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

by Dr. Geoffrey Sher on December 23, 2015

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.
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  • Laura - February 17, 2018 reply

    Hi I had a blood hcg level drawn at 4 weeks 4 days and level was 147 and progesterone 14. They had me do a repeat beta hcg test a little less than 72 hours. Is this concerning?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 17, 2018 reply

    It all depends on what the repeat beta hCG is. It should be around 450 or better.

    Geoff Sher

  • Tara E - February 13, 2018 reply

    Hi Dr. Sher!
    Thank you for this wonderful website and for all the time that you take to insightfully answer these questions.

    I had a naturally occurring pregnancy that ended in a natural miscarriage around 8-9 weeks in 2013 and then went on to conceive via IUI with injectable meds in 2014. That pregnancy resulted in 1 healthy, full term baby and also had an empty gestational sac that was resorbed. I then conceived with Clomid in 2016, which resulted in another healthy, full term baby. Most recently, I conceived naturally late in 2017, which ended in a blighted ovum at 7 weeks (D and C was performed). I am now pregnant again (unexpectedly) immediately after the D and C procedure in January and awaiting HCG and progesterone results. Is this pregnancy likely to result in another miscarriage since it was so close to my D and C, given my history? It should be noted that I am also still nursing my youngest baby, however, in the process of weaning.

    Should I revisit my RE to look into the cause of my RPL?

    Thank you so much for your time and expertise.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 13, 2018 reply

    I think it is too late now. So give this pregnancy a chance and if you lose it…then see your RE regarding RPL.

    Geoff Sher

  • Renee - February 8, 2018 reply

    Hi Dr. Sher
    I came across your article and was curious on your thoughts about my Beta numbers so far. I transferred 2 fresh 5 day blasts (4AA and 4BB). My first beta was 10dp5dt 191.7 and then my second beta was 13dp5dt 807.1. With my numbers more than doubling could that indicate both implanted?

    Thank you!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 8, 2018 reply

    Looks promising!

    Good luck!

    Geoff Sher

  • Juliet - February 3, 2018 reply

    Dear Dr Sher,
    First, thank you for your informative site and your q/a support.
    I have had a 5 day transfer of 1 grade A blastocyst with PGD on Jan 12
    I am very nervous because my HCG is not rising properly.

    10dp5dt 81
    12dp5dt. 200
    14dp5dt. 400
    18dp5dt. 929 = 23 dpo

    So the numbers started fine, but over the last 4 days the rise has been very slow, below 2 times in 3 days, the last level is below the lowest bound of the norm for 23dpo, and the 1 week rise is well below the recommended 15 times as well.

    I am very scared… Do you think there is a chance for this pregnancy to have a positive outcome ?

    Thank your ofr your time and support.

    Juliet

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - February 4, 2018 reply

    Yes Juliet , I am optimistic that all will be OK. Please keep me in the loop!

    Good luck and G-d bless!

    Geoff Sher

  • mary - January 26, 2018 reply

    Hi Doctor. At 4 weeks 4 days, my hcg was 863,9. i did not take second test hcg. is it a good sign of pregnancy? thanks a lot Doctor.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 26, 2018 reply

    Yes it is …but you should measure the hCG again in 2 days to see if it at least doubles.

    Geoff Sher

  • Kelly - January 1, 2018 reply

    Hello. I had my first beta yesterday, Sunday, at 9dp5dt and my level was at 15. I go back tomorrow, Tuesday. What number should I hope to see the hcg increase to? I’m so nervous.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 1, 2018 reply

    Above 30!

    Happy New Year!

    Geoff Sher

    Jane Smith - January 11, 2018 reply

    13dpo (1 day before period was due) hcg was only 6; 16dpo hcg was 16 (so doubling between 48-72 hours; 18dpo hcg is 42…more than doubled. From 16dpo to 18dpo progesterone increases frim 7-10 and estrogen went from 456-558. Doctor is acting like it’s already over. Not viable she says because numbers are so low. But what if I implanted late? What do u think?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 11, 2018 reply

    Only time will tell but there is hope!

    Good luck!

    Geoff Sher

    Jane Smith - January 11, 2018 reply

    So you think there is actually a chance it’s viable?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 11, 2018

    Modest…but yes!

    Geoff Sher

    Jane Smith - January 11, 2018

    Ok thank you. I have had two early miscarriages already this year so perhaps that’s why my doctor is already calling this inevitable miscarriage.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - January 11, 2018

    Copy!

