Why Am I Ovulating on Clomid® but Not Getting Pregnant?

By Dr. Kenosha Gleaton, OBGYN and fertility expert

If you’ve taken the step to try out ovulation induction medications, it can be frustrating not immediately seeing a positive pregnancy test. Let’s talk about the use of Clomid® when trying to conceive (TTC) and why you may not be getting pregnant right away.

Understanding Clomid®: How it works to induce ovulation

Clomiphene citrate is a medication prescribed to help induce ovulation. A common brand name of clomiphene is Clomid®. This drug is a nonsteroidal triphenylethylene derivative estrogen agonist-antagonist, which is a very complicated way of saying it helps to induce ovulation by tricking the body into believing estrogen levels are low. [1] This triggers a hormonal response that causes the body to grow and release one or more eggs. Clomiphene is often prescribed to those struggling to conceive because of irregular periods or anovulatory cycles (cycles where you don’t ovulate). [1]

The role of ovulation in conception

Regular ovulation is key to getting pregnant. There is already a very small window of time where conception is possible (around 12 to 24 hours) so it’simportant that anyone trying to get pregnant knows their fertile window and confirms that ovulation is actually happening with ovulation tests. [2] When an egg is released, it has about a day to meet up with sperm and become fertilized. [2] If ovulation isn’t occurring regularly or at all, the chances of getting pregnant are going to be very low. This is where ovulation induction can help.

Success rates of clomiphene citrate

Medications such as Clomid® are usually very effective at stimulating the ovaries and causing ovulation to occur. One study found that 80% of anovulatory women successfully ovulated after using Clomid®. [3] Even thoughClomid® is often used to help women with PCOS ovulate, it is possible to not ovulate on Clomid®, which is sometimes seen in those with polycystic ovary syndrome (PCOS) or other conditions. [1] While there are relatively high ovulation rates on clomiphene, ovulation alone does not guarantee pregnancy. Pregnancy rates on clomiphene citrate range from about 10-20% per cycle, increasing to around 60% after six cycles. [3] Want to learn more? Read the Complete Guide to Clomiphene Citrate

Why pregnancy may not be occurring

There are a number of reasons that you may be ovulating on clomiphene without getting pregnant. For starters, there are many other factors that contribute to fertility outside of anovulation. There could be structural problems making it difficult for sperm and egg to meet inside the reproductive tract, there could be problems with male fertility, underlying conditions, etc. [4] Let’s break these down.

Structural problems

Any physical barriers in the anatomy of the reproductive system may make it difficult to conceive, even if ovulation is occurring. Potential structural problems could include a blocked cervix, fibroids, blocked ejaculatory duct, scar tissue from conditions such as endometriosis or untreated STIs, abnormally formed organs, and more. [4] These can be ruled out through x-rays or ultrasounds, which your provider may recommend if you’re still having trouble getting pregnant after about six months to a year depending on your age and background.

Male factor infertility

There could also be problems with male factor infertility. This may include decreased sperm production, poor sperm motility, sperm morphology, etc. [4] You can get more information in the Urologist’s Guide to Male Fertility. One way to rule out some issues with sperm is by completing a semen analysis through your healthcare provider or an at-home testing kit.

Underlying conditions

Not only is ovulation important, but the uterus must also be in good shape to support a pregnancy. Underlying conditions can make it more difficult for a fertilized egg to implant into the uterine wall or for a pregnancy to progress. [4] Other potential conditions may include PCOS, endometriosis, thyroid conditions, etc. [4] These can all impact hormones and organs necessary for a healthy pregnancy.

This isn’t a comprehensive list of potential problems, and the frustrating reality is that there sometimes isn’t an explanation for infertility. If you have been taking ovulation induction medications and aren’t getting pregnant, know that you aren’t alone. A literature review found that although 73% of people did ovulate on Clomid, only 36% actually achieved pregnancy. [5]

Other fertility treatments: When to consider alternatives to Clomid®

Fertility treatment recommendations will vary on a case by case basis, but generally providers don’t encourage more than six cycles of ovulation induction medications before suggesting a different route. [6] If you haven’t successfully ovulated on Clomid®, your provider may first suggest increasing the dosage or trying an alternative drug such as letrozole or injection gonadotropins. [1] Letrozole is a medication used to treat breast cancer, but is often used off-label for ovulation induction, especially in those with PCOS. [7-8] Learn more about clomiphene citrate vs letrozole.

