# Male Stress Is Associated with Ovarian and Endometrial Responses in ICSI Cycles: Is Seminal Plasma the Linchpin?

## TL;DR

Male stress may affect female fertility outcomes in ICSI cycles by altering the composition of seminal plasma.

## Contribution

This study identifies distinct male stress phenotypes and their impact on female fertility outcomes during ICSI.

## Key findings

- Women with partners showing chronic stress (phenotype-2) had lower oocyte counts and pregnancy rates.
- Seminal plasma from stressed males may have a dual role in fertility depending on stress type.
- Endometrial thickness and fertilization rates were reduced in women with phenotype-2 partners.

## Abstract

Evidence indicates that seminal plasma (SP) has pregnancy-favorable biological effects, but there is no definitive proof that exposure to SP increases pregnancy rates in assisted reproductive techniques. We previously showed that this discrepancy may be due to male stress altering SP composition. This study investigated the association between male stress biomarkers in saliva, serum and SP and key determinants of female fertility in women exposed to their partner’s SP during the intracytoplasmic sperm injection (ICSI) cycle. The prospective pilot study included couples with tubal infertility who had unprotected intercourse during the ICSI cycle, supplemented by intravaginal SP injection on the oocyte retrieval day. Salivary cortisol and seminal noradrenaline were quantified by enzyme-linked immunosorbent assay to assess the activity of the hypothalamic–pituitary–adrenal axis and sympathetic nervous systems. Seminal interleukin-18 was measured using LegendPlex™ technology. Cluster analysis of male stress biomarkers identified two neuroendocrine-immune (NEI) phenotypes, characterized by signs of acute (phenotype-1) and chronic (phenotype-2) stress. Women with NEI phenotype-2 partners had fewer collected, mature, and fertilized oocytes, thinner endometrium, and significantly lower pregnancy rates (18.2%) compared to those with NEI phenotype-1 partners (84.6%). These data may suggest a dual role for SP in female fertility, depending on the type of male stress.