Reduced Testicular Steroidogenesis and Increased Semen Oxidative Stress in Male Partners as Novel Markers of Recurrent Miscarriage

Author:

Jayasena Channa N123,Radia Utsav K1,Figueiredo Monica12,Revill Larissa Franklin3,Dimakopoulou Anastasia12,Osagie Maria3,Vessey Wayne2,Regan Lesley3,Rai Rajendra3,Dhillo Waljit S1

Affiliation:

1. Section of Investigative Medicine, Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK

2. Department of Andrology, Hammersmith Hospital, London, UK

3. Department of Obstetrics & Gynecology, St. Mary's Hospital, London, UK

Abstract

Abstract BACKGROUND Recurrent pregnancy loss, (RPL) affecting 1%–2% of couples, is defined as ≥3 consecutive pregnancy losses before 20-week' gestation. Women with RPL are routinely screened for etiological factors, but routine screening of male partners is not currently recommended. Recently it has been suggested that sperm quality is reduced in male partners of women with RPL, but the reasons underlying this lower quality are unclear. We hypothesized that these men may have underlying impairments of reproductive endocrine and metabolic function that cause reductions in sperm quality. METHODS After ethical approval, reproductive parameters were compared between healthy controls and male partners of women with RPL. Semen reactive oxygen species (ROS) were measured with a validated inhouse chemiluminescent assay. DNA fragmentation was measured with the validated Halosperm method. RESULTS Total sperm motility, progressive sperm motility, and normal morphology were all reduced in the RPL group vs controls. Mean ±SE morning serum testosterone (nmol/L) was 15% lower in RPL than in controls (controls, 19.0 ± 1.0; RPL, 16.0 ± 0.8; P < 0.05). Mean ±SE serum estradiol (pmol/L) was 16% lower in RPL than in controls (controls, 103.1 ± 5.7; RPL, 86.5 ± 3.4; P < 0.01). Serum luteinizing hormone and follicle-stimulating hormone were similar between groups. Mean ±SE ROS (RLU/sec/106 sperm) were 4-fold higher in RPL than in controls (controls, 2.0 ± 0.6; RPL, 9.1 ± 4.1; P < 0.01). Mean ±SE sperm DNA fragmentation (%) was 2-fold higher in RPL than in controls (controls, 7.3 ± 1.0; RPL, 16.4 ± 1.5; P < 0.0001). CONCLUSIONS Our data suggest that male partners of women with RPL have impaired reproductive endocrine function, increased levels of semen ROS, and sperm DNA fragmentation. Routine reproductive assessment of the male partners may be beneficial in RPL.

Funder

Section of Investigative Medicine

NIHR Imperial Biomedical Research Centre Funding Scheme

NIHR Post-Doctoral Fellowship

SRF Vacation Grant

Imperial College Healthcare Charity

Canadian Imperial Bank of Commerce

Publisher

Oxford University Press (OUP)

Subject

Biochemistry, medical,Clinical Biochemistry

Reference38 articles.

1. Recurrent miscarriage;Stirrat;Lancet,1990

2. Frequency of factors associated with habitual abortion in 197 couples;Stephenson;Fertil Steril,1996

3. Anatomic factors in recurrent pregnancy loss;Devi Wold;Semin Reprod Med,2006

4. Infectious causes of recurrent pregnancy loss;Byrn;Clin Obstet Gynecol,1986

5. Royal College Obstetricians and Gynaecologists (RCOG). The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. R Coll Obstet Gynaecol2011;17:1–18. https://www.rcog.org.uk/globalassets/documents/guidelines/gtg_17.pdf (Accessed September 2018).

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