Abstract Study question Assess the effectiveness of treatments at a Male Endocrine Fertility Clinic, over a five-year period, through spermatogenesis rates and fertility outcomes via a patient-centred questionnaire Summary answer Rate of successful spermatogenesis was 68% and live birth (LB) 36%. Trend towards lower odds ratio for LB was noted, if partners reported subfertility. What is known already Approximately half of infertility cases are due to male factor, with up to 70% being idiopathic. The remaining 30% of male factor infertility is attributed to primary testicular or central endocrine disorders. Identifying the aetiology of male hypogonadism is important to determine treatment strategies, such as gonadotrophin therapy and surgical testicular sperm extraction (TESE). Although treatment pathways for hypogonadal men with infertility have been established over the last thirty years, the effectiveness of such pathways is diverse and data from large studies are scanty. Study design, size, duration A questionnaire, covering basic demographic data about both partners, as well as health conditions affecting fertility, was prospectively sent out to 168 men who had received gonadotrophins for induction of spermatogenesis between 2017 and 2021. Men presented with azoospemia or severe oligospermia (<5million/ml). Eighty-four questionnaires (50%) were completed. Medical records were reviewed, to validate participant responses, identify baseline endocrine biochemistry from the start of spermatogenesis and seminal parameters at the end of the process. Participants/materials, setting, methods Mean age of participants was 38 years (range 21-63). Twenty-two men had primary (26%) and the remaining 74% central hypogonadism. The questionnaire was sent via email and responses were anonymised with each participant given a unique study identification number. All statistical analysis was performed using Graph Pad Prism. All hypothesis testing was two-tailed; p < 0.05 was considered statistically significant. Main results and the role of chance 58% of men (49/84) had sperm seen in their ejaculate and 10% of men (8/84) after microTESE. Men with persistent azoospermia were more likely to have a diagnosis of primary hypogonadism (PH) and small testicular size. 28% (13/47) had partners, who conceived spontaneously and delivered healthy babies. 9% (4/47) had a live birth after ART. Only 1 of 2 men with PH seeking fertility, had a partner with a positive pregnancy test, which resulted in a miscarriage. Age, body mass index, alcohol intake, baseline LH, FSH and testosterone were not significantly different between men with or without a live birth. Men without a live birth trended towards having partners with subfertility (pelvic inflammatory disease, endometriosis or polycystic ovarian syndrome), though this did not reach statistically significance (Odds ratio 6.9, 95%CI: 0.8 – 59.9, p = 0.07). Also, LBR was lower for female partners above 35 years, compared to LBR for younger female partners; 35% (6/17) for couples with partners above 35 years, versus 65% (11/17) for couples with partners below 35 years. Seminal parameters were not statistically different between men with or without live births, which supports the possibility that factors other than male reproductive status affected fertility outcomes. Limitations, reasons for caution The 50% response rate to our questionnaire-based study means outcomes may not be representative of all patients attending our clinic and can introduce bias with differences between responders and non-responders. Furthermore, the questionnaire used was not externally validated and its data may not be representative of outcomes in other centers. Wider implications of the findings Our study highlighted successful spermatogenesis and comparable live birth rates to other male fertility services worldwide. It is the first to compare the clinical, biochemical and seminal characteristics between men with live births versus those without a live birth. Ensuring couples are well informed is essential to further successful outcomes. Trial registration number not applicable
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