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Ectopic (Tubal) Pregnancy and IVF

by Dr. Geoffrey Sher on April 25, 2016

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. 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

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.

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  • Mum100 - November 17, 2016 reply

    Hi Dr Sher, thanks for this helpful article. My first IVF in May 2016 resulted in an ectopic pregnancy and left salpingectomy. I’m currently 7 weeks and 5 days pregnant after my second FET (unmedicated cycle). They transferred two blastocysts. The 7 week scan confirmed 1 viable uterine pregnancy with a heartbeat. When the nurse scanned, she saw the corpus luteum on left hand side and my left ovary. However, she could not find my right ovary – she said it might have “gone to sleep”. I did have momentary soreness when she was looking for my right ovary with the transvaginal scanner. I have had no bleeding at all during this pregnancy, however. I guess I’m asking whether I should request another scan before 12 weeks, given my history of ectopic and the current situation – to be sure that this pregnancy isn’t heterotopic? Thanks in advance for your advice. Charlotte (London, England)

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 17, 2016 reply

    Heterotopic pregnancies are very rare (<1:1000) so in all likelihood everything will be OK. However, it is wise to have a second U}S at around 10 weeks, anyway.

    Geoff Sher

    Charlotte - November 17, 2016 reply

    That’s really helpful, Doctor Sher. Thank you. PS I really enjoy your blogs.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - November 17, 2016 reply

    Thank you Charlotte!

    Geoff Sher

  • Kelly - October 17, 2016 reply

    Hi Dr. Sher,
    I had a question about your protocol for IVF prep post ectopic pregnancies…..
    I have a son (naturally concieved at age 33, no issues). I am now 37 and xince trying for a second, I have had 2 ectopic pregnancies both on the left side. HSG came back clear on both sides. My OB suspects endometriosis as well, I have a history of symptoms but no test confirmation. My RE is recommending removing the left tube and possible right tube prior to IVF. I am on board with removing left tube but it seems extreme to remove right tube, although I understand why it is a consideration. I don’t want to give up all chances of concieving naturally should IVF fail. Would love to know what you would do.
    Thank you

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - October 17, 2016 reply

    That is a personal decision. However in deciding whether to remove one or both tubes, bear in mind the the commondest cause of ectopic pregnancy is previous tubal damage due to inflammation and that when tubal inflammation occurs, it almost always affects both tubes. So removing 1 tube does not rule out a subsequent ectopic in the other.

    By the way, respectfully, I do not believe endometriosis is responsible here. It rarely affects the tube wall or the innerf lining.

    Good luck!

    Geoff Sher

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