Does Cotrimoxazole Affect Fertility? A Comprehensive Pharmacological Review

October 18, 2025 •

4 min read

Multiple animal studies have demonstrated that cotrimoxazole can have adverse effects on fertility by impacting sperm quality and ovarian function. This article explores the question: Does cotrimoxazole affect fertility, its mechanisms, and considerations for those trying to conceive.

Quick Summary

An in-depth analysis of how the antibiotic cotrimoxazole impacts male and female reproductive health, its mechanism via folate antagonism, and important safety considerations before and during pregnancy.

Key Points

Adverse Effects on Sperm: Studies show cotrimoxazole significantly decreases sperm count, motility, and viability in male rats.
Impacts Egg Quality: In female rats, the drug reduces the maturation of oocytes (eggs) and can cause structural damage to ovarian tissue.
Folate Antagonism is Key: The primary mechanism is the drug's interference with folic acid synthesis, a process crucial for rapidly dividing cells like sperm and eggs.
Pre-Conception Risk: Use of trimethoprim (a component of cotrimoxazole) in the 12 weeks before conception is linked to a higher risk of birth defects.
Pregnancy Concerns: It is an FDA Pregnancy Category D drug and should be avoided in the first trimester and late pregnancy due to risks of birth defects and miscarriage.
Folic Acid Supplementation: Co-administration of folic acid has been shown to partially reverse the negative reproductive effects in animal studies.
Consult a Doctor: Individuals trying to conceive should discuss cotrimoxazole use with their healthcare provider to consider alternative treatments.

What is Cotrimoxazole?

Cotrimoxazole is a combination antibiotic medication composed of sulfamethoxazole and trimethoprim, prescribed for various bacterial infections such as UTIs and certain types of pneumonia. It works by inhibiting bacterial folic acid synthesis, a vital process for their growth. While humans get folic acid from their diet, bacteria must produce it internally, making the drug selectively toxic to bacteria. However, this interference with folate pathways, known as folate antagonism, raises concerns about its impact on human reproductive health.

The Mechanism: Folate Antagonism and Reproduction

Folic acid is essential for cell division and DNA synthesis in humans, particularly for rapidly dividing cells like sperm and egg cells. Cotrimoxazole's components block different stages of folic acid synthesis. Trimethoprim inhibits the enzyme dihydrofolate reductase (DHFR), which is crucial for converting folic acid to its active form. This inhibition can lead to localized folate deficiency in human cells. Since sperm and egg development rely heavily on folate, this interference can negatively impact fertility.

Does Cotrimoxazole Affect Male Fertility?

Animal studies suggest cotrimoxazole can negatively affect male fertility. Research on rats showed a dose-dependent decrease in sperm number, motility, and viability after cotrimoxazole treatment, along with structural changes in the testes. An earlier human study also noted a drop in sperm count in some patients.

These effects are attributed to folate antagonism, as folate is vital for sperm production. Deficiency can impair sperm function and cause DNA damage. The rat study found that giving folic acid alongside cotrimoxazole offered partial protection against these negative effects. An in-vitro study also indicated that high concentrations of the drug could directly and largely irreversibly impair sperm movement.

Does Cotrimoxazole Affect Female Fertility?

Cotrimoxazole can also impact female fertility through its interference with folic acid. A study in female rats found that high doses led to fewer mature egg cells and structural abnormalities in ovarian tissue, including inflammation and necrosis.

Folate is crucial for female reproduction, affecting egg quality, maturation, and implantation. Folate deficiency can reduce the likelihood of successful pregnancy. Similar to male studies, co-administering folic acid with cotrimoxazole partially reversed the adverse effects on ovarian tissue and egg quality in rats. While antibiotics generally don't disrupt ovulation, some research links sulfonamides, like sulfamethoxazole in cotrimoxazole, to an increased risk of infertility before conception.

