Reproductive health concerns are a common challenge faced by many women, including struggles with conception or pregnancy, often due to underlying medical complications or the natural effects of aging. With a variety of medical treatments available, pharmacogenetic testing can help select the best course of action based on your specific needs and genetic profile. As women get older, fewer eggs remain in their ovaries, and fertility treatment success rates tend to go down. When ovarian reserve is low, every decision in an IVF cycle is crucial, especially medication choice, both for the success of the treatment and most importantly for your own health and safety.  DNA testing can predict how someone might respond to specific fertility medications, indicating their effectiveness and potential risk of complications.

Treating health conditions that reduce fertility

Before starting fertility treatment, women should undergo a baseline health assessment to identify the root causes of infertility. The use of blood work for hormone levels, such as anti-Müllerian hormone (AMH), Follicle Stimulating Hormone (FSH), and estradiol, along with an ultrasound, helps assess ovarian reserve and uterine health. Depending on the underlying concern, various medications or treatments may be prescribed. Weight-loss medications such as Mounjaro, Ozempic or Wegovy can help women with excess weight and polycystic ovary syndrome (PCOS) improve hormonal balance and restore fertility. Similarly, endometriosis is a common condition that may require drug therapy or surgery.

Different types of genetic tests are essential for successful fertility treatment:

• Carrier screening: tests parents to assess potential inherited condition risks
• Pharmacogenetics: predicts the mother’s medication response and risk of drug side effects
• Preimplantation genetic testing (PGT): screens embryos for genetic abnormalities to help choose which embryo to transfer

Different types of ovarian stimulation

Ovarian stimulation is a part of IVF where hormone medications encourage the ovaries to mature more than one egg in a cycle. Many people take daily injections for about 10–12 days, plus another medication to prevent ovulation too early. The goal is to collect multiple mature eggs, which can increase the chance of creating embryos.

There are several hormonal treatment options that your doctor will consider, depending on age, ovarian reserve, previous IVF responses, PCOS status, and personal preferences. It is essential to know that these hormonal therapies can increase the risk of deep vein thrombosis and stroke, and ovarian hyperstimulation syndrome (OHSS), which affects about 5-7% of IVF cycles.

Standard stimulation: involves injections of recombinant or urine-derived FSH and Luteinizing Hormone (LH) to stimulate egg production, with a GnRH antagonist added mid-cycle to prevent premature ovulation. This protocol is shorter (10-12 days) and carries a lower risk of ovarian hyperstimulation. Variations in several genes encoding hormones (FSH, LHβ) and their receptors (FSHR, LHCGR) can affect the response to hormonal stimulation and inform the choice of protocol and required treatment duration.

Minimal stimulation (Mini-IVF): women with moderate ovarian reserve can try induction with clomiphene or letrozole, using minimal gonadotropins. This protocol produces fewer eggs but is gentler on the body, less expensive, and carries a lower risk of overstimulation and complications.

Natural cycle IVF: a treatment that aims to collect a single egg produced during a woman’s normal monthly cycle without the use of stimulating hormones. This involves the lowest medication exposure and may be considered in select situations.

Why pharmacogenetic testing matters before ovarian stimulation

A pharmacogenetic test, such as Pillcheck, can be used for women considering clomiphene. Clomiphene is primarily converted to its active form by the liver enzyme CYP2D6. Women with low enzyme activity are not expected to respond to this medication. On the other hand, women who are ultrarapid metabolizers are at higher risk of ovarian hyperstimulation. Therefore, Pillcheck can confirm whether clomiphene is an appropriate option.

A pharmacogenetic test can inform about the risk of thrombosis and pregnancy loss

IVF and pregnancy naturally increase blood-clotting factors. For most people, the absolute risk of a serious blood clot remains low, but it can be higher with specific inherited genetic variants, especially Factor V Leiden (F5) and Prothrombin G20210A (F2).

A meta-analysis of prospective cohort studies found that women with Factor V Leiden had a 52% higher risk of pregnancy loss (absolute risk 4.2% vs 3.2%), which is found in up to 40% of pregnancy-related blood clots in a vein. Women with these genetic risk factors may prefer natural cycle IVF or may require prophylaxis with low-dose blood thinners to reduce the risk of complications during hormonal stimulation and pregnancy.

Summary

Genetics can play a critical role in the safety and success of fertility treatment. Pharmacogenetic testing is recommended for women with:

• A personal history of venous thrombosis
• A family history of stroke or known higher-than-average tendency to form blood clots
• Previous severe pregnancy complications, including preeclampsia, placental abruption, and late or recurrent pregnancy loss.
• Poor (low) response to clomiphene
• Previous experience with ovarian hyperstimulation

References

Ghobadi C et al., CYP2D6 is primarily responsible for the metabolism of clomiphene Drug Metab Pharmacokinet. 2008;23(2):101-5.

Conforti A et al., Impact of gonadotropin genetic profile and ovarian reserve on controlled ovarian stimulation: data from prospective cohort of the GENOCS trial Front Endocrinol (Lausanne). 2025 Aug 22:16:1601803.

Farooqui AB et al., Cerebral Venous Thrombosis and Hypercoagulability Associated With In Vitro Fertilization Stroke. 2021 Aug;52(9):e554-e557.

Rodger Ma et al., The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies PLoS Med. 2010 Jun 15;7(6):e1000292.