Preimplantation loss of fertilized human ova: estimating the unobservable

Allen J Wilcox; Quaker Harmon; Kevin Doody; Don P Wolf; Eli Y Adashi

doi:10.1093/humrep/deaa048

Research Methods Evidence Synthesis

Preimplantation loss of fertilized human ova: estimating the unobservable

Wilcox AJ, Harmon Q, Doody K, Wolf DP, Adashi EY

Published April 28, 2020 Human reproduction (Oxford, England), 35(4), 743-750

DOI 10.1093/humrep/deaa048 PMID 32296829 PMC PMC8287936

RRM Academy Synopsis

Modeling estimates 40 to 50% of fertilized human eggs fail to implant

A 2020 modeling study estimates that 40 to 50% of fertilized human eggs are lost before they implant among couples in their prime years. The authors combined published data on pregnancy chances, sterility, missed ovulation and timing of sex.

Key Findings

The model assumes implantation in 36% of first-cycle attempts and a live birth in 24% of couples in that cycle.
The model assumes sterility (2%), missed ovulation (4%) and mistimed intercourse (8%), so fertilization is impossible in an average of 14% of cycles, leaving 86 of 100 cycles.
Assuming 64 to 90% of eggs are fertilized in the presence of sperm, preimplantation loss ranges from 35 to 53%. Varying every other assumption leaves a range of 40 to 50%.
Combined with recognized losses, 60 to 67% of conceptions are lost in total, and 33 to 40% of all conceptuses survive to live birth.
The authors' calculations suggest a live birth in 25 to 31% of eggs fertilized in vitro, against 33% to 40% of eggs fertilized in the body.

Interpretation

The study is a modeling analysis. The authors built the estimate from published figures and data from one IVF clinic, because fertilization in the body cannot be observed. They used human IVF data for the low end of the fertilization range and animal data for a conjectural high end. The authors name the fertilization rate as the main uncertainty. They say their IVF comparison, built on indirect calculations, gives no clear indication of where IVF might be improved.

RRM Context

The model counts missed ovulation (4%) and mistimed intercourse (8%) among the reasons a cycle cannot produce a fertilized egg. Cycle charting and ovulation evaluation bring both into view, and both are central to restorative reproductive medicine. The authors' estimates suggest eggs fertilized in vitro may be moderately less likely to reach a live birth. The model puts them below eggs fertilized in the body. That fits an approach that works with the body's own cycle.

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

Abstract

Study Question

What proportion of fertilized human ova are lost before implantation?

Summary Answer

An estimated 40 to 50% of fertilized ova fail to implant.

What Is Known Already

Preimplantation loss is not detectable with current technology. Published estimates of preimplantation loss range from 10 to 70%.

Study Design, Size, Duration

We combine data from epidemiologic, demographic, laboratory and in vitro fertilization studies to construct an empirical framework for the estimation of preimplantation loss. This framework is summarized in a user-friendly Excel file included in supplement.

Participants/Materials, Setting, Methods

We draw from multiple sources to generate plausible estimates of fecundability, sterility, transient anovulation, intercourse patterns and the proportion of ova fertilized in the presence of sperm. We combine these estimates to generate a summary estimate of preimplantation loss. This estimate can be considered an average for couples in their prime reproductive years.

Main Results and the Role of Chance

Under a plausible range of assumptions, we estimate that 40 to 50% of fertilized ova fail to implant.

Limitations, Reasons for Caution

A crucial factor in estimating preimplantation loss is the probability that an ovum will be fertilized when exposed to sperm. Human data are available only from in vitro fertilization (IVF), which may not accurately represent events in vivo. We therefore assume a range of in vivo fertilization rates, from 64% (human IVF data) to 90% (mouse data).

Wider Implications of the Findings

Our estimate of preimplantation loss takes into account the biological processes relevant to fertilization and loss. Using this empirical basis for estimation, we find support for the usual assumption that risk of loss is highest in the earliest days following fertilization. Furthermore, this framework can provide improved estimates as better reproductive data become available. To the extent that our estimates are accurate, more fertilized ova are apparently lost in vitro than in vivo, suggesting that further improvements in IVF success rates may be possible.

Study Funding/Competing Interests

This study was supported by the Intramural Program of the National Institute of Environmental Health Sciences, NIH. Professor Adashi serves as Co-Chair of the Safety Advisory Board of Ohana Biosciences, Inc. The other authors have no competing interests.

Trial Registration

N/A.

Topics

Research Methods

Evidence Synthesis Meta-Analysis

Research Methods › Evidence Synthesis › Meta-Analysis

Allen J Wilcox, Quaker Harmon, Kevin Doody, Don P Wolf, Eli Y Adashi

A Wilcox, Q Harmon, K Doody, Donald Wolf, D Wolf, E Adashi

PMID 32296829 32296829 DOI 10.1093/humrep/deaa048 10.1093/humrep/deaa048 Wilcox et al. 2020, Wilcox 2020

Keywords

epidemiology, fertilization, implantation, oocyte quality, pregnancy

Preimplantation loss of fertilized human ova: estimating the unobservable

Modeling estimates 40 to 50% of fertilized human eggs fail to implant

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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