Abstract

Abstract Study question Does the sperm retrieved surgically by MD-TESE of men with Non-Obstructive Azoospermia affect the live birth sex ratio? Summary answer Our data indicates that sperm retrieved in men with non-obstructive azoospermia alters the sex ratio in favor of female offspring. What is known already Non-Obstructive Azoospermia is the most severe form of male infertility and is the most common cause of Azoospermia. Among the different surgical techniques, MD-TESE gives the highest rate of sperm retrieval and when combined with intracytoplasmic sperm injection (ICSI), live births had been achieved with variable success, Sex ratio of offspring can vary substantially due to several variables, however no studies have investigated the resultant birth sex ratio in this setting. Study design, size, duration Retrospective Cohort study. Data were collected between May 2009 and December 2019. A total of 100 consecutive men with non-obstructive Azoospermia underwent MD-TESE for sperm retrieval. 46 couples underwent ICSI and live birth rate, cumulative live birth rate and sex ratio of offspring analysed. Participants/materials, setting, methods One-hundred men underwent MD-TESE out of which 46 proceeded with ICSI. Demographic data including male and female age, testicular volumes and serum hormone values are given as mean ± SD with a range (minimum and maximum). Fertility outcomes including sperm retrieval, fertilization rate, number of embryos transferred, and live birth rates and cumulative live birth rates were recorded. Chi-square test was performed to compare the proportions. Main results and the role of chance Sperm retrieval was successful in 58%(58/100). Testicular volume and hormonal parameters did not vary among patients with positive or negative sperm retrieval. Histology gave best correlation with sperm retrieval. Hypospermatogenesis yielded the highest sperm retrieval 93%(26/29), followed by Maturation arrest 78%(7/9), then Hyalinosis 46% (6/13) and lastly Sertoli cell only 38%(19/50). 46 couples underwent ICSI cycles where the mean age of patients and their wives were 36.4 ± 3.7y and 33.0 ± 4.3y. Fertilization rate and mean number of transferred embryos were 51.4 % and 1.7. Live birth rate and Cumulative Live Birth rate per Embryo transfer were 60.5% (26/43) and 74.4% (32/43) and per started ICSI cycle were 56.5% (26/46) and 69.6% (32/46), with a twin rate of 15.3%(4/26). Mean gestational length and mean body weight at birth were 39.0 ± 1.4w and 3228.5 ± 5.5 g. Number of live offspring were 36 (Female: Male = 26:10) giving rise to sex ratio of 2.6 to1 in favor of female offspring (P < 0.05). There were no neonatal death, and one baby had phenylketonuria. Limitations, reasons for caution This is the first study to test the hypothesis of sex ratio variation related to the source of sperm; the strength of our study is that all procedures were performed by the same surgeon, so there are no operator-dependent differences. This finding needs to be confirmed in larger cohort studies. Wider implications of the findings It has been demonstrated that different stressors may alter the sex of the offspring. While in the present study the stressor is the parental hypogonadism associated with non-obstructive azoospermia, We hypothesise that testicular environment may direct spermatogenesis in favor of X carrying sperm around the time of sperm retrieval. Trial registration number N/A

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