    Geoff Sher

  • Aggy - December 24, 2017 reply

    Hi Dr ,I had 3dFET on 13 dec2017 then went for beta hcg on 22 DEC which was 9dpt and my hcg was 4.85 my Dr advice me to recheck 4 days later is it possible for this no.to increase

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 24, 2017 reply

    Hi Aggy,

    Sadly this does not look promising!

    G-d bless!

    Geoff Sher

  • Karen - December 22, 2017 reply

    I had 2 fresh embryos transferred. And my HCG results are …. 14 DPO/11 dp3DT = 64, 17 DPO/ 14 dp3dt = 160, 20 DPO/ 17 dp3dt = 240, 21 DPO/ 18 dp3dt = 279. I am worried that my results were more than doubling and have now slowed down. Is this possibly due one of the embryos not taking?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 23, 2017 reply

    Hi karen,

    This does not look very promising to me. I am afraid that implantation could be failing here, unless you started with 2 and are in the process of reducing down to one implantation now. I hope I am wrong!

    G-d bless and good luck!

    Geoff Sher

    Karen - December 23, 2017 reply

    Thank you. I will stay hopeful over the Christmas period. My scan isn’t until 8th Jan. So far there’s no pain and no spotting. Although, I am on 400mg progesterone twice a day, which could be keeping anything sinister at bay.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 23, 2017 reply

    Copy and G-d bless!

    Geoff Sher

  • Tina - December 22, 2017 reply

    Hi. I took a test on the day before my period was due and had an HCG drawn the following day (period due date) that was 485. What range does that put me in? 4 or 5 weeks?

    Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 23, 2017 reply

    Hard to say, but an US done 7-10 days drom now should provide an answer.

    Good luck and G-d bless!

    Geoff Sher

  • Kaye - December 21, 2017 reply

    Hi Dr. Sher,
    Do you believe that the HCG level can indicate multiples? I had a 5-day fresh transfer on 12/11 (two embryos transferred – 4BB and 2BB). I started seeing positive home pregnancy tests Saturday, and my first beta today was at 658. This is almost triple the HCG level I had with my daughter after my first IVF cycle a few years ago (it was 213). Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 21, 2017 reply

    More important is how the level up in 2 days time. If it triples or greater, it could be a multiple.

    Good luck!

    Geoff Sher

    Kaye - December 28, 2017 reply

    Hi Dr.Sher – we had the second test today (exactly one week later) and the HcG level is now 12,965. Is that normal or could it be multiples (it was 658 last Thursday- 10dp5dt). Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 28, 2017 reply

    Could be multiples!

    Good luck kaye!

    Geoff Sher

  • Jennifer - December 21, 2017 reply

    Hi Dr.

    I had an IUI on 12/1 and got a BFP. I went in for my HCG test on 12/18 and it was at 350 and then went back 12/20 and it was only 489. They told me its concerning but doesn’t mean its necessarily a loss. I had read that for IUI a 35% increase is needed, but then other things say it needs to double. What would be your perspective on this? I’m worried I went through all of this for nothing..

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 21, 2017 reply

    There needed to ideally be a doubling in 48h. this is of concern but it could be that you started with >1 pregnancy and one is absorbing. Unfortunately only time will tell!

    Geoff Sher

  • Siu - December 15, 2017 reply

    Hello! I had a fresh transfer and yesterday 10dp5dt had my first beta which was 16. It seems really low and I am worried about it. Also, we planned a trip this upcoming weekend. Is it recommended to flight? What do you think about that low result? Thank you so much for all the info you provide!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 15, 2017 reply

    I personally would recommend that you stay put until you know which way the “pregnancy” is headed.

    Good luck!

    Geoff sher

    Siu - December 16, 2017 reply

    Thank you so much for getting back! Do you think is too low the hcg level?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 16, 2017 reply

    What is really relevant is whether it doubles every 2 days.

    Good luck!

    Geoff Sher

    Haylee Szumlinski - December 16, 2017 reply

    Hello doctor I’m wondering what your opinion would be. I had a TV ultrasound at 5 weeks 6 days that showed a gestational sac and a yolk sac. No fetal pole was seen. A SCH was also detected. Hcg was checked that same day with a level of 2717. Progesterone came back that day very low so I was started on Crinone. Two days later at 6 weeks 1 days hcg was at 3732. No bleeding or spotting but non stop cramping. Doctor was worried with the rise and said it didn’t double how they wanted it to. I go in twice next week for more blood draws. I wish they would do an Us to determine viability. Would you say that my chance of miscarrying or that I already have is high at this point? Thank you so much I just want to prepare myself.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 17, 2017 reply

    It is difficult to say with an US done so early. You need to repeat it in 1 week.

