is low. I am having the lines reappear darker though since this first beta was drawn I have the second beta scheduled for this Friday. Is this a positive sign that I could still be pregnant? I am trying to stay hopeful but I want to remain realistic as well.

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Dr. Geoffrey Sher

I would do more beta hCG tests 2 days apart to see if the level keeps doubling!

Good luck!

Geoff Sher

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A

Hello- Could you explain the expected doubling rate for HCG in weeks 4-5 of pregnancy? Mine is going up around 67% every 48 hours. Some sources say a minimum of 60% rise every 48 hours is fine, but others seem to say it should really double. My numbers have been 114, 189, 315, each done 48 hours apart, which again, is around 67% increase each time. What do you think? Why do sources seem to be so different in recommendations for rise?

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Dr. Geoffrey Sher

The range of normal rise can and often does vary slightly. You will need to have an US at 6-7 weeks for a definitive answer as to potential viability of the pregnancy.

Good luck!

Geoff Sher

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Alie

Any chance you could offer insight? I took letraolze with ovadril trigger on 8/14 in the evening.. Pregnancy test positive August 31 with hcg of 118 and progesterone of 28. On September 2nd hcg was 189 and today, September 4th, hcg was 316. They seem concerned and want me back on Tuesday- in 4 days for another hcg test. How concerned would you be about this? Thank you so much!

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Noelle

Hi Dr. Sheri

I am 42 years old doing IUI with Femara. I recently had the IUI on August 19, then was instructed to test 2 weeks later (September 2), which yielded positive. I had labs taken that day and my beta Hcg was 34, then I repeated 2 days later Friday September 4, and it was 134. Today (Sunday September 6) my hcg was 415. My RE wants to do an ultrasound this coming Friday 9/11. Do you think this could potentially be a viable pregnancy? When I look at the ranges according to when the cycle occurred I’m 2 weeks, but I believe the calculations is a little different with IUI. I’m confused. What do you think? I’m trying to be optimistic but I don’t want to get my hopes up too high.

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Portia

Greeting to the good Dr.
First day of last period was 19 July. My HCG reading done on 02 Sept was 1860. I have had 2 miscarriages this year, one in Jan and the other in June where I had a D&C procedure. Could this be another sign of a non viable pregnancy?

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Eliza

Hi – I transferred 2 frozen embryos on 8/17. I took my first home pregnancy test on 8/21 and got a faint positive. I continued to take a home pregnancy test every morning for the next 3 mornings and the line got noticeably darker each day until it was a similar to the control line.

My initial beta on 8/26 was 109
However, the 2nd beta on 8/28 was 151 which surprised me since the home tests consistently got dark each day rather early post transfer
I had a third beta completed on 8/31 which was 504.

Given the smaller increase btwn betas 1 and 2 and the large jump from beta 2 to 3 – does this sound like a possible viable pregnancy? Any reason why it would seemingly increase steadily for the hpt, then not increase optimally btwn betas 1-2 and jump so much for 3?

My dr has ordered another blood test 9/2 and I dont know what to prepare myself for

Thank you!

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Dr. Geoffrey Sher

Hard to explain, but this could well still be a viable implantation.

Good luck!

Geoff Sher

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Dee

Hello Doctor,

I am currently 5 weeks and 6 days pregnant confirmed by an ultrasound Friday 8/28/20 when I was 5 weeks 3 days pregnant. We saw the gest sac and the yolk sac but no embryo. The doctor said we were just too early for the ultrasound and we will repeat on Sept 9th. Is this completely normal in your eyes to not be able to see the embryo at 5 weeks 3 days pregnant. Based on my LMP the doctor had calculated that I would have been 6 weeks 2 days at the ultrasound on 8/28. However I am 100% sure on our conception date and the ultrasound proved that. Thank you!

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pri586

Hi Dr Sher,

I need some insight on my fertility treatment-

I had done my first iui on 30th March 2020 with clomid and puregon injectibles. And I conceived but miscarried on 24th May as it was a blighted ovum (yolk sac was empty). My doctor asked to take two cycle break before we do second round of iui. Also since mid March, we are taking supplements prescribed by the doctor. I am taking CoQ10, Folic acid, Myoinositol and Nrurozan and my husband is taking Profertil and Motil.

My second iui happened on 13th August with clomid and 75 iu/ml per day. I had two follicles, one on left side and other one on right side. On 11th August both follicle size was 18 mm then I took one more puregon shot on 12th August and I triggered ovidrel in the afternoon. Even my husband’d sperm count was good on the day of insemination.

In TWW, I felt severe leg pain for two days and also I felt nauseous. But my pregnancy test came out as negative on 27th August (hcg is just 1.2). Now my doctor is recommending for third round of iui.

I would like to understand what could have gone wrong or how can we improve our chances in iui. When I ask this question to my doctor she gets away by saying, chances of pregnancy with iui are only 15% to 20%, let’s hope for the best. We eat healthy, no one smokes, I don’t have any fertility issues, I also ovulate naturally and get my periods regularly.

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Dr. Geoffrey Sher

Many infertile patients, are erroneously advised by their physicians to first try IUI several times before resorting to IVF. Additionally many misguided insurance providers often, purely for economic reasons, require that infertile female enrollees who have at least 1 patent Fallopian tube, first undergo several attempts at IUI before doing IVF. It is important for infertile women to be aware that such an approach is often ill-advised as there are circumstances where IUI is very unlikely to be successful and where IVF should be the primary approach.

While IUI is well indicated for women undergoing controlled ovarian stimulation for ovulation dysfunction, cervical mucus hostility, male impotence and when artificial insemination with pre-frozen sperm, there are several situations where in spite of tubal patency it is (in my opinion) relatively contraindicated:
• Moderate or severe male Infertility: Intrauterine insemination (IUI) and in-vitro fertilization (IVF) are both often touted as being equivalent treatments for male factor subfertility. This is a fallacy. The success rate with a single IVF treatment using intracytoplasmic sperm injection is actually 8-10 times greater than a single attempt at IUI. Thus when it comes to moderate or severe male infertility such patients will ultimately require IVF anyway. Those who argue that because a single cycle of IUI is much less expensive than a single attempt at IVF and for this reason, several attempts at the former should be tried before resorting to IVF. A recent study conducted by the Department of Public Health in the UK compared outcomes (live birth-producing pregnancy) and the cost-effectiveness of offering IVF as a primary approach as compared with first trying IUI and only resorting to IVF if this fails. The results confirmed that in cases of male factor infertility it is far less costly and much more cost-effective to go directly to IVF as the primary treatment than to start with IUI and then only resort to IVF, should this fail.
• Older women and those with Diminished ovarian reserve (DOR): For the vast majority of women, over 35y of age, an inevitable irreversible and accelerated advancement of the biological clock takes place, such that by age 40y there is only about a 2-3% per-cycle, chance of IUI success. Conversely IVF afford many such women a far greater opportunity to have a baby. Thus such women simply do not have the time to waste on ineffectual treatments such as IUI. Rather, they need (in my opinion) to “make hay while the sun still shines” and go directly to IVF.
• Endometriosis: All women with endometriosis have toxins in their pelvic secretions. This compromises the ability of sperm to fertilize eggs that pass from the ovary (ies) to reach sperm in the fallopian tube(s).This dramatically reduces egg fertilization potential by a factor of 4-6 fold. It in large part serves to explain why potentially all women with endometriosis have reduced fecundity (reproductive potential) and why tubal surgery, the use of fertility drugs and/or intrauterine insemination (IUI) does not improve fecundity over no treatment at all. The only way to improve the chance of having a baby through extracting eggs before they are exposed to toxic pelvic secretions…i.e. through IVF. I am not suggesting that all women with endometriosis should go directly to IVF. In fact most ovulating younger women with early endometriosis have time and should consider trying to conceive on their own. Rather, what I am saying is that women over 35y, regardless of age, those who have DOR and those women who for whatever reason feel a compelling sense of urgency to conceive ASAP, should preferentially consider doing IVF.
I would now like to try and dispel the following misconceptions regarding IUI:

