Longer Menstrual Cycles Linked to FET Pregnancy Risks

Key Takeaways

• Gestational diabetes occurred in 25.6% of Shanghai women without PCOS who delivered singleton live births after FET and had cycles of at least 36 days, with significantly higher adjusted odds than in the 28–31-day group.
• Gestational hypertension occurred in 12.2% of the at-least-36-day group, which had significantly higher adjusted odds than the 28–31-day group.
• Gestational hypertension was associated with significantly higher adjusted odds for 32–35-day cycles than for 28–31-day cycles.
• GDM was associated with significantly lower adjusted odds for cycles of 27 days or fewer than for 28–31-day cycles.

For patients undergoing frozen embryo transfer (FET), it remains uncertain whether prepregnancy menstrual cycle length relates to gestational diabetes mellitus (GDM) or gestational hypertension in the absence of polycystic ovary syndrome (PCOS). Their cycle histories can be assessed alongside subsequent pregnancy outcomes to explore this relationship.

Investigators assembled a retrospective, single-center Ruijin Hospital frozen embryo transfer cohort at its Reproductive Medical Center in Shanghai, covering transfers from January 2015 through December 2022. The analysis included 2,543 patients without PCOS who underwent FET, delivered a singleton live birth, and had complete cycle, covariate, and outcome records. Prepregnancy cycles were classified as 27 days or fewer, 28–31 days, 32–35 days, or at least 36 days; 28–31 days served as the reference. Adjusted logistic models examined GDM and gestational hypertension while accounting for age, body mass index (BMI), parity, infertility factors, fertilization and transfer parameters, and embryo characteristics. Cycle length was an observed characteristic, not an assigned intervention.

Among the selected singleton live births, patients with cycles of at least 36 days had higher adjusted odds of GDM than those with 28–31-day cycles. The adjusted odds ratio (aOR) was 1.54, with a 95% confidence interval (CI) of 1.14–2.09. Patients in the shortest-cycle group had significantly lower adjusted odds of GDM than the reference group. These associations do not describe the likelihood of achieving a live birth after FET.

Patients with cycles of at least 36 days also had higher adjusted odds of gestational hypertension than those with 28–31-day cycles (aOR 1.60; 95% CI 1.05–2.42). The 32–35-day group had significantly higher adjusted odds of gestational hypertension than the reference group. Other assessed pregnancy complications and birth outcomes did not differ significantly across the cycle categories, according to the investigators.

Because the retrospective cohort included only FET pregnancies ending in singleton live birth, its associations cannot establish causation or necessarily extend to fresh transfers, unsuccessful FET attempts, or other pregnancies. Self-reported menstrual histories and residual confounding remain considerations despite covariate adjustment; baseline insulin and lipid profiles were unavailable. An exploratory subgroup with cycles of at least 60 days was very small and had elevated but statistically nonsignificant estimates for both outcomes. The observed pattern does not establish a metabolic mechanism or show that changing cycle length would change pregnancy outcomes.

Aihaiti and colleagues concluded that longer prepregnancy cycles were associated with GDM and gestational hypertension among patients without PCOS whose FET pregnancies ended in singleton live births. They called for larger prospective studies to validate the associations.

Clinician Questions

Which conditions excluded patients from the menstrual-cycle analysis of singleton births after frozen embryo transfer?

For the menstrual-cycle analysis of frozen embryo transfers ending in singleton live birth, investigators excluded patients with polycystic ovary syndrome; preexisting diabetes, hypertension, hyperlipidemia, pituitary disease, or thyroid disease; uterine factor infertility; or decreased ovarian reserve, including donor-oocyte cases.

What counted as a prolonged prepregnancy menstrual cycle in the frozen embryo transfer cohort?

Among patients undergoing frozen embryo transfer at Ruijin Hospital in Shanghai, the investigators’ prolonged-cycle category included self-reported cycles of at least 36 days, cycles too irregular to estimate, and physician-diagnosed oligomenorrhea. This was an exposure classification, not a treatment.