    Good luck!

    Geoff Sher

    Geoff Sher

  • Sarah Nolan - December 14, 2017 reply

    Dr Sher,

    Just got my beta back – my HCG is 7.99, (9dp5dt, FET). My nurse said to be “cautiously optimistic” but this seems way too low to be viable. Any thoughts? Thanks!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 14, 2017 reply

    The level is low…so please hope for the best and prepare for the worst!

    G-d bless!

    Geoff Sher

  • Carrie Garner - December 13, 2017 reply

    Hello Dr. I am on my 4th round of off. Resulting in a bfn, mc at 4 weeks, bfn, and lastly BPD. I had an fet Nov 30 2017. I chose to have 2 embryos transfered. My first beta was on Dec. 11, 2017 reading 1444. Second beta Dec. 13, 2017 reading 4063.2
    I won’t be back to Dr. Visit until Dec. 21, 2017 for an ultrasound. How would you view my experience. Or do you have any advice Thank you Dr.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    Sounds very promising…possibly even twins!

    Good luck!

    Geoff Sher

  • Tammy - December 13, 2017 reply

    Hello Doctor. Found out today that I am 5 weeks 6 days pregnant. I am very excited that this round of IVF worked. The did an ultrasound and said everything looks good. I returned home and now I am bleeding red blood, not brown, quite a lot and I have just passed a large clot (larger than a quarter) I am very scared that I am now miscarrying.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    My thoughts are with you Tammy! Unfortunately, aside from trying to avoid any over-activity until hopefully the bleeding stops , there is nothing you can do except wait it out.

    I wish you well!

    Please keep me updated.

    Geoff Sher

    Tammy - December 13, 2017 reply

    Update: It was a subchorionic hematoma! Phew! The ultrasound and bloodworm this morning look good to the doctor. The bleeding stopped overnight, and I am still feeling no discomfort. I have been instructed to rest for a few days and return next week for a check up. Thank you for your encouraging words.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    I am so happy for you!

    G-d bless and good luck!

    Geoff Sher

  • TMR - December 12, 2017 reply

    Me again. Just went for an ultrasound today to check on everything. Doctor said they saw the yolk sac and fetal pole, but still too early to see the heartbeat. Been having very scant brown discharge, but since I got home from the ultrasound, discharge has become more watery and lighter in colour. Could the ultrasound have caused this? Office is closed, so I can’t call to ask.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    I would not be concerned about a non-bloody discharge!

    Good luck!

    Geoff Sher

  • TMR - December 11, 2017 reply

    Hello,
    20dp5dt transferred 1 4BB hatching blastocyst as of today. Started beta tests on 14dp. Started with 576 then 1303, 2679, today 4288. Doctor wants an ultrasound tomorrow since I didn’t double in 48hrs. Do I have reason to be concerned?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 12, 2017 reply

    My bet is that all will be well!

    Good luck!

    Geoff Sher

  • Heather - December 6, 2017 reply

    Hi Dr. Sher,
    How many embryos (percentage wise) typically make it from day 3 to day 5-6 (Blast stage)?
    I had 11 embryos at day 3 and only 4 made it to day 5. What factors play into a poor outcome like this? If we need to do another cycle- is there anything I could do to help increase the amount of day 5 blasts?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    Age and the cause of the infertility both impact blastocyst conversion rates. For younger women (<35y) who have normal ovarian reserve, the conversion rate of cleaved embryos to blastocysts is about 40% and the percentage of these blastocysts that are chromosomally normal = about 50%. The older the women the lower these statistics become so that bu the mid-40's the rates would be about 15% and 10% respectively.

    The only way to optimize this conversion is to implement an optimal protocol for ovarian stimulation.

    Here is the protocol I advise for women, <40Y who have adequate ovarian reserve.
    My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur---no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
    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.
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • 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
    • “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Hanah - December 6, 2017 reply

    Hi thank you Doctor for your reply. Would you concur with my doctor also to be optimistic with my numbers? They seem to be thinking my numbers were good but to me they seem low.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    Guardedly optimistic!

    Geoff Sher

    Hannah - December 13, 2017 reply

    Thank you doctor. I’m currently 6 weeks 4 days and go in for ultra sound tomorrow. I’m pretty nervous but still no signs of miscarriage this far in. I wish my numbers were better or I had them rechecked again. The not knowing is so tough. Are things pointing more positively being 6 weeks 4 days and no signs of miscarriage?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 13, 2017 reply

    Good luck and G-d bless!