i. The per-cycle cost of IUI is significantly lower than IVF and thus IUI represents a “cost saver”: Given the fact that IVF is at least 3-4 times more likely to be successful, when one looks at cost per baby (rather than cost per procedure) this turns out to be a fallacy. Moreover, cost also comes in the form of emotional currency and this needs to be measured in terms of the much lower chance of success with IUI.
ii. Success in ovulating women who undergo natural-cycle IUI and those women undergoing ovulation induction with clomiphene citrate is equivalent to success rates when gonadotropins are used: Quite to the contrary….,with the exception of IUI performed using thawed sperm (usually donor sperm), spontaneously ovulating women undergoing natural-cycle IUI does not improve the chance of pregnancy over regular timed intercourse. Also, when compared with IUI performed following induction of ovulation with gonadotropins, the use of clomiphene citrate is associated with a 30% lower success rate.
iii. “IUI is less invasive than IVF”… ….This is true, however aside from the surgical egg retrieval which (when done in the right setting) is a safe procedure, IUI with gonadotropins requires largely the same drugs, preparation and monitoring as does IVF and the success rate is several fold lower than for IVF.
iv. IUI is a viable option when at least one Fallopian tube is patent: Most tubal damage is due to prior pelvic inflammatory disease and this almost always affects both Fallopian tubes. What this means is that when only one tube is damaged or blocked the other (whether patent or not) is almost invariably affected as well. For a viable intrauterine pregnancy to occur following IUI, a healthy intra-tubal environment is an absolute necessity. This serves to explain why the chance of successful pregnancy following IUI is severely compromised in such cases. It also serves to explain why the chance of pregnancy is markedly reduced and why the risk of a tubal (ectopic) gestation is markedly increased in such cases. It is therefore my opinion, that IVF should be considered preferentially when one tube is damaged and this is deemed to be the likely consequence of tubal infection.
v. The chance of a multiple pregnancy can be controlled with IUI: When compared with IVF, IUI has another major disadvantage. This is because in women with ovulation dysfunction (e.g.; those who have irregular or absent menstruation such as with PCOS) ovarian stimulation often results in the release of multiple eggs at a time and it is not possible to limit number of embryos that reach the uterus. This is why when, undergoing IUI, such women are very likely to have multiple pregnancies (triplets or greater) which is associated with serious perinatal and long term complications. It is only through IVF that by regulating the number of embryos transferred to the uterus that the risk of multiple pregnancies can be limited.

In my opinion, we as physicians need to rethink the basis upon which we recommend IUI as an alternative to IVF and educate our patients accordingly.
.
Geoff Sher

reply
Scottie

Dr. Sher,

My clinic informed me that my beta 12dp5dt of 248 was low. I’ve had 2 more beats taken 14dp5dt it went to 694 then 16dp5dt it went to 1518. They have more than doubled but I’m worried that the number is still low. I had to switch from PIO to vaginal suppository because of a allergic reaction on 5dp5dt. Could that have affected anything and caused the lower betas?

Thank you!

Dr. Geoffrey Sher

Frankly, I respectfully differ. I think all is going well and am guardedly optimistic for you.

Geoff Sher

pri586

I had an appointment with my doctor yesterday as we will be doing another round of IUI, she is not recommending IVF as of now as we don’t have any major infertility apart from male factor and my egg reserve count is below average.

She prescribed Femara instead of Clomid. Do you think Femara is better than Clomid?

Dr. Geoffrey Sher

Femara has the edge because unlike clomiphene it is not an anti-estrogen.

Geoff Sher

Victoria K

Dear Dr Sher,

I would love your thoughts on my numbers please. I am 34 and this is 4th pregnancy after one healthy, one chemical and one blighted ovum which happened this Feb.
I have felt ovulation pretty strong on 8th Aug.
On 20th Aug I made a blood test on 4w2d and it showed HCG 69, Progesterone 21.
On 24th Aug 4w 6d HCG – 375, Progesterone 17.5.
I was put on Progesterone 400 mg a day.
On 28th Aug 5w2d HCG – 2383, Progesterone 21.57.

Do you think these are looking good? Shall i continue with 400mg till end of 1st trimester?
Any chance of more than 1 baby with this HCG rise, as my mum made a joke about this..

Thank you!

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Dr. Geoffrey Sher

I ordinarily do not prescribe such high dosages of progesterone…but that is for you and your treating RE to delermine.

I think the numbers are promising and I wish you good luck and G-d speed!

Geoff Sher

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Victoria K

Thank you so much for your response. The doses are such as my doctor thinks levels are too low.
I am keeping my fingers crossed!

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helloworld2020

Hi Dr Sher,

I need some insight on my fertility treatment-

I had done my first iui on 30th March 2020 with clomid and puregon injectibles. And I conceived but miscarried on 24th May as it was a blighted ovum (yolk sac was empty). My doctor asked to take two cycle break before we do second round of iui. Also since mid March, we are taking supplements prescribed by the doctor. I am taking CoQ10, Folic acid, Myoinositol and Nrurozan and my husband is taking Profertil and Motil.

My second iui happened on 13th August with clomid and 75 iu/ml per day. I had two follicles, one on left side and other one on right side. On 11th August both follicle size was 18 mm then I took one more puregon shot on 12th August and I triggered ovidrel in the afternoon. Even my husband’d sperm count was good on the day of insemination.
In TWW, I felt severe leg pain for two days and also I felt nauseous. But my pregnancy test came out as negative on 27th August (hcg is just 1.2). Now my doctor is recommending for third round of iui.

I would like to understand what could have gone wrong or how can we improve our chances in iui. When I ask this question to my doctor she gets away by saying, chances of pregnancy with iui are only 15% to 20%, let’s hope for the best. We eat healthy, no one smokes, I don’t have any fertility issues, I also ovulate naturally and get my periods regularly.

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Himanshu Singh

Hi Dr. Sher,
My wife period started on 13th of July. Her ovulation test was positive on July 27th and we think that conception was on July 28th or July 29th. My wife has a cycle of 30 days. We had a positive pregnancy test on Aug 16th. We had our first ultrasound on July 24th and was able to see the gestational sac. On July 24th we had hcg which can as 4024 and again on July 26th and it came as 5593. The increase was about 40%. Do you think this is concerning? Thanks a lot for your help.

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Dr. Geoffrey Sher

Not necessarily because, as the hCG level gets to around 4000-6000U, it does not rise as rapidly.

Geoff Sher

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Jana

Hi there ,

I had a 5 day frozen embryo transfer on August 12, 2020.

First HCG 8/21 – 9 DPT – 75.95
2nd HCG 8/24 – 12 DPT – 179.17
3rd HCG 8/26 – 14 DPT – 397.89

Are these values low, even thought they seem to be doubling appropriately?

Thanks!

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Dr. Geoffrey Sher

Approximately 1 out of every 100 embryos will implant and grow outside of the uterine cavity (almost always) in a fallopian tube. This is defined as an ectopic pregnancy. Infrequently, an ectopic pregnancy attaches to an ovary or to one or more other pelvic organs. On very rare occasions (1;1,000), one twin attaches and grows in the uterine cavity with the other growing outside the uterus (i.e. a heterotopic pregnancy).
There is an ever present risk that a tubal (ectopic) pregnancy might rupture causing potentially catastrophic internal hemorrhage. Accordingly any symptoms suggesting that such bleeding has started, requires immediate confirmation of the diagnosis followed by emergency treatment.
While on rare occasions, an extrauterine (ectopic) can proceed well into pregnancy, it almost always happens prior to the 8th week. There is an increase in the incidence of ectopic pregnancy after IVF conceptions where it reportedly occurs in about 3% of cases and a woman who has had one ectopic pregnancy has almost four times as great a risk of an ectopic in a future pregnancy. In fact with every subsequent ectopic this risk of a recurrence increases dramatically.

The fertilization of the human egg normally takes place in the fallopian tube. The embryo then travels into the uterus, where it implants into the endometrial lining 5-6 days after ovulation. Anything that delays the passage of the embryo down the fallopian tube can result in the embryo hatching and sending its “root system” into the wall of the fallopian tube and initiating growth within the tube. One of the most common predisposing factors is pelvic inflammatory disease (PID) in which microorganisms, such as Chlamydia, and Gonococcus damage the inner lining (endosalpinx) and eventually also the muscular walls of the tube(s) by the formation of scar tissue. The endosalpinx has a very complex and delicate internal architecture, with small hairs and secretions that help to propel the embryo toward the uterine cavity. Once damaged, this lining can never regenerate. This is one of the reasons why women who manage to conceive following surgery to unblock fallopian tubes damaged by PID, have about a 1:4 chance of a subsequent pregnancy developing within the fallopian tube (ectopic).

Congenital malformations of the fallopian tube, associated with shortening of, or small pockets and side channels within, the tube are capable of interrupting the smooth passage of the embryo down the fallopian tube, is another cause of an ectopic pregnancy.

Since the lining of the fallopian tube does not represent an optimal site for healthy implantation, a large percentage of pregnancies that gain early attachment to its inner lining will usually be absorbed before the woman even knows that she is pregnant. This is often referred to as a tubal abortion.

The advent of advanced sonographic and hormonal monitoring technology now makes it possible to detect an ectopic pregnancy much earlier than previously, …usually well in advance of it rupturing. A decade or two ago, the diagnosis of an ectopic pregnancy, ruptured or not, was an indication for immediate laparotomy to avoid the risk of catastrophic hemorrhagic shock. This often resulted in the affected fallopian tube having to be completely removed, sometimes along with the adjacent ovary. In the late 1980’s, early conservative surgical intervention by laparoscopy began replacing laparotomy (a wide incision made in the abdominal wall) for the treatment of ectopic pregnancy, often allowing the affected fallopian tube to be preserved and shortening the period of post-surgical convalescence. In the 90’s, early detection combined with the advent of medical management with methotrexate (MTX) has all but eliminated the need for surgical intervention in the majority of patients. If administered early enough, MTX will allow spontaneous resorbtion of the pregnancy and a dramatic reduction in the incidence of catastrophic bleeding. This was especially true in ectopic pregnancies arising from In Vitro Fertilization, where the early progress of pregnancy is usually carefully monitored with hormone levels and ultrasound.

