Why Does Clomid Sometimes Fail To Achieve Pregnancy? By manara99 on July 04, 2013

Clomid (clomiphene citrate) has been available since the mid 1960’s for treatment of ovulation disorders.  It was originally being investigated as a contraceptive pill when investigators found that it enhanced the process of ovulation. Since the 1960’s there has been ample opportunity to study Clomid and its effects on fertility. Clomid works by attaching to estrogen receptors in the hypothalamus and pituitary gland.  This results in increased production of the two pituitary stimulating hormones, FSH and LH.  These two hormones act on the ovary to initiate or augment the process of ovulation by direct stimulation of the ovarian follicles.  These effects on the ovary are all beneficial.  However, Clomid also has effects on other tissues in the body which are not beneficial in terms of improving fertility potential.  Specifically, Clomid often decreases the production of cervical mucous which decreases the capacity for sperm to through the cervical canal and into the uterus.  It does not affect every woman in this way; however it is difficult to determine who will experience this adverse effect and who will not.  Daily inspection of the cervical mucous might provide some insight into this issue, but this approach would usually require multiple visits and provide less than perfect information due to the subjective nature of cervical mucous assessment.  Many clinicians address this potential problem by recommending intra-uterine insemination in patients on Clomid.  This technique involves direct placement of washed sperm into the uterine cavity and thereby diminishes the role of cervical mucous, in essence bypassing cervical mucous altogether.


In addition Clomid has been shown to thin the lining of the uterine cavity as a result of direct anti-estrogenic actions on the uterine cell lining.  Once again, while this is a known Clomid effect, for many patients it does not seem to be significant and they achieve successful pregnancy in spite of this change in the lining.  For patients who ovulate on Clomid but fail to conceive, it is suspected that this effect on the uterine lining may be the explanation.  Without a trial of using Clomid, it is nearly impossible to determine if this “thinning” of the uterine lining will prevent achievement of successful pregnancy in a given patient.


Patients often ask why Clomid is used at all in light of the known potential negative effects on processes of fertilization and implantation.  The answer is that Clomid is an oral medication and therefore easy to use.  In addition, the multiple birth rate of Clomid is 10%, consisting mostly of twins.  Alternative ovulation stimulating medications (gonadotropins) are administered only by injection, and have a 20% chance of causing a multiple birth.  Once again, most of the multiple births are twins, however an occasional “high order” multiple birth such as triplets may occasionally occur with these agents.  Therefore, in most situations Clomid or a similar oral medication remains the first line of treatment before moving on to the use of gonadotropins.  For ovulation problems, studies indicate that success will be achieved with Clomid in approximately 50% of patients, given that no other identifiable problems exist.  Because of its potential to resolve ovulation related infertility problems with reduced potential for multiple births compared to injectable gonadotropins, Clomid remains the first choice for managing most ovulation disorders.

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Dr. Louis R. Manara

Center for Reproductive Medicine and Fertility

Dr. Louis R. Manara and the Center for Reproductive Medicine and Fertility team are dedicated to helping families achieve parenthood through safe, versatile, and personalized treatment options. We are affiliated with several noteworthy organizations including:

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​If you are struggling with infertility, a professional diagnosis is the best way to explore your treatment options. Schedule your initial consultation today by contacting us online or calling us at (856) 767-0009.

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