    Geoff Sher

    Hannah - December 14, 2017

    Hi Doctor. Good news. They found the baby measuring at 6 weeks 4 days which is one day behind with a heartbeat of 123. they said that was a good heartbeat. Thank you.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 14, 2017

    So happy for you!

    Geoff Sher

  • Hanah - December 6, 2017 reply

    Hi Doctor. I had two 3 day frozen embryos transferred and my HCG levels have been concerning.

    13 days after transfer 143
    15 days after transfer 210
    17 days after transfer 387
    20 days after transfer 1026

    The first to second tests only went up 48 percent but then the doubling rate got on track after that. Also the 1026 level seems low for 20 days after transfer. My doctor stopped ordering HCG testing and I’m going in for US in 9 days.

    Should I be worried with my HCG level?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    I concur with your RE’s decision. It will take an US to tell at this stage.

    Geoff Sher

  • Marissa - December 6, 2017 reply

    Hi Dr. Sher! I have had 2 previous ectopic Pregnancies. 1 treated with a salpingectomy and the 2nd with methotrexate. Hsg after treatment showed an open tube. I just got a positive pregnancy test and hcg is 27, progesterone 11. I am anywhere from 3 weeks 6 days to 4 weeks 1 day. Do you think this could be indicative of another ectopic?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    It is impossible to say with any confidence at this stage. You need to repeat the test in 2 days to see how the level is changing and if it doubles. Thereafter, an ultrasound in about 2-3 weeks time will confirm one way or the other.

    Good luck!

    Geoff Sher

  • Megan Joyner - December 5, 2017 reply

    Hi Dr. Sher – I’ll try to make this brief. My husband and I are both 36. We have a healthy 8 year old son, no problems conceiving or with the pregnancy and delivery. We have now been trying for 4 years for # 2 and we’ve had a chemical, a 15 weeks loss, another chemical, another 16 week loss, an 8 week loss, and a blighted ovum, in that order. 6 consecutive losses. The second tri losses and 8 week loss were tested and had normal chromosomes. I have beea on a combination of plaquenil, prednisone, lovenox, asa, estrogen, progesterone, and neupogen for several of these pregnancies. I have Sjogren’s, mildly elevated anticardiolipin IgM antibodies, positive ANA, mildly elevated NK cell activity, low uterine NK activity, and am hypothyroid. How I had a healthy child with no complications is a sheer miracle in itself, apparently.

    I recently found out I was pregnant on an immune protocol after doing a TI cycle with femara days 3-7, second month trying. I had 4 large follies ready to rupture. I did not do a trigger. I got a very faint positive at 9dpo. Here is a summary of my betas so far. They are rising erratically and have sort of slowed down. Just curious if you have seen any similar betas that ended with a take home baby. I am currently on prednisone, plaquenil, lovenox, asa, neupogen, metanx, synthroid, estradiol, and oral and vag and PIO progesterone, all before conception. I know it is up to God at this point, truly. Any feedback is appreciated.

    11/14 9dpo 7
    11/16 11dpo 29 (314% rise) DT 23 hrs
    11/18 13dpo 58 (100% rise)) DT 48 hrs
    11/20 15dpo 102 (76% rise) DT 59 hrs
    11/22 17dpo 146 (43% rise) different lab, DT 92 hrs
    11/24 19dpo 312 (113% rise) DT 44 hrs
    11/27 22dpo 698 (71% rise over 2 days) DT 62 hrs
    11/28 Gestational sac seen on US 5w0d
    11/29 24 dpo 988 (41% rise) Out of state lab DT 95 hrs
    12/1 26dpo 1540 (55.9% rise) DT 75 hrs
    12/4 29dpo 2063 (21% rise) DT 170 hrs – also had a repeat scan today and a yolk was seen in addition to the gestational sac. Measuring 5w5d and I am 5w6d.

    Thank you in advance for you time and feedback.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 6, 2017 reply

    I am afraid…this does not look very encouraging. You could be on yourv way to another loss…I hope I am wrong but only time will tell for certain.

    What stands out to me is that you could have an implantation issue. I am concerned about an immunologic cause, given your history of recurrent loss with chromosomally intact embryos. Also, hypothyroidism is usually autoimmune in women and if so, there is a 50:50 chance of natural killer cell activation which if present has not been fully addressed , in my opinion.