Classically women with an ectopic pregnancy present with the following symptoms:

• Missed menstrual period: Although some patients will have spotting or other abnormal bleeding. The pregnancy test will be positive in such cases.

• Vaginal bleeding. When a pregnancy inadvertently implants in the fallopian tube the lining of the uterus undergoes profound hormonal changes associated with pregnancy (primarily associated with the hormone progesterone). When the embryo dies, the lining of the uterus separates. Initially, vaginal bleeding is dark and usually is quite scanty, even less than with a normal menstrual period. In some cases, of ectopic pregnancy will bleeding is more severe, similar to that experienced in association with a miscarriage. This sometimes leads to an ectopic pregnancy initially being misdiagnosed as a miscarriage and is the reason to examine the material that is passed vaginally, for evidence of products of conception.

• Pain. In the early stages this is typically cramp-like in nature, located on one or another side of the lower abdomen. It is caused by spasm of the muscular wall of the fallopian tube(s). When a tubal pregnancy ruptures the woman will usually experience an abrupt onset of severe abdominal followed by light headedness, coldness and clamminess and will often collapse due to shock. Her pulse will become rapid and thready and her blood pressure will drop. Miscarriage. Sometimes the woman will experience pain in the right shoulder. The reason for this is that that blood which tracts along the side of the abdominal cavity finds its way to the area immediately below the diaphragm, above the liver (on the patient’s right side), irritates the endings of the phrenic nerve, which supplies that part of the diaphragm. This results in the referral of the pain to the neck and the right shoulder. The clinical picture is often so typical that making the diagnosis usually presents no difficulty at all. However, with less typical presentations the most important conditions to differentiate from an ectopic pregnancy are: a ruptured ovarian cyst, appendicitis, acute pelvic inflammatory disease (PID), or an inevitable

• Vaginal bleeding. When a pregnancy inadvertently implants in the fallopian tube the lining of the uterus undergoes profound hormonal changes associated with pregnancy (primarily associated with the hormone progesterone). When the embryo dies, the lining of the uterus separates. Initially, vaginal bleeding is dark and usually is quite scanty, even less than with a normal menstrual period. In some cases, of ectopic pregnancy will bleeding is more severe, similar to that experienced in association with a miscarriage. This sometimes leads to ectopic pregnancy initially being misdiagnosis as a miscarriage and is the reason that we often want to examine the material that is passed vaginally, for evidence of products of conception.

The easiest and most common method of diagnosing an ectopic pregnancy is by tracking the rate of rise in the blood levels of hCG. With a normal intrauterine pregnancy, these usually double every two days throughout the first few weeks. While a slow rate of increase in blood hCG usually suggests an impending miscarriage, it might also point to an ectopic pregnancy. Thus the hCG blood levels should be followed serially until a clear pattern emerges.

A vaginal ultrasound examination usually will clinch the diagnosis by showing the ectopic pregnancy within a fallopian tube and if the tube has already ruptured or internal bleeding has occurred, ultrasound examination will inevitably detect the presence of free fluid into the abdominal cavity.

If there has been a significant amount of intra-abdominal bleeding, irritation of the peritoneal membrane will cause the abdominal wall to become hard tense and, depending on the amount of internal bleeding abdominal distention will be evident. Palpation of the abdominal wall will evoke significant pain and when a vaginal examination is done, movement of the cervix will produce excruciating pain, especially on the side of the affected fallopian tube.

Surgical Treatment: In questionable situations laparoscopy is usually performed for diagnostic purposes. If an ectopic pregnancy is in fact detected, a small longitudinal incision over the tubal pregnancy will allow its removal, without necessitating removal of the tube. (linear salpingectomy). Bleeding points on the fallopian tube can usually be accessed directly and appropriately ligated (tied) via the laparoscope. Sometimes the damage to the fallopian tube has been so extensive that the entire tube will require removal.

On occasions where very severe intra-abdominal bleeding heralds a potential catastrophe, a laparotomy (an incision made to open the abdominal cavity) is performed to stop the bleeding post haste. In such cases a blood transfusion is usually required and may be life saving.

Medical Treatment: The introduction of Methotrexate (MTX) therapy for the treatment of ectopic pregnancy has profoundly reduced the need for surgery in most patients. MTX is a chemotherapeutic that kills rapidly dividing cells, such as those present in the “root system” of the conceptus. Extremely low doses of MTX are used to treat ectopic pregnancy. Accordingly the side effects that are often associated with such chemotherapy used for the treatment of other conditions are seldom seen. It is important to confirm that the ectopic pregnancy has not yet ruptured prior to administering MTX.

MTX is given by intramuscular injection. Prior to its administration, blood is drawn to get a baseline blood hCG level. After the injection of MTX the patient is allowed to return home with strict instructions that she should always have someone with her and never be alone in the ensuing week. The concern is that were the patient to be on her own and an intraabdominal bleed were to occur, she might not readily be able to access someone who could get her to the hospital immediately. Instructions are also given to look for early signs that might point towards severe intra-abdominal bleeding such as the sudden onset of severe pain, light-headedness or fainting.

The patient returns to the doctor’s office four days later to check the blood hCG level. Three days later (7 days after MTX), the level is checked again. By this time the hCG level should have dropped at least 15% from the value on day 4. If not, a second MTX injection is given and the blood levels are tested twice weekly until hCG level is undetectable. Once this occurs, vaginal bleeding will usually ensue within a week or two.

It is important to note, especially in cases where more than one embryo or blastocyst has been transferred to the uterine cavity or fallopian tube (as with Tubal embryo transfer –TET/ZIFT), that implantation may occur in two sites simultaneously (i.e. in the fallopian tube as well as inside the uterine cavity). This is referred to as a heterotopic pregnancy. It is therefore important that before administering MTX, which will cause the death and absorption of any early pregnancy, that the physician makes certain that he/she is not dealing with a heterotopic pregnancy. In such cases, surgery is required to treat the tubal ectopic, while every precaution is taken to protect the pregnancy growing within the uterine cavity.

When an ectopic pregnancy occurs following infertility treatment, there is the added advantage that the physician will be on the lookout for the earliest possible signs of trouble. The performance of a vaginal ultrasound within two weeks of a positive blood pregnancy (HCG) test following IVF allows for early detection of the unruptured pregnancy and timely intervention with MTX and/or laparoscopy.

Geoff Sher

reply
Deb

Hi Dr. Sher,
I had an ectopic pregnancy last year. Had laparoscopy, and my tube was not removed.
Exactly one year later I´m pregnant again!! I ovulated on the same side (left) and I am just SO scared of ending with another ectopic… I know that I have a higher risk for another one.

My LMP was on 07/29 (I have 25-26 day cycles)
08/21 –> 1° Beta (10/11 dpo) –> HCG 26
08/25 –> 2° Beta (14/15 dpo) –> HCG over 300
Both times progesterone levels were very good (and I don’t take supplements)
I haven’t had any type of bleeding, or spotting, but have on and off pinching on my left side. I guess this can be normal?

Do you think that there’s still a high chance for it being ectopic? Even with fast doubling HCG and good progesterone values? (last time low and slow increasing HCG + ultra low progesterone values were the bad indicators)

I have an US scheduled for next week (starting week 5) and I understand this will be more conclusive… It’s just that I would like to know if I can relax a little bit, and hope for a good outcome, or if I should still be really aware of ectopic symptoms during this week.

Thanks in advance!

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Dr. Geoffrey Sher

Indeed the chance of another ectopic pregnancy is increased. However, the chance is far greater that this will be a viable intrauterine pregnancy,

Good luck!

Geoff Sher

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Deb

Thank you very much for replying so quickly 🙂
I’m trying to stay positive and not worry… it’s just that having a low start at HCG 26 that four days later increases above 300 (at just barely 4 weeks) seems a high value… or is it a normal increase?
I just can’t stop thinking about the possibility of another ectopic. At these increase rates my tube could burst any moment, right?? I guess I’ll just have to take a deep breath, put my mind on something else, and wait one more week.

reply
Dr. Geoffrey Sher

I do not think you have an alternative. You should be in regular contact with your treating Physician.

Good luck!

Geoff Sher

reply
Deb

Hi Doctor!
Just wanted to say thank you once again, for taking the time to answer everyone’s questions ☺
I had my first scan today, at 5w2d. My HCG values rose above 9000! I can also happily say that the pregnancy is in the Uterus ☺ We saw an intrauterine gestational sac with a yolk (no embryo yet). We will repeat a scan on Sept 11th, where Doctor hopes to see an embryo with a heartbeat.

