Reproductive Endocrinology Ovulation Physiology

Systematic Review of Ovarian Activity and Potential for Embryo Formation and Loss during the Use of Hormonal Contraception

Harrison D, Buskmiller C, Chireau M, Ruppersberger LA, Yeung PP Jr

Published November 2018 The Linacre Quarterly, 85(4), 453-469
DOI 10.1177/0024363918815611 PMID 32431378 PMC PMC6322118

RRM Academy Synopsis

Hormonal Contraception May Allow Egg Release With Low Progesterone

A 2018 review of 17 studies of women on hormonal contraception reported that the most common ovarian activity recorded was a large follicle followed by low progesterone. The authors argue that follicle rupture in these cycles may mean an egg was released. They say this may add to early embryo loss. The studies measured follicles and hormones.

Key Findings

  • The review's table includes 17 studies that reported enough numbers to create a Hoogland score of 3 to 6, a system that grades ovarian activity.
  • The authors report that the most common activity was a follicle large enough to ovulate, then low luteal progesterone (Hoogland active follicle-like structure). They call it the pattern of greatest concern.
  • In a study of a vaginal ring for emergency contraception, ovulatory dysfunction occurred in 31% (15/48) of ring cycles and 6% (3/48) of control cycles (p = .003).
  • In a 1998 pill regimen study, follicular rupture occurred in 30 percent of cycles (nine of thirty). Five of those nine ruptures had decreased progesterone production.
  • The authors write that they cannot estimate ovulation rates, embryo survival rates or embryo demise rates from Hoogland scoring.

Interpretation

This is a systematic review of ultrasound and hormone studies. The review includes 17 studies of women who used hormonal contraception, each given a Hoogland score for ovarian activity. The most common finding was a large follicle, then low progesterone. The authors call this the pattern of greatest concern. They say low progesterone after a follicle ruptures may add to early embryo loss. The authors base this on other research linking progesterone to implantation. The authors note their scoring method cannot give exact rates of ovulation or embryo loss. The findings support larger studies using markers that confirm egg release.

RRM Context

Restorative reproductive medicine treats the cycle as a vital sign of health. The progesterone that follows ovulation is part of that sign too. A progesterone cutoff alone can miss a follicle that already ruptured. Suppressive medications change that pattern. Cycle charting records what happened in each cycle.

Abstract

The purpose of this review was to determine whether there is evidence that ovulation can occur in women using hormonal contraceptives and whether these drugs might inhibit implantation. We performed a systematic review of the published English-language literature from 1990 to the present which included studies on the hormonal milieu following egg release in women using any hormonal contraceptive method. High circulating estrogens and progestins in the follicular phase appear to induce dysfunctional ovulation, where follicular rupture occurs but is followed by low or absent corpus luteum production of progesterone. Hoogland scoring of ovulatory activity may inadvertently obscure the reality of ovum release by limiting the term "ovulation" to those instances where follicular rupture is followed by production of a threshold level of luteal progesterone, sufficient to sustain fertilization, implantation, and the end point of a positive β-human chorionic gonadotropin. However, follicular ruptures and egg release with subsequent low progesterone output have been documented in women using hormonal contraception. In the absence of specific ovulation and fertilization markers, follicular rupture should be considered the best marker for egg release and potential fertilization. Women using hormonal contraceptives may produce more eggs than previously described by established criteria; moreover, suboptimal luteal progesterone production may be more likely than previously acknowledged, which may contribute to embryo loss. This information should be included in informed consent for women who are considering the use of hormonal contraception.

Summary

For this study, the authors looked at English-language research articles that focused on how hormonal birth control, such as the birth control pill, may affect very early human embryos. The authors found that abnormal ovulation, or release of an egg followed by abnormal hormone levels, may often occur in women using hormonal birth control. This may increase the number of very early human embryos who are lost before a pregnancy test becomes positive. For women who are thinking about using hormonal birth control, this is important information to consider.

Topics

By this author

Related research

Reproductive Endocrinology › Ovulation Physiology › Ovulation Disorder Classification · Contraception › Oral Contraceptives › Metabolic Effects · Menstrual Cycle › Cycle Physiology › Ovulation
Donna Harrison, Cara Buskmiller, Monique Chireau, Lester A Ruppersberger, Patrick P Yeung Jr
D Harrison, C Buskmiller, M Chireau, L Ruppersberger, Pat Yeung, P Yeung
PMID 32431378 32431378 DOI 10.1177/0024363918815611 10.1177/0024363918815611 Harrison et al. 2018, Harrison 2018