    When it comes to reproduction, humans are the poorest performers of all mammals. In fact we are so inefficient that up to 75% of fertilized eggs do not produce live births, and up to 30% of pregnancies end up being lost within 10 weeks of conception (in the first trimester). RPL is defined as two (2) or more failed pregnancies. Less than 5% of women will experience two (2) consecutive miscarriages, and only 1% experience three or more.
    Pregnancy loss can be classified by the stage of pregnancy when the loss occurs:
    • Early pregnancy loss (first trimester)
    • Late pregnancy loss (after the first trimester)
    • Occult “hidden” and not clinically recognized, (chemical) pregnancy loss (occurs prior to ultrasound confirmation of pregnancy)
    • Early pregnancy losses usually occur sporadically (are not repetitive).
    In more than 70% of cases the loss is due to embryo aneuploidy (where there are more or less than the normal quota of 46 chromosomes). Conversely, repeated losses (RPL), with isolated exceptions where the cause is structural (e.g., unbalanced translocations), are seldom attributable to numerical chromosomal abnormalities (aneuploidy). In fact, the vast majority of cases of RPL are attributable to non-chromosomal causes such as anatomical uterine abnormalities or Immunologic Implantation Dysfunction (IID).
    Since most sporadic early pregnancy losses are induced by chromosomal factors and thus are non-repetitive, having had a single miscarriage the likelihood of a second one occurring is no greater than average. However, once having had two losses the chance of a third one occurring is double (35-40%) and after having had three losses the chance of a fourth miscarriage increases to about 60%. The reason for this is that the more miscarriages a woman has, the greater is the likelihood of this being due to a non-chromosomal (repetitive) cause such as IID. It follows that if numerical chromosomal analysis (karyotyping) of embryonic/fetal products derived from a miscarriage tests karyotypically normal, then by a process of elimination, there would be a strong likelihood of a miscarriage repeating in subsequent pregnancies and one would not have to wait for the disaster to recur before taking action. This is precisely why we strongly advocate that all miscarriage specimens be karyotyped.
    There is however one caveat to be taken into consideration. That is that the laboratory performing the karyotyping might unwittingly be testing the mother’s cells rather than that of the conceptus. That is why it is not possible to confidently exclude aneuploidy in cases where karyotyping of products suggests a “chromosomally normal” (euploid) female.
    Late pregnancy losses (occurring after completion of the 1st trimester/12th week) occur far less frequently (1%) than early pregnancy losses. They are most commonly due to anatomical abnormalities of the uterus and/or cervix. Weakness of the neck of the cervix rendering it able to act as an effective valve that retains the pregnancy (i.e., cervical incompetence) is in fact one of the commonest causes of late pregnancy loss. So also are developmental (congenital) abnormalities of the uterus (e.g., a uterine septum) and uterine fibroid tumors. In some cases intrauterine growth retardation, premature separation of the placenta (placental abruption), premature rupture of the membranes and premature labor can also causes of late pregnancy loss.
    Much progress has been made in understanding the mechanisms involved in RPL. There are two broad categories:
    1. Problems involving the uterine environment in which a normal embryo is prohibited from properly implanting and developing. Possible causes include:
    • Inadequate thickening of the uterine lining
    • Irregularity in the contour of the uterine cavity (polyps, fibroid tumors in the uterine wall, intra-uterine scarring and adenomyosis)
    • Hormonal imbalances (progesterone deficiency or luteal phase defects). This most commonly results in occult RPL.
    • Deficient blood flow to the uterine lining (thin uterine lining).
    • Immunologic implantation dysfunction (IID). A major cause of RPL. Plays a role in 75% of cases where chromosomally normal preimplantation embryos fail to implant.
    • Interference of blood supply to the developing conceptus can occur due to a hereditary clotting disorder known as Thrombophilia.
    2. Genetic and/or structural chromosomal abnormality of the embryo.Genetic abnormalities are rare causes of RPL. Structural chromosomal abnormalities are slightly more common but are also occur infrequently (1%). These are referred to as unbalanced translocation and they result from part of one chromosome detaching and then fusing with another chromosome. Additionally, a number of studies suggest the existence of paternal (sperm derived) effect on human embryo quality and pregnancy outcome that are not reflected as a chromosomal abnormality. Damaged sperm DNA can have a negative impact on fetal development and present clinically as occult or early clinical miscarriage. The Sperm Chromatin Structure Assay (SCSA) which measures the same endpoints are newer and possibly improved methods for evaluating.