1st HCG 8/21 – (11 DPO) – 26
2nd HCG 8/25 – (15 DPO) – over 300
3rd HCG 9/2 – (23 DPO) – over 9000

Does this last HCG value (>9000) seem a high one for 5 weeks? We only saw 1 sac and 1 yolk… if it were twins, 2 sacs should have already be seen… right? Would it still be possible to have a hidden ectopic somewhere else ?!! (sorry, ectopic ghost just seems to keep haunting me…)

Thanks!

Dr. Geoffrey Sher

This is likely to be a healthy singleton IUP.

Congratulations and good luck!

Geoff Sher

Irina

Cher Dr Sher,

J’ai eu un insemination artificiel le 2 août. Le 24 août, mon taux de HCG était de 459 et n’a augmenté que de 59% après 48 heures. Dois-je m’inquiéter, est-ce que cela pourrait encore être une grossesse viable?

Merci beaucoup

reply
Irina

Dear Dr. Sher,

I had an IUI on August,2. On August, 24 my beta HcG total was 459. After 48hours, on August,26 I retested and it has only increased by 59%, to 730UI/L. The date of my last period is July, 19th. Should I worry? Can it be a viable pregnancy? This should be my first baby.

Thank you so much for taking time to answer to all the questions you receive. You bring so much joy and comfort to your followers.

reply
Dr. Geoffrey Sher

Irina,

It is possible that this could still be a viable pregnancy. However, with the slowish rise in hCG there is some concern. I would wait until the 7th week of pregnancy and do an US for definitive confirmation.

Geoff Sher

reply
rina

Today is 2 weeks after IVF embryo transferred and doctor confirm my beta hcg is 2 and i am not pregnant, due to low reading .Probably menstrual may come after a week from today. i am so sad and never stop crying.

reply
Dr. Geoffrey Sher

So sorry!

Perhaps we should have an online consultation. Call Patti (702-533-2691 if you wish to set this up!

Geoff Sher

reply
Andrea H.

I am so grateful that you take the time to respond to concerns. I had an iui on 8/10, I had 4 mature follicles. I had my 14day beta yesterday and it was 177. The nurse said “congratulations but we need to see if it’s going to double.” I have two other children, and I’ve never been required to do this. Is this number abnormally low for 14dpiui? I am trying not to feel panicked. Thank you so much.

reply
Dekesha Thomas

I had a miscarriage on July 27 my hcg was at 1600….. I went back to the docotor on the aug3 and it drop to 876 I went back to the docotor on aug 10 and it was 176 hcg…… I went back to the doctor on 17 and it was 60.7 hcg…. but I been having sex that one week after my miscarriage…. I got back on tomorrow to get my hcg level check again…. is it possible i might be pregnant but can’t detect yet it my hcg level drop to zero?

reply
Dr. Geoffrey Sher

I doubt strongly that you are pregnant. The level should continue to drop.

Good luck!

Geoff Sher

reply
Sana Noormohamed

Hi doctor, its been 8 weeks since my last menstrual cycle. Urine pregnancy test all came negative, i did a blood test yesterday which was positive but hcg was 26 what could this mean? So worried…

reply
Dr. Geoffrey Sher

Perhaps you ovulated and conceived late…after skipping a period. I suggest you repeat the test in 2 days to see of it doubles.

Good luck!

Geoff Sher

reply
sadia ejaz

Thank you for the useful information.
I had miscarriage in last cycle at 5 weeks and i conceived again.
According to LMP my 6 weeks HCG was 968, HCG after 72 hours 3700.
I am having dark brown spotting for 3 days. I am worried about another miscarriage. Please advise.

reply
Dr. Geoffrey Sher

I would not worry too much. As long as the bleeding does not escalate and there is no severe cramping….

Vaginal bleeding occurs in about 25% of all pregnancies. When it happens, it almost invariably raises the concern of pregnancy loss (miscarriage). Bleeding can also be a sign of a tubal (ectopic) pregnancy, and in cases where the distended Fallopian tube ruptures it can precipitate a life-threatening crises. However, a small amount of painless vaginal bleeding can also be the result of normal embryo implantation (i.e. implantation bleeding) or it can result a local erosion of the vagina or cervix and/or trauma during intercourse.

Geoff Sher

reply
bianca

8/11 HCG 35.5
8/15 HCG 108
8/21 HCG 3000/ u/s read 3 to 4 weeks pregnant could not really see much ive had irregular mp so im not sure of lmp at all
could I possibly be having multiples?

reply
Dr. Geoffrey Sher

Itcould be >1 but it is still too early. Repeat US in 2 weeks…..

Geoff Sher

reply
bianca lesueur

sorry i just looked at the paper work it was actually 3767.8 not 3000 but I do have a family history i can wait to see.
So these are promising numbers of twins right?

reply
KJ

Hi Doctor,

My wife had a Frozen Embryo transfer yesterday. This is our 3rd attempt — first two times the embryo failed to implant, since she is 32 and we have no known fertility issues they said this time we will be adding 250 mg Ovidrel booster (not sure of the dosage but its 5 clicks) every other day until the 29th. Her blood test is scheduled for September 4th. I’m worried about getting a false positive. Is that enough time between Aug. 29th and Sept. 4th for a positive result to be definite and not a result of the ovidrel? Thanks for your help.

reply
Dr. Geoffrey Sher

I share your concern of a falser-+ve hCG test!

Ideally there should be >10 dys between the hCG shot and testing.

Geoff Sher

reply
Amy

Hi, I had 2 precious chemical pregnancies and am now pregnant, 4 weeks 5 days, and under the care of a fertility doctor. According to what I see online my hcg is slightly higher than it should be but they’re aging the numbers look great. Again, I’m only 4 weeks 5 days. Do these numbers look unusually high to you for that stage?
8/11: 97
8/13: 218
8/17: 1167
8/19: 2703

reply
kaleen Boyd

Hello Dr Sher,
I had a fresh transfer of 2 embryos but unfortunately at 8 weeks still only showing 2 empty sacs measuring a week behind and had a D&C done and pending karyotype/genetic testing. I have hypothyroidism and prolactinoma but both stable. I am on Synthroid and Dostinex to treat both disorders. I was tested negative for autoimmune disease. I have 2 fibroids but before transfer they are very small none was inside cavity to affect growth of embryo. I have had 6 miscarriages, both chemical and blighted ovums. Past genetic testings after 2 previous D&Cs have shown normal genetic material. I feel its an immune issue that is affecting me. I did take methylprednisone 16 mg, only for 6 days before transfer but wondering If I need to stay on it longer?
Do you think patients with thyroid problems have a better outcome with embryo transfer with longer treatment of steroids?
Also my TSH always jumps when i takes estrogen to prepare lining for a FET, what do you suggest to prevent this happening?
Thank you

reply
Dr. Geoffrey Sher

Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID) Why did my IVF Fail
• Recurrent Pregnancy Loss (RPL): Why do I keep losing my Pregnancies
• Genetically Testing Embryos for IVF
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in several Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF

______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

PLEASE SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Kaleen

Thank you Dr Sher. Just to understand a little better, so even though I may not have evidence of thyroid antibodies, I could still have activated uterine natural killer cells? Is there a special test to know if I have these activated natural killer cells?
Thank you

