Clomid and PCOS

Question

I saw some information on your website but none directly relating to the question I have and was hoping you may be kind enough to help.
My question is: How does clomid use help PCOS patients conceive a healthy pregnancy? And, more specifically, how does clomid affect progesterone levels?

My background: I have PCOS and had four early term (eight week or less) confirmed miscarriages. First three micarriages were without assistance, 4th was on month three of clomid through intercourse w/ my husband. After the 4th miscarriage I was found to have PCOS due to my AMH levels and number of follicles on each ovary.

Infertility dr’s have tested me for hormone abnormalities, AMH levels, lupus, antibodies, etc. All normal tests with exception to AMH levels that are always between 6.9-13.6 and ultrasounds indicated extra follicles (10 on one side, 12 on the other).

I am a 29 year old, 5’9″ and 140lb female who is considered a ‘thin’ a-typical PCOS patient. I have had chromosome checks on both myself and husband and husband has undergone comprehensive chromosome analysis, all normal. We have even had pre-IVF testing for Hep, HIV, etc. all as you would want to find, negative.

My dr. is now recommending clomid (original dr. to prescribe w/ an obgyn).

The endocrinologist suggests that I probably have a progesterone issue where my eggs are not maturing properly and my progesterone levels are not going where they need to go. He is suggesting I do 50mg of clomid, IUI, and check progesterone on day 21 to determine if the dose needs increased.

I will say my progesterone level, even while on clomid previously was never above 15.

I just didn’t grasp how clomid correlates to increased progesterone and more successful pregnancy rates in females in situations like mine. Your website was easy to read so I was hoping your answer may clarify. Thanks.

Amanda

Answer

Last Updated: May 8, 2022
Dear Amanda,

Clomid has anti and pro estrogenic effects. It also can increase progesterone. Immediately after you take it, it suppresses estrogen. Soon after that, the pituitary gland in rebound produces higher levels of FSH. In a patient who does not ovulate, it can induce ovulation. In a patient who ovulates, but has inadequate hormone levels, it can elevate estrogen and progesterone. It might be a part of the proper treatment for you but it may not be enough.

You do not describe if you have a variant of PCOS in which you have elevated androgens (DHEA Sullfate and testosterone) or insulin resistance. There is a big spectrum of PCOS, in which some women ovulate and cycle and some do not. There are different definitions of PCOS, and not all women have all the features. I will describe a bit more complex approach to your situation that differs somewhat from what your obgyn is proposing. This draws on my training as a Medical Consultant who studied at the Pope Paul VI Institute in the FertilityCare method. Before you attempted to conceive again, it should be demonstrated that the proposed treatment would normalize your thyroid, estrogen, progesterone and insulin levels, as well as the lining of your uterus.

You should be tested for ureaplasma/mycoplasma bacteria, and you and your husband given antibiotics if this is present. The presence of this bacteria increases miscarriage risk.

With four miscarriages, you should have a thrombophilia workup for coagulation defects that cause pregnancy loss presumably through small clots in the placenta – lupus anticoagulant, anti-cardiolipin, Protein S, Protein C and others. This type of problem is treated with Lovenox, a blood thinning agent. You should have a fasting insulin level and glucose challenge test. If these are abnormal, you should go on Metformin prior to conceiving. If you are not ovulating monthly you might consider Meformin even if your insulin and glucose levels appear normal. It will reduce the risk of miscarriage in PCOS especially if begun before pregnancy and continued through the first trimester.

A thorough thyroid workup includes TSH, Free T4 and Free T3, as well as thyroid peroxidase and thyroglobuloin antibody levels. You should aim to have a TSH of below 2.5 and Free T3 in the upper third. Subtle thyroid problems, especially autoimmune thyroid conditions with elevated antibody levels, are correlated with pregnancy loss.

Learning a method of natural family planning would be helpful in your diagnosis and treatment. With the Creighton/Fertilitycare method, you would have an idea just from the charting of the adequacy of your estrogen and progesterone levels before and after treatment. If you are ovulating, your cycle should be evaluated thoroughly with estradiol levels prior to ovulation, and at least three estradiol and progesterone levels after ovulation.

It is important to get several postovulation progesterone levels. Progesterone may be adequate initially but then can fall off rapidly, causing pregnancy loss. If you only obtain one progesterone level, you may not be aware if progesterone levels are actually inadequate for part of the cycle.

You do not describe the exact regimen that is proposed, but I am guessing it will be Clomid 50 mg for five days, day 3-7 or day 5-9 of the cycle. This might make you ovulate if you are anovulatory, but has the disadvantage of drying up your mucus and making the lining of your uterus too thin from the anti-estrogenic aspect of Clomid. Because the Clomid may dry up your mucus, your doctor is proposing IUI. Some physicians use Letrozole rather than Clomid because there is a lower risk of drying up the mucus, twins or ovarian cysts.

You are obviously ovulating because you conceived three of your pregnancies without Clomid. One option if you are ovulating but have low hormone levels is to use Clomid at a smaller dose – say 25 mg day 3,4,5 of the cycle, and use HCG injections in the postovulatory phase. HCG will raise both estradiol and progesterone, and create an ideal uterine lining. HCG used in this way is given in four injections of 2000 units 3,5,7 and 9 days after ovulation. This type of regimen works very well for women who are ovulatory but with low estrogens and progesterones.

In some instances supplementary Estradiol may be needed to improve the uterine lining, or steroids such as Prednisone or Dexamethasone to lower androgens. PCOS women also benefit from a low glycemic diet, and adequate Omega 3 and B vitamins. I calculate your BMI at 20.7. A slightly higher BMI (21-25) may correlate with better estrogen levels, especially if you have very low body fat or exercise heavily. Your need to have both adequate estrogen and progesterone to maintain a pregnancy.

In any case, to prevent another miscarriage after testing, you should have a “dry run” on your treatment regimen to test your hormone levels after ovulation and and a postovulatory ultrasound to make sure your uterine lining is good before you attempt to conceive. Testing 5,7, and 9 days after ovulation should show progesterone levels of 12, 15 and 12 and estradiols of at least 100.

So I agree with you in that the regimen that is being proposed fits the typical anovulatory woman with PCOS and not you, who has had three miscarriages, one on Clomid. A more thorough workup and nuanced approach tailored to your situation would be better.

You can find a doctor trained as a FertilityCare Medical Consultant at http://www.fertilitycare.org/. This approach, in my opinion, will work better for you rather than that of your Reproductive Endocrinologist, which is oriented more toward IVF.

Mary L. Davenport, MD

Answered By:

Mary Davenport, MD, MS
Mary Davenport, MD, FACOG, an obstetrician/gynecologist from the Oakland Region of California, offers telehealth services over MyCatholicDoctor.com She graduated from Tufts University School of Medicine and completed her residency at UC San Diego. Dr. Davenport is a Fellow of the American College of Obstetrics and Gynecology, and serves on the Advisory Board of the California Association of Natural Family Planning.

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