Do Antibiotics Before Conception Affect Fertility?

Is there a connection between antibiotics taken before conception and adverse outcomes, such as reduced fertility, miscarriages, and congenital malformations?

A meta-analysis published in the journal eClinical Medicine suggests a potential link between antibiotics taken before conception and negative outcomes, such as reduced fertility, miscarriages, and congenital malformations. However, a German expert in reproductive toxicology warned against drawing false conclusions.

“It would be fatal if women who want to have children refused necessary antibiotic treatment because they are afraid of infertility, miscarriages, and malformations,” said Wolfgang Paulus, MD, from the Reproductive Toxicology Advisory Center at the University Women’s Hospital in Ulm, Germany. In an interview with Medscape’s German edition, the expert criticized not only the authors’ conclusions but also the selection of studies included in the meta-analysis.

Confusion Over Use and Exposure

The meta-analysis, conducted by Bekalu Kassie Alemu, PhD, and colleagues from the Department of Obstetrics and Gynecology at The Chinese University of Hong Kong, Hong Kong, China, included 15 studies involving over 1.2 million women to examine how preconception antibiotic use affects fertility and pregnancy outcomes. In most studies (n = 11) that were included in the meta-analysis, fertility was examined as an endpoint, primarily in infertile women. One study involved Danish pharmacy employees who handled antibiotics at work.

“Not only was the therapeutic use of antibiotics not examined in this study, but the biological plausibility is completely lacking in this context,” Paulus noted.

The possible effects of preconception antibiotics on miscarriages were investigated in four studies, while two studies focused on congenital malformations as an endpoint.

Mixed Findings on Infertility

Regarding infertility, the authors reported abnormalities in macrolides and sulfonamides. Women who had received macrolide antibiotics, such as azithromycin, before conception showed a 35% reduction in fertility rates.

However, Paulus questioned whether this was solely because of macrolides. “Macrolide antibiotics are typically used for chlamydia, and chlamydia infection is a significant factor in women with unmet fertility desires,” he explained. Often, the chlamydia has already caused damage, such as inflammatory processes in the fallopian tubes, contributing to infertility that cannot be resolved by administering antibiotics.

The meta-analysis also showed that women who received sulfonamide before conception had a 2.35-fold increased likelihood of infertility. However, this association is not always one-sided. The results for tetracyclines were heterogeneous; while chlortetracycline appeared to increase the risk for infertility, exposure to oxytetracycline appeared to decrease it.

Treatment with oxytetracycline and beta-lactam antibiotics (except penicillin G) was associated with a 64% lower likelihood of infertility. The authors also found that fluoroquinolone antibiotics were associated with a 13% lower likelihood of infertility.

Miscarriage and Malformation Risks

Alemu and colleagues found a significant association between the use of antibiotics before conception and adverse pregnancy outcomes, showing a 34% increased risk for miscarriages and an 85% higher risk for congenital malformations with the use of trimethoprim during preconception. These findings highlight the need for caution regarding antibiotic use in women who are planning to conceive.

“Most antibiotics have half-lives of only a few hours. Therefore, antibiotics administered before conception can hardly have a direct effect on embryonic development,” Paulus noted. He pointed out that extensive data exist on most antibiotic classes included in this meta-analysis regarding childhood anomalies when used during the sensitive phase of organ development. These data do not indicate an increased risk for malformation. Therefore, the increased risk for malformations due to exposure before conception seems less plausible.

Alemu and colleagues assumed that antibiotics might negatively affect female reproductive health by disrupting the gut microbiome. The reasons for the reduced risk for infertility associated with beta-lactams and fluoroquinolones require further investigation. They reach a significant conclusion: “Preconception antibiotics exposure in females increases the risk of infertility, miscarriage, and congenital anomalies.” However, differences exist between the antibiotic classes. While the risk for infertility, spontaneous miscarriages, and congenital malformations increases with the use of macrolide antibiotics, sulfonamides, and trimethoprim, it decreases with the use of beta-lactams and fluoroquinolone antibiotics.

Expert Disagreement

“It is conceivable that the use of antibiotics damages the physiological environment, such as in the vaginal area. This may allow unwanted microbes to establish themselves, leading to more adverse outcomes such as infertility and miscarriages,” Paulus acknowledged.

Disruption of the microbiome due to antibiotic therapy could also result in a deficiency in relevant vitamins and trace elements (eg, folic acid), which could contribute to organogenesis disorders. Therefore, it may be beneficial to stabilize the gut and vaginal flora using probiotics after antibiotic treatment.

However, Paulus disagrees with the study conclusions. First, the studies included in the meta-analysis, which were largely observational, did not allow for the direct effect of antibiotics on the examined outcomes. Second, “quinolone antibiotics are highlighted as positive here, as if they were less problematic for patients trying to have children,” he criticized.

Quinolone antibiotics are generally “frowned upon,” regardless of whether the patient wants to have children, as they can cause damage to the tendons, muscles, joints, and nervous system. They are currently used only as reserve medications.

“Quinolone antibiotics should not be administered during pregnancy, as they have already caused problems in animal studies, and they should not be used before pregnancy because of their side-effect profile,” Paulus stressed.

Serious Consequences

Paulus clarified: “The message must not be that women trying to conceive should avoid antibiotics. This applies to treating bacterial infections regardless of fertility desires, as well as for women trying to conceive who have problematic pathogens found in vaginal swabs.”

In these cases, antibiotic treatment is appropriate, and there should be no fear of adverse effects on fertility or pregnancy outcomes. “If antibiotics are not given and the infection worsens, the patient will be even less likely to conceive successfully.”

This story was translated from Medscape’s German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.