reply
Dr. Geoffrey Sher

Unless tests for immunologic implantation dysfunction (IID) are performed correctly and conducted by a one of the few reliable reproductive immunology reference laboratory in the United States, treatment will likely be unsuccessful. . In this regard it is most important that the right tests be ordered and that these be performed by a competent laboratory. There are in my opinion only a handful of reliable Reproductive Immunology Laboratories in the world and most are in the U.S.A. Also, it is my opinion that far too often, testing is inappropriate with the many redundant and incorrect tests being requested from and conducted by suboptimal laboratories. Finally for treatment to have the best chance of being successful, it is vital that the underlying type of IID (autoimmune IID versus alloimmune) be identified correctly and that the type, dosage, concentration and timing of treatments be carefully devised and implemented. I recommend that my patients be tested by ReproSource Reproductive Immunology Reference Laboratory, Boston, MA.
WHO SHOULD UNDERGO IID TESTING?
When it comes to who should be evaluated, the following conditions should in always raise a suspicion of an underlying IID, and trigger prompt testing:
• A diagnosis of endometriosis or the existence of symptoms suggestive of endometriosis (heavy/painful menstruation and pain with ovulation or with deep penetration during intercourse) I would however emphasize that a definitive diagnosis of endometriosis requires visualization of the lesions at laparoscopy or laparotomy)
• A personal or family history of autoimmune disease such as hyper/hypothyroidism (as those with elevated or depressed TSH blood levels, regardless of thyroid hormonal dysfunction), Lupus erythematosus, Rheumatoid arthritis, dermatomyositis, scleroderma etc.)
• “Unexplained” infertility
• Recurrent pregnancy loss (RPL)
• A history of having miscarried a conceptus that, upon testing of products of conception, was found to have a normal numerical chromosomal configuration (euploid).
• Unexplained IVF failure
• “Unexplained” intrauterine growth retardation due to placental insufficiency or late pregnancy loss of a chromosomally normal baby
What Parameters should be tested?
In my opinion, too many Reproductive Immunologists unnecessarily unload a barrage of costly IID tests on unsuspecting patients. In most cases the initial test should be for NK cell activation, and only if this is positive, is it necessary to expand the testing.
The parameters that require measurement include:
o For Autoimmune Implantation Dysfunction: Autoimmune implantation dysfunction, most commonly presents with presumed “infertility” due to such early pregnancy losses that the woman did not even know she was pregnant in the first place. Sometimes there as an early miscarriage. Tests required are: a) blood levels of all IgA, IgG and IgM-related antiphospholipid antibodies (APA’s) directed against six or seven specific phospholipids, b) both antithyroid antibodies (antithyroid and antimicrosomal antibodies), c) a comprehensive reproductive immunophenotype (RIP) and, c) most importantly, assessment of Natural Killer (NK) cell activity (rather than concentration) by measuring by their killing, using the K-562 target cell test and/or uterine cytokine measurement. As far as the ideal environment for performing such tests, it is important to recognize that currently there are only about 5 or 6, Reproductive Immunology Reference Laboratories in the U.S capable of reliably analyzing the required elements with a sufficient degree of sensitivity and specificity (in my opinion).
o For Alloimmune implantation Dysfunction: While alloimmune Implantation usually presents with a history of unexplained (usually repeated) miscarriages or secondary infertility (where the woman conceived initially and thereupon was either unable to conceive started having repeated miscarriages it can also present as “presumed” primary infertility. Alloimmune dysfunction is diagnosed by testing the blood of both the male and female partners for matching DQ alpha genes and NK/CTL activation. It is important to note that any DQ alpha match (partial or complete) will only result in IID when there is concomitant NK/CTL activation (see elsewhere on this blog).

How should results be interpreted?
Central to making a diagnosis of an immunologic implantation dysfunction is the appropriate interpretation of natural killer cell activity (NKa) .In this regard, one of the commonest and most serious errors, is to regard the blood concentration of natural killer cells as being significant. Rather it is the activity (toxicity) of NK cells that matters as mentioned. Then there is the interpretation of reported results. The most important consideration is the percentage of target cells “killed” in the “native state”. In most cases a level of >10% killing should be regarded with suspicion and >12% overtly abnormal. In my opinion, trying to interpret the effect of adding IVIG or Intralipid to the sample in order assess whether and to what degree the use of these products would have a therapeutic benefit is seriously flawed and of little benefit. Clinically relevant NK cell deactivation can only be significantly effected in vivo and takes more than a week following infusion to occur. Thus what happens in the laboratory by adding these products to the sample prior to K-562 target cell testing is in my opinion likely irrelevant.
There exists a pervasive but blatant misconception on the part of many, that the addition of Intralipid (IL) /immunoglobulin-G IVIG) can have an immediate down-regulatory effect on NK cell activity. This has established a demand that Reproductive Immunology Reference Laboratories report on NK cell activity before and following exposure to IVIG and/or IL. However, the fact is that activated “functional” NK cells (NKa) cannot be deactivated in the laboratory. Effective down-regulation of activated NK cells can only be adequately accomplished if their activated “progenitor/parental” NK cells are first down-regulated. Thereupon once these down-regulated “precursor” NK cells are exposed to progesterone, they will begin spawning normal and functional NK cells, which takes about 10-14 days. It follows that to assess for a therapeutic response to IVIG/IL therapy would require that the patient first be treated (10-14 days prior to embryo transfer) and thereupon, about 2 weeks later, be retested. While at 1st glance this might seem to be a reasonable approach, in reality it would be of little clinical benefit because even if blood were to be drawn 10 -14 days after IL/IVIG treatment it would require an additional 10 days to receive results from the laboratory, by which time it would be far too late to be of practical advantage.

Neither IVIG nor IL is capable of significantly suppressing already activated “functional NK cells”. For this to happen, the IL/IVIG would have to down-regulate progenitor (parent) NK cell” activity. Thus, it should be infused 10-14 several prior to ovulation or progesterone administration so that the down-regulated “progenitor/precursor” NK cells” can propagate a sufficient number of normally regulated “functional NK cell” to be present at the implantation site 7 days later. In addition, to be effective, IL/IVIG therapy needs to be combined with steroid (dexamethasone/prednisone/prednisolone) therapy to down-regulates (often) concomitantly activated T-cells.
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID) Why did my IVF Fail
• Recurrent Pregnancy Loss (RPL): Why do I keep losing my PregnanciesGenetically Testing Embryos for IVF
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF

___________________________________________________________
ADDENDUM: PLEASE READ!!
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

PLEASE SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Vee

Based off my LMP I’m about 5wks1d and lastnight in the ER my levels came back at 3308.4. I have a complicated History and recurrent miscarriages is that a good number or should I be worried? An how accurate is the weeks based off LMP could it be off ?

reply
Dr. Geoffrey Sher

So an US in 1-2 weeks to track growth and development!

Hopefully all will be well!@

Geoff Sher

reply
Lisa Whiting

5day FET Transfer (PGS Tested) – 1 embryo transferred
8dp5dt = 21.3
10dp5dt = 38.3 (Progesterone 27)
14dpfdt = 227.5 (progesterone 17)
I’m going for a fourth beta in 4 days. Any worry on Progesterone decline? Currently taking 2ml of PIO daily. They made a mistake ordering the Progesterone test twice, they normally only test once and move forward. HCG started out low but seems to be progressing nicely.

reply
Dr. Geoffrey Sher

I think you have reason to be guardedly optimistic!

Good luck and G-d bless!

Geoff Sher

reply
Elizabeth Miller

I had an HcG of 166 (8/4) at 17 DPO that increased to 437 (8/7) at 20 DPO but the increase slowed and it was only 929 (8/11) at 24 DPO. My progesterone was 19.1 5 DPO (testing whether I ovulated) and dropped to 10.9 (8/4) , and only increased to 11.2 (8/11) with progesterone suppositories. At 5 weeks 5 days, I had a transvaginal ultrasound and only a gestational sac was seen. This seems suggestive of an anembryonic pregnancy?

reply
Dr. Geoffrey Sher

This could be a problem Repeat the hCG 2 days later it should be around 2,000.

Good luck !

Geoff Sher

reply
AB

My wife had IUI on 7/24 and had positive blood test today (8/14). So she is 3 weeks post IUI but HcG levels are only 20… seems extremely low. Should we be worried? She goes in Tuesday for another blood test.

reply
Dr. Geoffrey Sher

Do another blood test 2 days after the 1st. It should double or better. Ultimately, an US done at6-7 weeks will be definitive.

Good luck!

Geoff sher

reply
HS

My HCG levels a week apart:
Week 3 – 41.75
Week 4 – 309
Week 5 – 4061 * US showed a sac
Week 6 – 4103 * US showed a sac with thicker lining but no heartbeat yet
Next Ultrasound for 8/18

Should I be worried that my HCG didn’t double in a week and no heartbeat yet on the Ultrasound? My Doctor does think that my implantation must have been late.

reply
Dr. Geoffrey Sher

I would wait for the next US in 1 week…which should be definitive.

Geoff Sher

reply
Emily

Hi Dr. Sher,

At 3.3 DPIUI my hcg was 547. At 3.5 DPIUI it almost tripled to 1481. I’ve been doing lots of online reading and it seems that my hcg are higher than some who conceived twins. It also seems to be in line with the median numbers for triplets. What are your thoughts? Im 4 weeks tomorrow ad wont have an ultrasound until week 7.

reply
Niamh

Hi Dr
I took 5000IU trigger shot Mon 3rd Aug and had my IUI on Wed 5th Aug, its now 6DPIUI. How long does it take for the HCG from the trigger shot to leave the system? Don’t want to test too early incase the positive pregnancy test could just be the trigger shot and not a real pregnancy.

reply
Linda

Hello Dr.,

I was on femara, got a trigger shot and did IUI. 14DPIUI my hcg was 547. At 16 DPIUI, it was 1481. Does this indicate possible twins or a normal trend?

reply
Chelsey mensen

So I had hcg levels tested the first one was 1992 the second 2739 they are concerned it didnt double the first test I took was exactly 5 weeks from the beginning of my lmp is this a good number or should I be concerned

reply
Dr. Geoffrey Sher

Chelsey, frankly I think this could still be OK. However, you need an US examination to determine viability!

