Interaction between serum levels of Anti-Mullerian Hormone and the degree of sperm DNA fragmentation measured by sperm chromatin structure assay can be a predictor for the outcome of standard in vitro fertilization.

Peter Zarén,Emir Henic,Sara Alson,Aleksander Giwercman,Mona Bungum,Joël R Drevet

doi:10.1371/journal.pone.0220909

Peter Zarén, Emir Henic + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0220909

Copy DOI

Journal: PloS one	Publication Date: Aug 8, 2019
Citations: 3	License type: CC BY 4.0

Affiliation: Skåne University Hospital, Lund University

Abstract

Serum levels of Anti-Mullerian Hormone (AMH) have been shown to be biomarker for prediction of the quantitative aspects of ovarian reserve. On the male side, sperm chromatin structure assay (SCSA) DNA fragmentation index (DFI) has been demonstrated to be an important predictor of outcomes in standard IVF procedures but to less degree in intracytoplasmic sperm injection procedures (ICSI). The purpose of this study was to investigate whether the combination of female AMH serum levels and sperm DFI adds to prediction of the outcome of assisted reproduction. A total of 352 couples was included (ICSI-148: IVF-204) A venous blood sample was drawn for AMH analysis before IVF/ICSI treatment. DFI was measured in the ejaculate used for assisted reproduction. Regression models for the following odds ratio calculations were constructed: for obtaining at least one Good Quality Embryo; for live birth in all procedures; for pregnancy in procedures where embryo transfer was performed; for miscarriage. For DFI increase by 10 percentage points (not increased DFI as reference) odds ratio for Good Quality Embryo was statistically significantly lower when AMH was at lower quartile (AMH <12 pmol/L; OR = 0.29, 95% CI: 0.14–0.59,) but not when AMH was at upper quartile (AMH ≥ 36 pmol/L; OR = 0.95, 95% CI: 0.43–2.13,). The marginal effect of an increase in DFI by 10 percentage points was statistically significant only when AMH < 25.2 pmol/L. Similar results were obtained as considers live birth following standard IVF. No interactions were seen for standard IVF in relation to the risk of miscarriage and for any of the outcomes when ICSI was used as method of treatment. We conclude that the impact of high DFI on the outcome of standard IVF is most pronounced if the female partner has relatively low AMH levels. This finding may help in defining the role of sperm DNA integrity testing in management of infertile couples. It may also explain some of the heterogeneity in results of studies focusing on predictive value of DFI measurements in assisted reproduction.

Highlights

In vitro fertilization (IVF) is a clinically established practice for couples experiencing infertility, annually contributing to over 100 000 infants born in Europe and 50 000 in the United States [1, 2]
Odds ratios (OR) for Good Quality Embryos (GQE) when DNA fragmentation index (DFI) increased by 10 percentage points vs not increased was statistically significantly lower when Anti-Mullerian Hormone (AMH) was at lower quartile (AMH < 12 pmol/L; OR = 0.30, 95% CI: 0.14– 0.62,) but not when AMH was at upper quartile (AMH 36 pmol/L; OR = 0.91, 95% CI: 0.40– 2.04,)
The oocyte yield-adjusted OR for live birth for DFI increased by 10 percentage points vs not increased was statistically significantly lower when AMH was at lower quartile (AMH < 12 pmol/L; OR = 0.42, 95% CI: 0.20–0.88) but not when AMH was at upper quartile (AMH 36 pmol/L; OR = 0.57, 95% CI: 0.28–1.18,)

Summary

Introduction

In vitro fertilization (IVF) is a clinically established practice for couples experiencing infertility, annually contributing to over 100 000 infants born in Europe and 50 000 in the United States [1, 2]. Success rates have remained low during recent years, on average, with less than a third of cycles resulting in live birth. Given the cost and the emotional distress of the procedure itself [3], a better understanding of factors predicting IVF outcomes is warranted. Its ability to predict outcomes in IVF procedures has so far been limited, with recent meta-analyses showing only weak associations between AMH levels and pregnancy and live birth rates, respectively [8, 9]. Factors related to male reproductive function are assumed to play a role in as many as 50% of infertility cases [10]. From a clinical point of view, it is, plausible to take both markers of female and male fertility into account when predicting the outcome of applying assisted reproduction techniques (ART)

Objectives

Methods

Results

Conclusion