    IMMUNOLOGIC IMPLANTATION DYSFUNCTION
    Autoimmune IID: Here an immunologic reaction is produced by the individual to his/her body’s own cellular components. The most common antibodies that form in such situations are APA and antithyroid antibodies (ATA).
    But it is only when specialized immune cells in the uterine lining, known as cytotoxic lymphocytes (CTL) and natural killer (NK) cells, become activated and start to release an excessive/disproportionate amount of TH-1 cytokines that attack the root system of the embryo, that implantation potential is jeopardized. Diagnosis of such activation requires highly specialized blood test for cytokine activity that can only be performed by a handful of reproductive immunology reference laboratories in the United States.
    Alloimmune IID, i.e., where antibodies are formed against antigens derived from another member of the same species, is believed to be a relatively common immunologic cause of recurrent pregnancy loss.
    Autoimmune IID is often genetically transmitted. Thus it should not be surprising to learn that it is more likely to exist in women who have a family (or personal) history of primary autoimmune diseases such as lupus erythematosus (LE), scleroderma or autoimmune hypothyroidism (Hashimoto’s disease), autoimmune hyperthyroidism (Grave’s disease), rheumatoid arthritis, etc. Reactionary (secondary) autoimmunity can occur in conjunction with any medical condition associated with widespread tissue damage. One such gynecologic condition is endometriosis. Since autoimmune IID is usually associated with activated NK and T-cells from the outset, it usually results in such very early destruction of the embryo’s root system that the patient does not even recognize that she is pregnant. Accordingly the condition usually presents as “unexplained infertility” or “unexplained IVF failure” rather than as a miscarriage.

    Alloimmune IID, on the other hand, usually starts off presenting as unexplained miscarriages (often manifesting as RPL). Over time as NK/T cell activation builds and eventually becomes permanently established the patient often goes from RPL to “infertility” due to failed implantation. RPL is more commonly the consequence of alloimmune rather than autoimmune implantation dysfunction.
    However, regardless, of whether miscarriage is due to autoimmune or alloimmune implantation dysfunction the final blow to the pregnancy is the result of activated NK cells and CTL in the uterine lining that damage the developing embryo’s “root system” (trophoblast) so that it can no longer sustain the growing conceptus. This having been said, it is important to note that autoimmune IID is readily amenable to reversal through timely, appropriately administered, selective immunotherapy, and alloimmune IID is not. It is much more difficult to treat successfully, even with the use of immunotherapy. In fact, in some cases the only solution will be to revert to selective immunotherapy plus using donor sperm (provided there is no “match” between the donor’s DQa profile and that of the female recipient) or alternatively to resort to gestational surrogacy.
    DIAGNOSING THE CAUSE OF RPL
    In the past, women who miscarried were not evaluated thoroughly until they had lost several pregnancies in a row. This was because sporadic miscarriages are most commonly the result of embryo numerical chromosomal irregularities (aneuploidy) and thus not treatable. However, a consecutive series of miscarriages points to a repetitive cause that is non-chromosomal and is potentially remediable. Since RPL is most commonly due to a uterine pathology or immunologic causes that are potentially treatable, it follows that early chromosomal evaluation of products of conception could point to a potentially treatable situation. Thus I strongly recommend that such testing be done in most cases of miscarriage. Doing so will avoid a great deal of unnecessary heartache for many patients.
    Establishing the correct diagnosis is the first step toward determining effective treatment for couples with RPL. It results from a problem within the pregnancy itself or within the uterine environment where the pregnancy implants and grows. Diagnostic tests useful in identifying individuals at greater risk for a problem within the pregnancy itself include:

    • Karyotyping (chromosome analysis) both prospective parents
    • Assessment of the karyotype of products of conception derived from previous miscarriage specimens
    • Ultrasound examination of the uterine cavity after sterile water is injected or sonohysterogram, fluid ultrasound, etc.)
    • Hysterosalpingogram (dye X-ray test)
    • Hysteroscopic evaluation of the uterine cavity
    • Full hormonal evaluation (estrogen, progesterone, adrenal steroid hormones, thyroid hormones, FSH/LH, etc.)
    • Immunologic testing to include:
    a) Antiphospholipid antibody (APA) panel
    b) Antinuclear antibody (ANA) panel
    c) Antithyroid antibody panel (i.e., antithyroglobulin and antimicrosomal antibodies)
    d) Reproductive immunophenotype
    e) Natural killer cell activity (NKa) assay (i.e., K562 target cell test)
    f) Alloimmune testing of both the male and female partners
    TREATMENT OF RPL
    Treatment for Anatomic Abnormalities of the Uterus: This involves restoration through removal of local lesions such as fibroids, scar tissue, and endometrial polyps or timely insertion of a cervical cerclage (a stitch placed around the neck of the weakened cervix) or the excision of a uterine septum when indicated.
    Treatment of Thin Uterine Lining: A thin uterine lining has been shown to correlate with compromised pregnancy outcome. Often this will be associated with reduced blood flow to the endometrium. Such decreased blood flow to the uterus can be improved through treatment with sildenafil and possibly aspirin.
    Sildenafil (Viagra) Therapy. Viagra has been used successfully to increase uterine blood flow. However, to be effective it must be administered starting as soon as the period stops up until the day of ovulation and it must be administered vaginally (not orally). Viagra in the form of vaginal suppositories given in the dosage of 25 mg four times a day has been shown to increase uterine blood flow as well as thickness of the uterine lining. To date, we have seen significant improvement of the thickness of the uterine lining in about 70% of women treated. Successful pregnancy resulted in 42% of women who responded to the Viagra. It should be remembered that most of these women had previously experienced repeated IVF failures.