Geoff Sher

reply
Sloan C

At 8/4 6W3D hcg was 31,557 And progesterone was 9.90 then 8/6 6W5D hcg 27,000 progesterone 23.05 my doctor said it going doing can be normal once it hits a certain level is that true?

reply
Abbie

Hi Dr.
I wanted to understand around high HCG levels and when to be concerned. I did my first test 04/08 and this came back 14,885 I am just over 5 weeks pregnant. 48 hours later 06.08 these came in at 28,646 (5.5 weeks pregnant.
I understand that these are currently in the normal range but given they are doubling high so quickly this will put me quickly out of this range.
I had a EP scan today and indicated only 1 x baby and there was a heart beat so not molar pregnancy.
Would I need to worry about Down Syndrome at this level as I am 35 yo.
Thanks
Abbie

reply
Gabriela

I am about 4 weeks pregnant my results came back today and I was 180 HCG and 8.5 in progesterone. Should I be worried?

reply
Dr. Geoffrey Sher

Repeat in 2 days. It should double. Then ultimately an US done at 6-7 weeks will be definitive!

Geoff sher

reply
Caycee

Hello! I had my period July 17-22. I had taken pregnancy tests the whole week before this. They were all negative. Was with my husband July 26th and 28th, and Aug 1. Started spotting with very small clots on August 3rd. Took 2 at home pregnancy tests on the 3rd, both immediately positive. Had a blood draw on the 4th, level was 183. I’ll go back in 3 days for another. And then at a week from the first. Should I be worried about ectopic, molar, or chemical at this point? Not sure how it’s even possible for me to be pregnant right now, or what an hcg level would be for a 28 day cycle when I guess I’m not even 3 weeks along yet. Thank you so much for sharing your knowledge!!!

reply
Dr. Geoffrey Sher

The serial levels of hCG will give an indication as to whether this is a viable pregnancy. Thereupon it will be an US done at 6-7 weeks that would provide a definitive indication.

Geoff Sher

reply
Ashley

Hi Dr. Sher,
I need some insight. I went for my first HCG test on Thursday (5weeks) and my levels were about 4500 and my progesterone was 8.5 so they put me on vaginal progesterone supplements that same night. I went back Monday (5wks4days) and my HCG is only about 4650. Is there any hope? I’ll be going for an ultrasound soon but I’m worried.

reply
Dr. Geoffrey Sher

The US will offer more information. Unfortunately you must wait for that result.

Good luck!

Geoff Sher

reply
Ree

Hello Dr Geoff,

We had an IUI on 07/12 . On 7/27 my HCG level was 8. On 7/29, two days later is was 10. I was told to stop my progesterone. I got a period on 7/31. I went back on 8/2 and my HCG level was 50. I went back again today and my ultrasound showed nothing (in the tubes, ovaries, or uterus) and my level was 100. I am going back again on Thursday. I do not want to make a premature decision of terminating if there is a chance of a viable pregnancy. Any thoughts?

reply
Dr. Geoffrey Sher

I would repeat the hCG in 2 days to see if it doubles. If so, wait 2 weeks and do an ultrasound for definitive determination.

Geoff Sher

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Lexi

I had an FET of a 4AA embryo and just got my hcg result of 15 at 10dp5dt. Is this a chemical pregnancy?

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Dr. Geoffrey Sher

Youn would need to repeat the test in 2 days to see if it doubles!

Geoff Sher

reply
Kerri

Hi, last month I got pregnant and then miscarried on 7/1/20. on 7/27 I took a urine pregnancy test and it was a faint line positive. Called my doctor, she had me come in for bloodwork. 7/28 my HCG was 21. on 7/30 they repeated the test and my HCG was only 23. They said it was most likely not viable. Later that day on 7/30 I had the faintest of spotting (pink) at one point in the day, never saw it again and haven’t had any bleeding since. Today, 8/3 they repeated the bloodwork for the third time expecting the numbers to decrease, but HCG increased to 106. They said it still is not viable because numbers are not doubling every 2 days. Thoughts? Is last months miscarriage impacting any hormones? Is this for sure a non viable pregnancy? IS it possible for numbers to not increase rapidly at first and still have a healthy baby? Is there any way the slight spotting I saw on 7/30 was actually implantation bleeding?

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Dr. Geoffrey Sher

Hi Kerri,

This does not look very promising but no one can predict what is to happen, with certainty.

I suggest you repeat the hCG blood test in 4 days to see how it changes and then do an US about 2 weeks from now for a definitive determination.

Good luck!

Geoff Sher

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Maria lopez

Hi, I went to do a blood pregnancy test and my HCG came out to 266. Does that mean I’m pregnant??

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Dr. Geoffrey Sher

It says something is implanting. Repeat it in 2 days… If things are on the right path it should double. Thereupon an US ie 10-14 days later should be definitive!

Good luck and G-d bless!

Geoff Sher

reply
Sara

Hello,
I did IVF with PGT-A. Standard transfer timing was confirmed with ERA. A single euploid 5-day embryo was transferred on 06/25/2020. My HCG levels were 18 at 5DPT, 349 at 11 DPT and 656 at 13 DPT. US at 5 + 5 showed gestational sac and yolk sac. At 6+5, embryo was only measuring 6+1 and heart beat was only 87. Doctor was concerned. At 7+5, embryo was only measuring about 6+3 and still had a slow heart rate. My HCG came back at 9140 (at 7+5). Our reproductive endocrinologist told me to stop all meds and allow for miscarriage. Another doctor (obgyn who was going to take over pregnancy) recommends waiting to check another beta HCG in 48 hours. I’m in agony and don’t have much hope but certainly don’t want to give up prematurely. It’s my first pregnancy. I’m 37 and my husband is 47. What are your thoughts? Thank you very much in advance.

reply
Dr. Geoffrey Sher

I would wait 1 more week and repeat the US before taking definitive action!

Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about 15y ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.

4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:

a. A“ thin uterine lining”
b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
c. Immunologic implantation dysfunction (IID)
d. Endocrine/molecular endometrial receptivity issues
e. Ureaplasma Urealyticum (UU) Infection of cervical mucous and the endometrial lining of the uterus, can sometimes present as unexplained early pregnancy loss or unexplained failure following intrauterine insemination or IVF. The infection can also occur in the man, (prostatitis) and thus can go back and forth between partners, with sexual intercourse. This is the reason why both partners must be tested and if positive, should be treated contemporaneously.
Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• The Fundamental Requirements for Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Blastocyst Embryo Transfers should be the Standard of Care in IVF
• IVF: How Many Attempts should be considered before Stopping?
• “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
• IVF Failure and Implantation Dysfunction:
• The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
• Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
• Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
• Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
• Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Endometrial Thickness, Uterine Pathology and Immunologic Factors
• Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF?
______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

PLEASE SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Lisa

Hi Dr. Sher, I am 37 yo and had one 6 day blast FET on July 1st and beta results on July 10th was 41, on July 14th it was 322 and 3600 on July 20th. US was just done on July 27th which is 6 wk 4 days and the doc said he saw 2 gestational sacs and yolk sac but no fetal pole or heartbeat. We are going back on August 6th for a second US. We are terrified and not sure what to think of this and not sure if they will see the fetus pole or heartbeat next week. I am not having any morning sickness or symptoms which I used to experience 8 days ago, just feel little tightness around the belly once in a while. I would really appreciate if you can give your profession advice. Right now I am just crossing my fingers and hoping I get to hear something positive but it is looking bleak.

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Dr. Geoffrey Sher

In my opinion, a repeat US in 1 week will be more definitive. Until then, just try to hang in there.

Good luck and G-d bless!

Geoff Sher

reply
Lisa

Hello Dr Sher, I went back for US (week 8) today and there were still 2 sacs with no fetal pole. As you know this was day 7 frozen blast transfer( 4CC grade). This was my second IVF, both times the embryos were slow developing and day 5 transfers were just early stage blasts. I would need your advice, what can I do to improve the egg quality for the future cycles and hopefully get to viable pregnancy. For this last cycle, I have been on 200mg COQ10 bid and DHEA 25mg tid. I am 37 yo, and would like to see if there is anything else you can recommend that can boost my chances? Thank you so much for all you do to help.

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Dr. Geoffrey Sher

In my opinion, day-7 blastocysts VERY RARELY produce viable pregnancies. It is all about the protocol used for ovarian stimulation.

