Sporadic anovulation is not an important determinant of becoming pregnant and  time to pregnancy among eumenorrheic women: A simulation study

Elizabeth A DeVilbiss; Joseph B Stanford; Sunni L Mumford; Lindsey A Sjaarda; Keewan Kim; Jessica R Zolton; Neil J Perkins; Enrique F Schisterman

doi:10.1111/ppe.12692

Menstrual Cycle Cycle Disorders

Sporadic anovulation is not an important determinant of becoming pregnant and time to pregnancy among eumenorrheic women: A simulation study

DeVilbiss EA, Stanford JB, Mumford SL, Sjaarda LA, Kim K, Zolton JR, Perkins NJ, Schisterman EF

Published January 2021 Paediatric and Perinatal Epidemiology, 35(1), 143-152

DOI 10.1111/ppe.12692 PMID 32970334 PMC PMC7854799

RRM Academy Synopsis

Missed ovulation in regular cycles changes modeled pregnancy little

A simulation of 100,000 women with regular cycles found an occasional missed ovulation changed 12-cycle pregnancy rates only slightly. About 87 out of 100 became pregnant when missed ovulation was most common. About 91 did when it was least common. Weekly intercourse versus every other day changed the rate far more: about 60 against 89 out of 100.

Pregnant within 12 cycles: Weekly intercourse, 59.9 in 100; Every other day, 88.8 in 100. Source: DeVilbiss EA et al., 2021, PMID 32970334.

Study at a glance, simulation study: Occasional missed ovulation changed 12-cycle pregnancy rates only slightly — Study at a glance, simulation study of 100,000 women: Occasional missed ovulation changed 12-cycle pregnancy rates only slightly. Source: DeVilbiss EA et al., 2021, PMID 32970334.

Key Findings

In the simulation, cumulative pregnancy rates after 12 cycles were 86.7%, 88.8% and 90.7% at per-cycle anovulation of 14.5%, 8% and 1%. The absolute difference between 1% and 14.5% was 4.0%.
Simulated median time to pregnancy was 3 cycles at 14.5% anovulation and 2 cycles at 8% or 1%. Under a second set of assumptions, it was 3 cycles at all three rates.
Cumulative pregnancy rates after 12 cycles were 59.9% with weekly untimed intercourse, 88.8% every other day and 91.6% daily. Weekly to every other day meant an absolute difference of 28.9%.
Median time to pregnancy was 7 cycles with weekly intercourse and 2 cycles with intercourse every other day or daily.
Simulated fecundability odds ratios were 1.21 and 1.49 for 8% and 1% anovulation against 14.5%. They were 5.28 and 7.28 for every other day and daily intercourse against weekly.

Interpretation

This simulation study modeled fertile women with regular cycles, using published odds for each step from sex to pregnancy. The authors note the results may not apply to chronic conditions such as polyendocrine metabolic ovarian syndrome (PMOS), formerly polycystic ovary syndrome (PCOS). The findings support larger studies of women trying to conceive.

RRM Context

Fertility awareness methods track cervical fluid and other signs to find the fertile window. The authors cite observational studies and a trial linking timing intercourse with these signs to shorter time to pregnancy, independent of coital frequency. Restorative evaluation asks why cycles are irregular in women outside this model, such as those with long or absent cycles.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Attaining pregnancy is conditional upon a series of complex processes, including adequately timed intercourse, ovulation, fertilisation, and implantation. Anovulation is a first-line treatment target for couples with difficulty conceiving and is frequently examined in studies of fecundability.

Objectives

To identify whether sporadic anovulation is an important determinant of cumulative pregnancy rates and time to pregnancy among fertile women with regular menstrual cycles.

Methods

We simulated cumulative pregnancy rates and time to pregnancy for 12 consecutive menstrual cycles among 100 000 women based on data-driven probabilities of implantation, fertilisation, ovulation, and intercourse occurring in the fertile window. We assumed anovulation probabilities of 1%, 8%, or 14.5% and intercourse averaging once per week, every other day, or daily. The model incorporated reductions in implantation and fertilisation rates for successive cycles of non-pregnancy.

Results

After 12 cycles, a reduction in the per cycle incidence of anovulation from 14.5% to 1% resulted in a 4.0% higher cumulative pregnancy rate (86.7% vs 90.7%) and similar time to pregnancy (1-cycle median difference). In contrast, increasing mean unscheduled sexual intercourse frequency from weekly to every other day was associated with a 5-cycle median reduction in time to pregnancy (weekly: 7 cycles; every other day or daily: 2 cycles) and a 28.9% increase in the cumulative pregnancy rate (weekly: 59.9%, every other day: 88.8%; daily: 91.6%).

Conclusions

In presumed fertile women with regular menstrual cycles, routine investigation of anovulation may not be an informative outcome in studies of fecundability, and routine testing to ensure ovulation and treatment of anovulation are unlikely to be medically necessary. While biomarkers or cervical fluid may help time intercourse to the fertile window, time to pregnancy can also be improved through increasing the frequency of unscheduled intercourse. These findings need corroboration in large preconception time to pregnancy studies.

Topics

Menstrual Cycle Cycle Disorders Ovulatory Disturbances

Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances

Elizabeth A DeVilbiss, Joseph B Stanford, Sunni L Mumford, Lindsey A Sjaarda, Keewan Kim, Jessica R Zolton, Neil J Perkins, Enrique F Schisterman

Liz DeVilbiss, Beth DeVilbiss, Betsy DeVilbiss, E DeVilbiss, Joe Stanford, Joey Stanford, J Stanford, S Mumford, L Sjaarda, K Kim, Jess Zolton, J Zolton, N Perkins, E Schisterman

PMID 32970334 32970334 DOI 10.1111/ppe.12692 10.1111/ppe.12692 DeVilbiss et al. 2021, DeVilbiss 2021