    Use of Aspirin: This is an anti-prostaglandin that improves blood flow to the endometrium. It is administered at a dosage of 81 mg orally, daily from the beginning of the cycle until ovulation.
    Treating Immunologic Implantation Dysfunction with Selective Immunotherapy: Modalities such as IL/IVIg, heparinoids (Lovenox/Clexane), and corticosteroids (dexamethasone, prednisone, prednisolone) can be used in select cases depending on autoimmune or alloimmune dysfunction.
    The Use of IVF in the Treatment of RPL
    In the following circumstances, IVF is the preferred option:
    1. When in addition to a history of RPL, another standard indication for IVF (e.g., tubal factor, endometriosis, and male factor infertility) is superimposed.
    2. In cases where selective immunotherapy is needed to treat an immunologic implantation dysfunction.
    The reason for IVF being a preferred approach in such cases is that in order to be effective, the immunotherapy needs to be initiated well before spontaneous or induced ovulation. Given the fact that the anticipated birthrate per cycle of COS with or without IUI is at best about 15%, it follows that short of IVF, to have even a reasonable chance of a live birth, most women with immunologic causes of RPL would need to undergo immunotherapy repeatedly, over consecutive cycles. Conversely, with IVF, the chance of a successful outcome in a single cycle of treatment is several times greater and, because of the attenuated and concentrated time period required for treatment, IVF is far safer and thus represents a more practicable alternative
    Since embryo aneuploidy is a common cause of miscarriage, the use of preimplantation genetic diagnosis (PGD), with tests such as CGH, can provide a valuable diagnostic and therapeutic advantage in cases of RPL. PGD requires IVF to provide access to embryos for testing.
    There are a few cases of intractable alloimmune dysfunction due to absolute DQ alpha matching where Gestational Surrogacy or use of donor sperm could represent the only viable recourse, other than abandoning treatment altogether and/or resorting to adoption. Other non-immunologic factors such as an intractably thin uterine lining or severe uterine pathology might also warrant that last resort consideration be given to gestational surrogacy.
    The good news is that if a couple with RPL is open to all of the diagnostic and treatment options referred to above, a live birthrate of 70%–80% is ultimately achievable.

    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
    • Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the “Conventional” Antagonist Approach
    • 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.
    • The Role of Nutritional Supplements in Preparing for IVF

    If you are interested in seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *FYI
    The 4th edition of my newest book ,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

  • Dasha - December 2, 2017 reply

    Hi Dr. Sher, i’ve Had 5 pregnancies and on to the 6th right now. I’ve had 2 mc’s at 5 weeks, then a healthy baby girl 4 years ago, and 2 more mc’s at 5 weeks. Pregnant right now, conceived on Nov 6, had beta drawn on nov 29- 452, I’m very concerned that that’s a McDonald’s again:( What are your thoughts on this? Thank you so much

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 2, 2017 reply

    This probably is not a repetitive issue…based on the information you gave me.

    Good luck!

    Geoff Sher

  • Preeti - December 1, 2017 reply

    Hi Dr Sher, I went had a 3 day embryo transfer on Nov 6, 2017 and my first beta on Nov 17 was 36. Since then it has been rising oddly, went to 76, 83, 126, 356 and was 574 on Nov 30th. My Re said it isn’t normal and did an ultrasound and ordered a full pelvic sonogram too. They couldn’t find an ectopic and couldn’t find a viable sac. I have been asked to stop progesterone suppositories and am in holding pattern. Have to go back for more blood work. What do you think is going on? Regards, Preeti

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - December 2, 2017 reply

    This does not look promising Preeti. I think this is simply a chemical pregnancy but please make sure your RE continues to watch for an ectopic.