The importance of the IVF stimulation protocol on egg/embryo quality cannot be overstated. This factor seems often to be overlooked or discounted by t IVF practitioners who use a “one-size-fits-all” approach to ovarian stimulation. My experience is that the use of individualized/customized COS protocols can greatly improve IVF outcome. While no one can influence underlying genetics or turn back the clock on a woman’s age, any competent IVF specialist should be able to tailor the protocol for COS to meet the individual needs of the patient.
Gonadotropins (LH and FSH), whether produced by the pituitary gland or administered by way of fertility drugs, have different “targeted” sites of action in the ovary. FSH targets cells that line the inner wall of the follicle (granulosa cells) and also form the cumulus cells that bind the egg to the inner surface of the follicle. Granulosa cells are responsible for estrogen production.
LH, on the other hand, targets the ovarian connective tissue (stroma/theca) that surrounds ovarian follicles resulting in the production of male hormones such as testosterone (predominantly), androstenedione and DHEA. These androgens are then transported to the granulosa cells of the adjacent follicles in a “bucket brigade fashion”. There FSH converts testosterone to estradiol, causing granulosa cells to multiply (proliferate) and produce estradiol, follicles to grows and eggs to develop (ovogenesis) It follows that ovarian androgens (mainly testosterone) is absolutely indispensable to follicle/ egg growth and development.
However, the emphasis is on a “normal” amount of testosterone. Over-exposure of the follicle to testosterone can in my opinion, compromise egg development and lead to an increased likelihood of chromosomal irregularities (aneuploid) following LH/hCG-induced egg maturational division (meiosis) and compromise embryo “competency/quality.
Ovarian androgens can also reach the uterine lining where they sometimes will compromise estrogen receptor -induced endometrial growth and development.
A significant percentage of older women and those who have diminished ovarian reserve (DOR) have increased LH activity is increased. Such women either over-produce LH and/or the LH produced is far more biologically active. Chronically increased LH activity leads to overgrowth of ovarian connective tissue (stroma/theca). This condition, which is often referred to as Stromal Hyperplasia or hyperthecosis can result in excessive ovarian androgen/testosterone production and poorer egg-embryo quality/competency, Similarly, women with polycystic ovarian syndrome (PCOS), also characteristically have Stromal hyperplasia/hyperthecosis due to chronically increased LH activity. Thus they too often manifest with increased ovarian androgen production. It is therefore not surprising that “poor egg/embryo quality” is often also a feature of PCOS.
In my opinion, the over-administration of LH-containing menotropins such as Menopur, [which is comprised of roughly equal amount of FSH and hCG ,which acts similar to LH)], to older women, women with DOR and those who have PCOS can also lead to reduced egg/embryo competency . Similarly, drugs such as clomiphene or Letrozole that cause the pituitary gland to release excessive amounts of LH, are also potentially harmful to egg development and in my opinion, are best omitted from IVF COS protocols. This is especially the case when it comes to older women and those with DOR, who in my opinion should preferably be stimulated using FSH-dominant products such as Follistim, Puregon, Fostimon and Gonal-F.
Gonadotropin releasing hormone agonists (GnRHa): GnRHa such as Lupron, Buserelin, Superfact, Gonopeptyl etc. are often used to launch ovarian stimulation cycles. They act by causing an initial outpouring followed by a depletion of pituitary gonadotropins. This results in LH levels falling to low concentrations, within 4-7 days, thereby establishing a relatively “LH-free environment”. When GnRHa are administered for about 7 days prior to initiating gonadotropin stimulation (“long” pituitary down-regulation”), the LH depletion that will exist when COS is initiated, will usually be protective of subsequent egg development. In contrast, when the GnRHa administration commences along with the initiation of gonadotropin therapy, there will be a resultant immediate surge in the release of pituitary LH with the potential to increase ovarian testosterone to egg-compromising levels , from the outset of COS. This, in my opinion could be particularly harmful when undertaken in older women and those who have DOR.
GnRH-antagonists such as Ganirelix, Cetrotide and Orgalutron, on the other hand, act very rapidly (within hours) to block pituitary LH release. The purpose in using GnRH antagonists is to prevent the release of LH during COS. In contrast, the LH-lowering effect of GnRH agonists develops over a number of days.
GnRH antagonists are traditionally given, starting after 5th -7th day of gonadotropin stimulation. However, when this is done in older women and those (regardless of age) who have DOR, LH-suppression might be reached too late to prevent the deleterious effect of excessive ovarian androgen production on egg development in the early stage of ovarian stimulation. This is why, it is my preference to administer GnRH-antagonists, starting at the initiation of gonadotropin administration.
My preferred Protocols for Controlled Ovarian Stimulation (COS):
1. “Long” GnRHa (Lupron/Buserelin/Superfact/Gonopeptyl) Pituitary Down-regulation Protocol: The most commonly prescribed protocol for GnRHa/gonadotropin administration is the so-called “long protocol”. Here, GnRHa is given, starting a week or so prior to menstruation. This results in an initial rise in FSH and LH , which is rapidly followed by a precipitous fall to near zero. It is followed by a withdrawal bleed (menstruation), whereupon gonadotropin treatment should commence, while daily Lupron injections continue, to ensure a “low LH” environment. A modification to the “long protocol” which I prefer prescribing for older women and in cases of DOR, is the Agonist/Antagonist Conversion Protocol (A/ACP) where, upon the onset of a GnRHa-induced bleed, the agonist is supplanted by an antagonist (Ganirelix/Cetrotide/Orgalutron) and this is continued until the hCG trigger. In many such cases I often supplement with human growth hormone (HGH) in such cases in an attempt to enhance egg mitochondrial activity and so enhance egg development. This approach is often augmented with preimplantation genetic screening (PGS) of all embryos that reach the expanded blastocyst stage of development by day 5-6 post-fertilization. I also commonly recommend blastocyst banking to many such patients.
2. Short (“Flare”) GnRHa Protocol: Another GnRHa usage for COS is the so called “(micro) flare protocol”. This involves initiating gonadotropin therapy commensurate with initiation of gonadotropin administration. The supposed objective is to deliberately allow Lupron to elicit an initial surge (“flare”) in pituitary FSH release in order to augment FSH administration by increased FSH production. Unfortunately, this “spring board effect” constitutes “a double-edged sword”. While it indeed increases the release of FSH, it at the same time causes a surge in LH release. The latter can evoke excessive ovarian stromal/thecal androgen production which could potentially compromise egg quality, especially when it comes to older women and women with DOR. I am of the opinion that by evoking an exaggerated ovarian androgen response, such “(micro) flare protocols” can harm egg/embryo quality and reduce IVF success rates, especially when it comes to COS in older women, and in women with diminished ovarian reserve. Accordingly, I do not prescribe such protocols to my IVF patients.
3. Estrogen Priming – This is the approach I sometimes prescribe for my patients who have virtually depleted ovarian reserve , as determined by very low blood anti-Mullerian hormone AMH levels (<0.2ng/ml or 2 pmol/L) and are thus likely to be very “poor responders”. It involves a modified A/ACP. We start with estrogen skin patches applied every 2nd day (or with the BCP) for 10 days or longer, overlap it for 3 days with a GnRHa whereupon the estrogen priming is stopped. Th GnRHa is continued until the onset of menstruation (usually 5-7 days later) to cause pituitary LH, down-regulation. Upon menstruation and confirmation by ultrasound and measurement of blood estradiol levels that adequate ovarian suppression has been achieved, The patient is given twice-weekly injections of estradiol valerate (Delestrogen) for a period of 7-8 days whereupon COS is initiated using a relatively high dosage FSH-(Follistim, Fostimon, Puregon or Gonal F), which is continued along with daily administration of GnRH antagonist until the “hCG “trigger.” This approach is often augmented with HGH administration throughout the process of COS and by preimplantation genetic screening (PGS) of all embryos that reach the expanded blastocyst stage of development by day 5-6 post-fertilization. I also commonly recommend blastocyst banking to many such patients.
Estrogen Priming has succeeded in significantly enhancing ovarian response to gonadotropins in many of otherwise very poor responders.
Triggering egg Maturation prior to egg Retrieval: hCG versus GnRHa
With ovulation induction using fertility drugs, the administration of 10,000U hCGu (Pregnyl; Profasi, Novarel) or 500mcg hCGr (Ovidrel/Ovitrel) “trigger”) sends the eggs (into maturational division (meiosis). This process is designed to halve the chromosome number, resulting in mature eggs (M2) that will have 23 chromosomes rather that the 46 chromosomes they had prior to the “trigger”. Such a chromosomally numerically normal (euploid), mature (MII) eggs, upon being fertilized will (hopefully) propagate euploid embryos that have 46 chromosomes and will be “: competent” to propagate viable pregnancies. In my opinion, the key is to always “trigger” with no less than 10,000U of hCGu or 500mcg hCGr (Ovidrel/Ovitrel). Any lesser dosage often will reduce the efficiency of meiosis and increase the risk of the eggs being aneuploid. I personally do not use the agonist (Lupron) “trigger”, unless it is combined with (low dosage) hCG. The supposed reason for using the agonist, (Lupron) “trigger” is that by inducing meiosis through compelling a surge in the release of LH by the pituitary gland, the risk it reduces the risk of OHSS. This may be true, but it comes at the expense of egg quality because the extent of the induced LH surge varies and if too little LH is released, meiosis can be compromised, thereby increasing the likelihood of aneuploid and immature (MI) eggs. And there are other better approaches to preventing OHSS (e.g. “prolonged coasting”), in my opinion.
Use of the Birth Control Pill (BCP) to launch IVF-COS.
In natural (unstimulated) as well as in cycles stimulated with fertility drugs, the ability of follicles to properly respond to FSH stimulation is dependent on their having developed FSH-responsive receptors. Pre-antral follicles (PAF) do not have such primed FSH receptors and thus cannot respond properly to FSH stimulation with gonadotropins. The acquisition of FSH receptor responsivity requires that the pre-antral follicles be exposed to FSH, for a number of days (5-7) during which time they attain “FSH-responsivity” and are now known as antral follicles (AF). These AF’s are now able to respond properly to stimulation with administered FSH-gonadotropins. In regular menstrual cycles, the rising FSH output from the pituitary gland insures that PAFs convert tor AF’s. The BCP (as well as prolonged administration of estrogen/progesterone) suppresses FSH. This suppression needs to be countered by artificially causing blood FSH levels to rise in order to cause PAF to AF conversion prior to COS commencing, otherwise pre-antral-to –antral follicle conversion will not take place in an orderly fashion, the duration of ovarian stimulation will be prolonged and both follicle and egg development may be compromised. GnRH agonists cause an immediate surge in release of FSH by the pituitary gland thus causing conversion from PAF to SAF. This is why women who take a BCP to launch a cycle of COS need to have an overlap of the BCP with an agonist. By overlapping the BCP with an agonist for a few days prior to menstruation the early recruited follicles are able to complete their developmental drive to the AF stage and as such, be ready to respond appropriately to optimal ovarian stimulation. Using this approach, the timing of the initiation of the IVF treatment cycle can readily and safely be regulated and controlled by varying the length of time that the woman is on the BCP.
Since optimizing follicular response to COS requires that prior to stimulation with gonadotropins, FSH-induced conversion from PAF to AF’s first be completed and the BCP suppresses FSH, it follows when it comes to women launching COS coming off a BCP something needs to be done to cause a rise in FSH for 5-7 days prior to menstruation heralding the cycle of CO S. This is where overlapping the BCP with a GnRHa comes in. The agonist causes FSH to be released by the pituitary gland and if overlapped with the BCP for several days and this will (within 2-5 days) facilitate PAF to AF conversion…. in time to start COS with the onset of menstruation. Initiating ovarian stimulation in women taking a BCP, without doing this is suboptimal.
I strongly recommend that you visit www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
• The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
• Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
• The Fundamental Requirements For Achieving Optimal IVF Success
• Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
• Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
• The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
• A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
• Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
• Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
• Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
• Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
• Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
• Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
• Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
• The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
• Staggered IVF
• Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
• Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
• Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
• Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
• IVF: Selecting the Best Quality Embryos to Transfer
• Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
• PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
• PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
• IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