Outside of ovulation induction medications, there are fertility treatments such as intrauterine insemination (IUI), in vitro fertilization (IVF), and more. Deciding which one is right for you may require a more lengthy conversation between you, your partner, and your healthcare provider. Just know that there are a lot of options available if ovulation induction medications don’t seem to be working for you. [4]

Maximizing your chances of conception

Whether you’re on Clomid®, exploring other fertility options, or you’re trying to conceive without the use of medications or treatments, there are a few things you can do to increase your chances of getting pregnant. First, it’s important to prioritize your overall health. Try to stay within a healthy weight range for your height, eat a balanced diet, move your body, and pay attention to your lifestyle habits. [4,9] If you’re TTC, The American College of Obstetrics and Gynecology (ACOG) recommends you take a prenatal multivitamin. [9] This is a great way to ensure you’re getting all of the vital nutrients needed for pregnancy such as folate, DHA, iron, calcium, and more. [10]

Another way to maximize your chances of conception is to time sex according to your fertile window. There is a short period of time after ovulation for fertilization and implantation to occur. [2] Tracking ovulation through ovulation tests and ovulation kits, basal body temperature, or cervical mucus is a great way to improve your chances.[4]

Another way to support the conception process is to ensure you’re using a sperm-friendly lubricant. Some lubricants contain ingredients you may want to avoid for the sake of fertility and vaginal health. [11-12] The FDA has cleared some lubricants to be fertility friendly, meaning they’re compatible with sperm, egg, and embryos. [13]

Shop Fertility Products

To summarize

If you’ve confirmed that you are ovulating on clomiphene citrate, but have not gotten pregnant, there are a few possible explanations. First, you should ensure you’re timing sex correctly around ovulation. The chances of conceiving peak the day or two prior to ovulation, so make sure you’re using ovulation tests and tracking your menstrual cycles to get the best idea of your fertile period. [2,4]

Structural complications may make it difficult for sperm to leave the ejaculatory duct, or perhaps you have fibroids or scar tissue blocking the way for sperm and egg to meet. [4] You may also have an underlying condition such as PCOS or endometriosis making it more difficult to conceive. [1,4] A semen analysis may also help rule out any problems with sperm parameters. It may take several cycles before you’re able to conceive on Clomid®, although pregnancy isn’t a guarantee. If you’ve completed more than six cycles of ovulation induction medications, it’s recommended that you speak with a healthcare provider about exploring a different fertility treatment option. [3]

References:

1. Mbi Feh MK, Wadhwa R. Clomiphene. [Updated 2022 Jun 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559292/
2. Sung S, Abramovitz A. Natural Family Planning. [Updated 2022 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546661/
3. Seyedoshohadaei F, Zandvakily F, Shahgeibi S. Comparison of the effectiveness of clomiphene citrate, tamoxifen and letrozole in ovulation induction in infertility due to isolated unovulation. Iran J Reprod Med. 2012;10(6):531-536.
4. Carson SA, Kallen AN. Diagnosis and Management of Infertility: A Review. JAMA. 2021;326(1):65-76. doi:10.1001/jama.2021.4788
5. Roy Homburg, Clomiphene citrate—end of an era? a mini-review, Human Reproduction, Volume 20, Issue 8, August 2005, Pages 2043–2051, https://doi.org/10.1093/humrep/dei042
6. OVULATION INDUCTION (OI). NHS. Accessed April 2023. URL.
7. Costello M, Garad R, Hart R, et al. A Review of First Line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome. Med Sci (Basel). 2019;7(9):95. Published 2019 Sep 10. doi:10.3390/medsci7090095
8. Understanding Unapproved Use of Approved Drugs "Off Label". FDA. Updated 02/05/2018. URL.
9. Good Health Before Pregnancy: Prepregnancy Care. ACOG. Last reviewed: December 2021. URL.
10. Dou JF, Middleton LYM, Zhu Y, et al. Prenatal vitamin intake in first month of pregnancy and DNA methylation in cord blood and placenta in two prospective cohorts. Epigenetics Chromatin. 2022;15(1):28. Published 2022 Aug 2. doi:10.1186/s13072-022-00460-9
11. Smith KW, Souter I, Dimitriadis I, et al. Urinary paraben concentrations and ovarian aging among women from a fertility center. Environ Health Perspect. 2013;121(11-12):1299-1305. doi:10.1289/ehp.1205350
12. Shin B, Kwon JA, Park EK, et al. Prenatal Exposure to Parabens Affects Birth Outcomes through Maternal Glutathione S-Transferase (GST) Polymorphisms: From the Mothers and Kids Environmental Health (MAKE) Study. Int J Environ Res Public Health. 2021;18(6):3012. Published 2021 Mar 15. doi:10.3390/ijerph18063012
13. Product Classification. FDA. Last Updated: 04/10/2023. URL.