    Geoff Sher

  • MENNA - November 30, 2017 reply

    hi Dr. i had a blood test yesterday with a 0.25 result my last period was on the 7th of November and ovulation date according to my calendar was on the 22nd of November.

    does this mean that i am not pregnant for sure?do i need to re do the test after a while?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 30, 2017 reply

    I am afraid it does not look good Menna!

    Sorry!

    Geoff Sher

  • Hannah Medina - November 23, 2017 reply

    Hi dr! I had my beta drawn 11dp5dt it was only 11 48 hours later 18.. I did transfer 2 embies… I am concerned however with my son it started at 20 12dp5dt and doubled from there… could I just be someone who starts low? Or because it didn’t double does it sound like cp?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 24, 2017 reply

    Hopefully this is a false alarm. You need another beta hCG done 2 days after the last one. If that doubles you could be OK.

    Good luck!

    Geoff Sher

    Hannah Medina - November 24, 2017 reply

    I am waiting for results now.. if it doubles how many more blood draws do you think I should have.? I’m over betas already!!! I wish one part of this journey could be normal!!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 25, 2017 reply

    It depends on the level! BUT possibly one more!

    Geoff Sher

  • Julie A Steinhofer - November 22, 2017 reply

    Hi!!! I am 4 weeks 4 days today and my HCG was 55 and progesterone was 10.6. Is this concerning?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 22, 2017 reply

    It could be a little on the low side. Repeat in 2 days to see if it doubles.

    Good luck!

    Geoff Sher

  • Fouzia Khan - November 22, 2017 reply

    I am at 11dp5dt today on 22 Nov 2017. Yesterday at 10dp5dt my beta hcg level was 110. As we had only single grade 4AA embryo for FET. Is this levl okay at Day 10 of transfer. Tomorrow, second Beta is schedules.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 22, 2017 reply

    The level is fine but it needs to double every 2 days from here on out!

    Geoff Sher

    Fouzia Khan - November 24, 2017 reply

    Dear Dr.Geoffrey Sher
    Yesterday at day 12, we conducted 2nd beta that was 264 ( First bet two days ago was 110, it is more than doubbled with in two days. Is it Okay? Our RE is satisfied with this . As it is by Single 5Day Embryo. He asked me for U/S December 07/2017. He does not think to go for ny further beta level tests.
    Kindly give your expert opinion.
    Regards, Fouzia Khan Dubai UAE

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 24, 2017 reply

    That is good news!

    Good luck!

    Geoff Sher

    Fouzia Khan - November 25, 2017

    Thank You So much Dr.
    God bless you for guidence.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 25, 2017

    You are very welcome Fouzia!

    Geoff Sher

  • Becky - November 21, 2017 reply

    Hello, just came across your article. I believe I am approx 4/5 weeks pregnant. On Friday my HCG levels were 690 and on Sunday they had only risen to 900, the doctor performed an ultrasound yesterday and could see a gestational sac and yolk (The ultrasonographer performed one on Friday but couldn’t see anything) In your experience are there any happy outcomes from a hcg rising slowly? Thanks in advance, Becky

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 21, 2017 reply

    I would repeat the hCG in 2 days (from the last). If therfe is still a slow rise, it would, I am afraid be a poor prognostic sign. If it doubles or better, it could be that you started of with a single pregnancy and one was lost.

    Good luck!

    Geoff Sher

    Becky - November 21, 2017 reply

    Thank you, the hospital have told me they don’t want to repeat the blood test they just want to perform another scan in a weeks time. Fingers crossed!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 21, 2017 reply

    Good luck!

    Geoff Sher

  • Sandy - October 24, 2017 reply

    Hi Dr. Sher, At 4 weeks 2 days my HCG was 56. At 4 weeks 4 days, it was 58, and then 5 week 1 day it was 60. I’m assuming this isn’t going to be viable. But since the levels are rising (though VERY slowly), do you have any idea what else it could mean? Could this still potentially be a viable pregnancy? I’m also feeling symptoms of pregnancy (nauseous, headache, tired, sore breasts), so I’m confused! Any help would be appreciated!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 25, 2017 reply

    Hi Sandy!

    This sounds like a failing implantation…i.e. a chemical pregnancy!

    Sorry!

    Geoff Sher

    Sandy - October 25, 2017 reply

    Thanks for writing. Today – I ended up having a little bit of bleeding, nothing heavy like I’ve read online for a CP. It’s also brown. Is that normal? Will this become heavier? Once it’s done, does that mean my HCG levels will be back at 0 and we can start trying again? Thanks again for your help!

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 26, 2017 reply

    Unfortunately time is the only determinant.

    Geoff Sher

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