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Endometriosis: Its Everywhere, But in Small Amounts

No one really knows what causes endometriosis. The prevailing theory is that it is caused by menstrual blood that backs up through the tubes during one’s period. This blood also contains the shedding glands from the lining of the uterus (the endometrium). It’s these glands that start the problem. In some women, for unknown reasons, these glands stick and continue to grow in areas like the ovary (most common area), the tubes and other areas in the pelvis near the bladder and rectum. These growing glands, only in some cases, can cause scarring and inflammation that lead to tubal blockage and pain. Ten percent of women have endometriosis.
So when most people hear this for the first time they worry that they have it, and it’s their cause of infertility. Rest assured this is usually not the case. First, of the 10% of people who have it, the vast majority of them don’t have enough of it to cause any problem at all. They may have a spot the size of a dime in their ovary or in those other places, but its not enough to cause any of the problems listed above, including infertility. Second, there is a lot written about the ability of even a small amount of endometriosis to cause problems with ovulation, fertilization, embryo quality and implantation. There are not enough facts in the literature to support any of this, and most doctors today believe the only way endometriosis causes infertility is by causing scar tissue that interferes with tubal function. Some doctors like to perform a laparoscopy on every infertility patient, using the excuse that 10% of women have endometriosis, so we need find it and annihilate it. This is over operating, and fruitless. Other tests can be performed to look for endo, including an ultrasound and hysterogram. If these two tests are nomal, a laparoscopy may be indicated in only a small percentage of cases. A typical indication for laparoscopy will be discussed in the next entry.

References:

  • Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol. 1984 Aug;64(2):151-4.
  • Lebovic DI; Mueller MD; Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001; 75(1):1-10.
  • Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril .2002 77(6): 1148-1155.
  • Marcoux S, Maheux R, Berube S, et al. Canadian Collaboration Group on Endometriosis. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Eng J Med 1997; 377:212-22.
  • Berube S, Marcoux S, Langevin M, Maheux R, The Canadian Collaborative Group on Endometriosis. Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility. Fertil Steril 1998; 69:1034-1041.
  • Giudice LC, Kao LC. Endometriosis. Lancet. 2004 Nov 13-19;364(9447):1789-99.

 

But Doc, What went Wrong? Maybe Nothing.

Today’s story is of a women in her early 30’s who, as you might suppose, could not get pregnant. She tried for a while on her own, then moved on to insemination using fertility drugs, and then IVF. Her IVF cycle went very well. She responded very nicely to the drugs and had a more than adequate endometrium. She had a retrieval of plenty of eggs, and most of her embryos were of good quality. She did a day 5 transfer of 2 nice blastocysts. Everything looked good, but unfortunately, she did not get pregnant.
So want went wrong? Well sometimes the answer is nothing, it just didn’t work. The most plausible explanation is that despite her embryos looking normal, the embryos may have been genetically abnormal, and pregnancy did not occur. (this is not a push for PGD, the subject of another day).
To me this is not a story of despair, but a story of hope. Yes it’s sad, it didn’t work. However, everything in this woman’s cycle was pointed in the right direction. She is much better off that the person who has trouble stimulating or has a bad uterus or poor embryo quality. The odds of her becoming pregnant in her next cycle are still excellent. The problem becomes when we all try to micro analyze the cycle. Patients think, “Maybe it was my cold, or I picked up my daughter and got a cramp, or there was stress at work.” Doctors look at the medication protocols, day of hCG, ease of transfer and many other things. Every failure needs to be carefully reviewed, but in the end, sometimes it’s just a matter of trying again. The best thing a patient can do to help her odds is to get treatment at the best facility available to her.

FSH and Estradiol(Estrogen)

It is also important to measure the estradiol on day 3. Day 2 is fine. The reason its day 3 is 15-20 years ago, the IVF medications were always started on day 3. So everyone who started an IVF cycle had Estradiol and FSH measured on day 3. Pregnancy rates were checked against different levels of FSH and Estradiol, and that’s how the original work was done. I did research with the day 3 Estradiol level when I was a fellow.
If the estradiol level is high, the FSH level will be artificially lowered, and the FSH level will therefore not accurate. For example, I may have a patient with an FSH an 18 and an
estradiol level of 45. Next month the FSH is 8, but the Estradiol is 92. This is just as bad as her first test. Once the estradiol is over about 50, the FSH will be lowered. Just because the FSH becomes lower does not mean the patient is more fertile. If the estradiol is elevated month to month, this is as bad as the FSH being elevated month to month.
Why does the Estardiol level become elevated? For some women, the cycle gets shorter as their ovaries age. So that by day 3, when the follicle should not yet be growing, the follicle has already started to grow and produce estradiol, and for reasons we don’t yet understand, this is bad. Taking estrogen pills to lower the FSH level does not help. It’s like taking Tylenol to lower your temperature if you have appendicitis. Your temperature may come down, but there is still a problem. Some doctors say there is a benefit to lowering the FSH level with estrogen. They say that when the FSH is high, the ovary become resistant to FSH and can’t be stimulated by fertility drugs(which contain FSH). The theory is that by lowering FSH levels with estrogen, the ovary will respond when high doses of FSH are added(in the form of the fertility injections). It sounds reasonable, however there is no literature to support these claims, i.e. there is no evidenced based medicine.