Comparison of Effects on Male vs. Female Fertility


Feature	Impact on Male Fertility	Impact on Female Fertility
Primary Target	Spermatogenesis (Sperm Production)	Oogenesis (Egg Maturation) & Ovarian Tissue
Key Effects	Decreased sperm count, motility, and viability. Testicular structural changes.	Decreased number of mature oocytes. Ovarian tissue abnormalities, including necrosis.
Underlying Mechanism	Folate antagonism interfering with DNA synthesis in rapidly dividing sperm cells.	Folate antagonism impacting egg quality, maturation, and implantation processes.
Mitigating Factor	Co-administration of folic acid partially reverses negative effects.	Co-administration of folic acid partially reverses negative effects.

Pre-Conception and Pregnancy Risks

Cotrimoxazole is an FDA Pregnancy Category D drug, meaning there is evidence of risk to the human fetus. Studies show this risk extends to the period before pregnancy. A large Danish study found that women exposed to trimethoprim in the 12 weeks prior to conception had double the risk of having babies with major congenital malformations, particularly heart and limb defects. This may be because the drug can deplete folate levels before the critical early stages of fetal development. Trimethoprim use in the first trimester is also linked to an increased risk of miscarriage.

Due to these risks, it is generally advised to avoid cotrimoxazole, if possible, during the first trimester and after 32 weeks of pregnancy. Anyone pregnant, planning pregnancy, or who could become pregnant should discuss cotrimoxazole use with their doctor.

Conclusion

The scientific evidence indicates that cotrimoxazole does affect fertility. Its mechanism of inhibiting folic acid synthesis poses risks to both male and female reproductive processes. For men, it can reduce sperm quality, and for women, it can damage ovarian tissue and impair egg maturation.

Given the risks, including increased chances of miscarriage and birth defects even with pre-conception use, individuals planning a pregnancy should be cautious. It is essential to discuss cotrimoxazole use with a healthcare provider. Alternative antibiotics may be safer, and for those who must take the medication, discussing folic acid supplementation is recommended, as it has shown some ability to mitigate adverse reproductive effects in studies.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.

Authoritative Link: National Institutes of Health (NIH): Trimethoprim Sulfamethoxazole

Frequently Asked Questions

The effects of cotrimoxazole on sperm parameters like count and motility appear to be linked to its interference with folic acid synthesis during treatment. While some in-vitro effects were seen as irreversible, it is generally thought that sperm production would recover after stopping the medication, though this should be discussed with a doctor.

There is no strong evidence to suggest that antibiotics, including cotrimoxazole, directly affect the hormones that regulate the menstrual cycle or ovulation. However, the drug can negatively impact oocyte (egg) quality and ovarian tissue health, which are critical for fertility.

It is generally not recommended. Studies have shown an increased risk of congenital malformations in babies born to women who took trimethoprim (a component of cotrimoxazole) in the 12 weeks leading up to conception. It's crucial to discuss family planning with your doctor before taking this medication.

Cotrimoxazole works by inhibiting folic acid synthesis, a vitamin essential for cell division and DNA production. This affects sperm and egg development. Supplementing with folic acid has been shown in animal studies to partially counteract the drug's negative effects on fertility.

Cotrimoxazole is an FDA Pregnancy Category D drug. Its use, especially in the first trimester, is associated with an increased risk of miscarriage and congenital abnormalities, such as neural tube defects, heart defects, and oral clefts, due to its antifolate effect. It should be avoided if possible.

The studies primarily focus on effects during administration. It is plausible that fertility parameters would improve after discontinuing the drug, especially since sperm production is a continuous cycle. However, one in-vitro study noted that the impairment of sperm movement was 'mostly irreversible'. The potential for long-term effects should be discussed with a healthcare provider.

If you have taken cotrimoxazole and are planning a pregnancy, it is important to speak with your doctor. They can provide guidance based on your specific situation and may recommend a waiting period before trying to conceive and ensuring adequate folic acid supplementation, given the drug's known pre-conception risks.