______________________________________________________
ADDENDUM: PLEASE READ!!
INTRODUCING SHER FERTILITY SOLUTIONS (SFS)
Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

PLEASE SPREAD THE WORD ABOUT SFS!

Geoff Sher

reply
Lisa

Thank you so much Dr Sher for your detail message, I will coordinate with my fertility doctor and try to see if she can incorporate this in my treatment plan. Thank you so much, I really appreciate you.

Dr. Geoffrey Sher

You are very welcome, Lisa!

Good luck!

Geoff Sher

Brianna Kenney

Hello,

I am about 4 weeks pregnant today and had my first HCG blood draw at 3 weeks 5 days and it was 48. Today I got it back and it was 45. Does this sound like a chemical pregnancy to you? They told me to go back in 3 days to get one more blood draw

reply
Dr. Geoffrey Sher

Sadly, this does not look promising!

Sorry!

Geoff Sher

Wendy

Hi Dr Sher.
I had a 5 day blastocyst transfer on 18th August. I then had a blood test on 31st August and they said I had a low positive result of 65. They said it should be around 90-100. I am having another blood test on 7th September but the wait is killing me. I’m using home urine test and the positive line has faded since I first tested 5 days ago. Is this a bad sign? What is the cause of a low positive? I have no cramping or bleeding but I don’t know if it’s too soon to feel the side effects of ectopic pregnancy or miscarriage or blighted ovum.
Can you please advise what I can expect to happen?
Thank you ever so much.

Dr. Geoffrey Sher

Unfortunately, there is no other choice than to await an ultrasound at around 6-7 weeks!

Sorry!

Geoff Sher

Dana

First, thank you for your site. What a wonderful place to visit when you are anxious. I just turned 38 we have a 2 year old from a natural conception.

We started IVF this year. We had 2 prior failed cycles (1 retrieval with no eggs found). Extremely low AMH and FSH was 18 this current cycle. Also had 2 prior miscarriages before IVF (one of unknown origin/possible ectopic).

Current cycle, I didn’t realize I was supposed to start ganerelix and Dr. thought I was ovulating. He told us to have relations and it looked like 2 follicles may have released eggs.

14dpo – 198 hcg
17dpo – 662hcg
24dpo- 13,000hcg
I have a scan scheduled next week. Is this likely a molar pregnancy or some chromosomal issue? Or are we really this lucky to have a strong healthy pregnancy or twins?

reply
Dr. Geoffrey Sher

In my opinion these hCG levels look promising for a potentially viable pregnancy.

Good luck and G-d bless!

Geoff Sher

reply
Dana Gabriel

Thank you again for your time and support- US showed one baby measuring 6 weeks 4 days! So blessed.

reply
Rachel

I’m worried that my beta doubling time is slowing down 🙁

13 DPO – 103 HCG
15 DPO – 278 HCG
17 DPO – 500 HCG
19 DPO – 895 HCG

Doubling times started off at 32 hours, but is now at 57 hours. What do you think?

reply
Dr. Geoffrey Sher

I am still guardedly optimistic. Do an US in 10-14 days. That should be definitive.

Good luck and G-d bless!

Geoff Sher

reply
Alterego

Hi,

I had a single frozen embryo transfer on July 15th and did my first beta hcg test on July 27(12th day after transfer) .

The hcg level is 1924.

Does this looks normal for a single embryo transfer.Is there any chances of multiple pregnancy?

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Hope

Hello,
I had some dark red/brown blood when I wiped twice, both wipes were minimal, maybe the size of a quarter with no clots on 7/24. The bleeding never returned after wiping. Because of this I was sent to get my HCG levels checked. The first level was 12,526, 48 hours later the HCG level was at 13,362. Because they weren’t doubling, I was sent in for an ultrasound. I found out I had a retroverted uterus, so it was extremely hard to see the baby or detect a heartbeat. We were able to see it and it’s measuring at 6 weeks 4 days. I’m being sent back in 8 days for another ultrasound so we can get a better visual and hopefully hear the heartbeat. I know all I can do is wait right now, but the HCG numbers are making me a bit nervous. I was wondering what your thoughts would be on this. Thank you so much!

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Dr. Geoffrey Sher

Vaginal bleeding occurs in about 25% of all pregnancies. When it happens, it almost invariably raises the concern of pregnancy loss (miscarriage). Bleeding can also be a sign of a tubal (ectopic) pregnancy, and in cases where the distended Fallopian tube ruptures it can precipitate a life-threatening crises. However, a small amount of painless vaginal bleeding can also be the result of normal embryo implantation (i.e. implantation bleeding) or it can result a local erosion of the vagina or cervix and/or trauma during intercourse.

Geoff Sher

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Lindsay

Hello,

I had a miscarriage about 4 months ago at 5 weeks 3 days. My last period was on June 14th, and I tested positive on July 18th.

I had my first HCG drawn on 7/22 – 3881
My second HCG draw was on 7/24 – 5726

The values not doubling are concerning to me given my previous miscarriage. Should I be worried?

Thank you

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Dr. Geoffrey Sher

I would not be overly concerned. Once the level teaches 5000-6000 it no longer doubles every 2 days!

Geoff Sher

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Michelle Zammit

Thank you for that information! I am 10dp5dt and my beta today was 106. I’m going back in two days, but I’ve been told that I can be ‘cautiously optimistic.’ I’m 41 – does age affect the hcg level and is it that low? Thanks

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Dr. Geoffrey Sher

As log as it doubles in 2 days you should likely be fine.

Geoff Sher

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Erica Jehn

Hi my hcg says I’m measuring at 7 and a half weeks but my ultrasound said I was only 4 or 5 weeks. Twins run in my family why is the blood test higher than the scan?

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Dr. Geoffrey Sher

The hCG level is not an accurate reflection of gestational age. The US is far more reliable.I suggest you repeat the US in 10-14 days.

Good luck!

Geoff Sher

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oonagh

Hi , I am 37 and had my first embryo transfer on 21/07/20. I didn’t get a positive line until 12dp5dt.

My first beta was 80 , I tested 2 days later and it was 146. I did another blood test 4 days later and it is only at 266.

Am I heading for a miscarriage?

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Dr. Geoffrey Sher

This could be a failing implantation! I hope I am wrong!

Sorry!

Geoff Sher

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Candice

I went to the ER on 7/23/20 due to sickness. I am about 6w6d pregnant and my levels were at 3,306. Is this considered normal for this gestational age?

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