Clomiphene For Women Over 35: A Bad Idea

29 May
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Clomiphene citrate (Clomid) is by far the most commonly used fertility drug in the world. Used in the right circumstances and with appropriate application, it can be and is effective in assisting conception.

Ideally the use of clomiphene should be confined to younger women (under 35 years) who have normal “ovarian reserves” (as evidenced by normal day-3 FSH, Inhibin B or antimulerian hormone[AMH] levels) and accordingly are most likely to respond by producing the multiple follicles (more than 3) necessary to override the “antiestrogenic” effects of clomiphene (see below). If used for longer than 3 consecutive months, clomiphene is not only ineffective, but actually starts to function as a “relative” contraceptive! This is a shocking revelation to many women that I consult with who have often done 6 or more consecutive cycles of Clomiphene without success.

Few realize that the rate of conception with clomiphene therapy is about 1/3 lower than the natural fertility rate for any given age and about 25% lower than when gonadotropin stimulation is used. This problem increases significantly with advancing age. Consider the fact that in women under 35 years, the pregnancy rate with clomiphene treatment is about 10% per cycle, about 5% between 35 and 40 years and 2% after age 40. Here are a few reasons why:

  1. Clomiphene through its “anti estrogenic effect” tricks the hypothalamus into thinking that estrogen levels are low. In response, the pituitary gland releases an exaggerated amount of follicle-stimulating hormone (FSH), which stimulates development of the follicles, ultimately resulting in ovulation. The growing follicles secrete estrogen into the bloodstream, thus closing the feedback circle that the hypothalamus initiated in response to the anti-estrogen properties of Clomiphene. Unfortunately however, at the same time the pituitary also releases large amounts of LH which causes the ovary to produce large amounts of the male hormone testosterone. In high local concentrations, testosterone can compromise egg quality and thus ultimately the chance of having a baby. The older the woman, the greater this adverse effect of clomiphene will be.

  2. Clomiphene’s anti-estrogenic effects often manifest as an over-thin uterine lining that is incapable of supporting a healthy pregnancy, thickening of the cervical mucus, making sperm migration via the uterus to the awaiting egg in the fallopian tube difficult or impossible. This antiestrogenic effect will invariably build to such a degree over 3 consecutive back-to back cycles of clomiphene therapy (that regardless of age or “ovarian reserve”) most women will manifest with such effects by the 4th month of back-to-back cycles of stimulation. This is why no one using clomiphene should do more than three consecutive cycles of treatment without taking at least a break in therapy. Fortunately, the cessation of Clomiphene treatment for only one (1) month is usually sufficient to completely reverse such highly undesirable side effects. The same anti-estrogen effects can occur with the very first clomiphene treatment cycle. This usually happens in women over 35 years and those with elevated FSH levels (poor responders) who cannot produce enough follicles that would produce sufficient estrogen to overcome the anti-estrogenic effects of clomiphene. When this happens or when the woman fails to conceive following (at most) 3 cycles of clomiphene stimulation, it is time to move on to a different method of treatment.

  3. Twenty percent of clomiphene cycles are associated with trapped ovulation (LUF syndrome). This means that in spite of hormone changes suggesting that ovulation has occurred, the egg remains trapped in the ovary. Obviously this is not condusive to the establishment of a successful pregnancy. The above serves to explain why I strongly hold that Clomiphene should not be prescribed to women over 35 years of age, never to women with diminished ovarian reserve or women over 40 years, and should be avoided in IVF(alone or in combination with gonadotropins). The results are simply too poor to validate such practices.

35 Comments

  • Hema David says:

    I am a 40 yr old woman. Had my first child at 35, with assistance. I was given Clomid, with Ovidrel injection, and an IUI. And boom, first time around got pregnant. That of course is when I had good insurance. Now that we are looking to have another, me being 40, and my husband getting close to 48, with no good insurance to cover the expensive treatment of infertility; I’ve decided to take matters into my own hands by attempting to do the same thing I did the last time with doctors, except on my own. I have the medications I need, but now I’m concerned after reading that Clomid can have a negative or no effect on a 40 yr old or over. That’s discouraging! And after reading a testimony about how Clomid worked for a 42 yr old it seems like it’s still possible. I still do however want to get your opinion on taking Clomid, since I took my first dose last night. Whether I should continue, and if I continue when I should take the ovidrel shot. I was hoping to do use a syringe and inseminate myself with my husband’s sperm during this time. Pls let me knw your opinion. Thank you!

    • Geoffrey Sher says:

      My website has changed. The new site is at http://www.sherIVF.com where I host and populate new and updated blog articles . The blog can also be accessed directly by going to http://goo.gl/4hvjoP. I now only respond to posts on this new site.

      To find and follow updated and new blog articles and to post questions or comments, please use this new venue. I promise to respond promptly.

      In the interim, please re-post this question or comment on my new website-blog.

      Geoff Sher

  • Tina says:

    Dr. Sher, I want to relay my experience because it contradicts your statements, and I think it’s important for women to know my story.

    At 40.5 years old, I embarked upon a series of three back-to-back rounds of IVF. I used Gonal-F and donor sperm, and I had large quantities of eggs retrieved (around 20 each time). However, the quality of my fertilized embryos by day 5 was really bad, and I failed to get pregnant.

    I then had two rounds of IUI, again with Gonal-F and donor sperm, and they did not result in pregnancy.

    I then had another round of IVF with Gonal-F and donor sperm. Still no pregnancy.

    Then, my doctor, thinking that the odds of me getting pregnant were slim to none, had me do two more rounds of IUI, but on very high doses of Gonal-F. Both times, I had a total of ten mature follicles. Still no pregnancy.

    By this time, I was 42 years old. I told the doctor that although I was considered “old,” there was NO WAY that 100% of my eggs are bad. There HAVE to still be some good eggs inside me, and I want to keep trying until we find one. My doctor decided to put me on clomid for one round of IUI. No pregnancy.

    Then, my doctor decided to put me on clomid for the beginning of the cycle, and to have me inject follistim during the last few days of the cycle. I had four mature follicles. BINGO, I got pregnant on that round of IUI.

    Some people might think that I just finally got lucky after trying a million times, but I have to wonder if Gonal-F jus didn’t agree with my system. Regardless, at age 42, clomid worked for me when Gonal-F never did. I am now 23 weeks pregnant with a 100% healthy baby girl.

    • Geoffrey Sher says:

      Hi Tina,

      I am so pleased for you…and yes you were lucky because the chance of pregnancy on clomiphene at 42y is about 2%. It goes to show however ever, that “man proposes while G-d disposes”.

      May you and you family to be…thrive, be happy and thankful for His grace!!

      Geoff Sher

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