References:

  • Licciardi FL, Liu HC, Rosenwaks Z. Day 3 estradiol serum concentrations as prognosticators of ovarian stimulation response and pregnancy outcome in patients undergoing in vitro fertilization. Fertil Steril. 1995 Nov;64(5):991-4.
  • Bancsi LF, Broekmans FJ, Eijkemans MJ, de Jong FH, Habbema JD, teVelde ER. Predictors of poor ovarian response in in vitro fertilization: a prospective study comparing basal markers of ovarian reserve. Fertil Steril 2002; 77(2):328-36.
  • Broer AL, Mol BWJ, Hendriks D, Broekmans FJM. The role of antimüllerian hormone in prediction of outcome after IVF: comparison with the antral follicle count. Fertil Steril 2009; 91(3):705-14.
  • Toner JP, Philput CB, Jones GS, et al. Basal follicle-stimulating hormone level. Fertil Steril 1991; 55:784.

High FSH: an Excuse to Send Patients Away

It is really hard, if not impossible to become pregnant with a high FSH level. The number of quality eggs is just too low. But some people defy the odds.
Many fertility centers don’t like to treat women with elevated FSH levels because the odds of pregnancy are lower, thus lower statistics, and it’s frustrating for the physician to deal with failure. But I believe there needs to be a little more wiggle room when it comes to FSH levels.
Some doctors say once there is one elevated FSH, it’s over. This is not true. FSH levels go up and down from cycle to cycle(could be by a few points), so one elevation, along with other levels that are in the normal range, does not mean sterility. Therefore, I always repeat levels when the first reading is high. (I do have to say that repeatedly high levels are a very bad sign and should not be ignored.)
Here are today’s examples.
A 43 year old woman came back after having her first baby with IVF. Her FSH was 14.6, over the 12.4 limit at NYU. I repeated the level and it was 12.1. We started an IVF cycle with a level of 12.8, slightly over my limit, but I felt there was wiggle room and wanted to give her a shot. She had a successful cycle.
Unfortunately, not all of the stories are as hopeful.
A 39 year old had a day 3 FSH level of 10. This is borderline but good enough. I started her IVF cycle with a level of 12.5, very slightly over my limit. Despite 7 days of high dose fertility drugs, she didn’t make one egg and was cancelled.
The point I want to emphasize is that FSH is a far from perfect predictor of outcome. A low level does not guarantee pregnancy. An elevated level may be bad news, however women should not be overly discouraged when a single blood test shows a high level. Repeating the test is very important, as is making attempts at pregnancy when the levels are borderline.
Next time I want to clarify the estradiol level and give my opinion on protocols to lower FSH levels.

References:

  • Licciardi FL, Liu HC, Rosenwaks Z. Day 3 estradiol serum concentrations as prognosticators of ovarian stimulation response and pregnancy outcome in patients undergoing in vitro fertilization. Fertil Steril. 1995 Nov;64(5):991-4.
  • Bancsi LF, Broekmans FJ, Eijkemans MJ, de Jong FH, Habbema JD, teVelde ER. Predictors of poor ovarian response in in vitro fertilization: a prospective study comparing basal markers of ovarian reserve. Fertil Steril 2002; 77(2):328-36.
  • Broer AL, Mol BWJ, Hendriks D, Broekmans FJM. The role of antimüllerian hormone in prediction of outcome after IVF: comparison with the antral follicle count. Fertil Steril 2009; 91(3):705-14.
  • Toner JP, Philput CB, Jones GS, et al. Basal follicle-stimulating hormone level. Fertil Steril 1991; 55:784.

The First of a Few About FSH Levels

For today I will explain what the day 3 FSH levels are, and in upcoming blogs I will talk more about FSH, and Estradiol, and then give some examples from my practice. Its not a very exciting subject, but I really want people to understand because so much is written about it and it effects so many women. I’ll start by saying the subject is not easy for anyone to completely understand because in the real world there are always exceptions, some of which I will show you.
FSH stands for Follicle Stimulating Hormone. Hormones are chemicals in your body that are made in one place and are used in another. FSH is made in the pituitary gland, which is a small gland found near the base of the brain. The pituitary makes other hormones. One controls the thyroid gland(TSH), another the adrenal gland(ACTH), and there are a few others.
As the name implies FSH gets the ovaries to work. Inside the ovary there are many many tiny follicles. A follicle is a fluid filled cyst that has one egg inside. The follicle starts as a microscopic structure, but FSH causes the fluid around the egg to increase so that the follicle becomes a cyst, and that’s what we see on ultrasound. In a normal cycle the follicle eventually bursts releasing the egg at ovulation. By the way, FSH is the same hormone that stimulates sperm production in men.
If the ovary has many eggs, the FSH in a woman’s blood is low because the body doesn’t need to work hard to get a normal ovulation. If the egg number is low, the body needs to work harder to get ovulation, so it increases the amount of FSH in an effort to push the ovaries. A high FSH means the egg number is reduced, sometimes to levels so low that pregnancy is not possible. What is a good level? Well that depends on each individual lab and IVF program. For most centers, anything over 12 is considered not so good. In fact, some centers will not give fertility treatment to those over 12 because the odds of pregnancy become very low. But as you will see later, not always impossible. Please return in a couple of days because there is much more that needs to be said on this subject.