الفهرس 
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Abstract
Male factor infertility accounts for 50% of all cases of infertility. Of these infertile men, 10-20% (or 1% of all men in the general population) suffer from azoospermia. Azoospermia is defined as the absence of sperm in at least two different ejaculate samples (including the centrifuged sediment). Azoospermia is clinically classified as OA (post-testicular) and NOA (pre-testicular or testicular).
Obstructive azoospermia is less common than NOA. It occurs in 15- 20% of men with azoospermia. Although NOA indicates impaired sperm production of the entire testis by definition, it has been observed that focal normal spermatogenesis can be observed in 50 to 60% of men with NOA.
Previous attempts to improve spermatogenesis in men with NOA by treatment with clomiphene, rhFSH alone, HCG alone, and clomiphene in combination with HCG and rhFSH have been successful. Although these studies have shown the benefit of some treatments, no treatments have consistently shown efficacy.
Several studies suggest that micro-TESE should become the standard in the management of men with NOA. Micro-TESE appears to improve the frequency of successful sperm retrieval in NOA patients despite the removal of dramatically less testicular tissue. Relevantly, the extraction of seminiferous tubules during micro-TESE does not compromise the subtunical blood vessels; therefore, the testicular damage is reduced as compared to a standard TESE. An improvement of sperm retrieval from a rate of 45 % with conventional TESE to a rate of 63% with micro-TESE has been reported. However, the literature reports acceptable sperm retrieval rates with different techniques including single TESE biopsy: 41.6-49.5%; multiple conventional TESE: 52.5-56 %; and micro-TESE: 35-77 %.
The objective of this study was to evaluate of the role of hormonal therapy in enhancing sperm retrieval rate in infertile men with NOA.
The study was conducted at Guys and St. Thomas Hospital, London, United Kingdom, in a period from March 2020 to March 2023. Successful sperm retrieval was comparable across all groups with basal FSH level was the most significant predictive factor for successful sperm retrieval.
Our study included a total of 315 patients, 87 received clomiphene citrate (CC group), 12 patients received CC+HCG (CC+HCG group), 11 patients received clomiphene citrate+FSH (CC+FSH group), 3 patients received clomiphene citrate
+HCG+FSH (CC+HCG+FSH group), and 202 patients were control group.
In this study, there was a statistical difference between groups according to right and left testicular size, with the control group having the largest testicular size followed by the CC+HCG+FSH group, CC group, CC+HCG group, and finally CC+FSH group. The control group had the highest basal total testosterone followed by CC+HCG+FSH group, CC group, CC+HCG group, and finally CC+FSH group, in contrast to basal FSH where the control group had the lowest value followed by CC+HCG+FSH group, CC group, CC+FSH group, and finally CC+HCG group which have the highest value (p-value=0.002). Also, the basal LH of the control group had the lowest value followed by CC group, CC+HCG+FSH group, CC+FSH group, and finally CC+HCG group which had the highest value.
In this study, the CC+HCG+FSH group had the highest post-stimulation total testosterone followed by the control group, CC group, CC+HCG group, and finally CC+FSH group (p-value=0.001), in contrast to post-stimulation estradiol where CC+FSH group had the lowest value followed by the control group, CC group but CC+HCG+FSH group and CC+HCG group could not be estimated (p-value=0.048), but post-stimulation FSH and post-stimulation LH were comparable across groups.
In this study, post-stimulation total testosterone, FSH, and LH were higher than their basal values in the CC group (p-value<0.001). Post-stimulation total testosterone was higher than its basal value in the CC+HCG group, CC+FSH group, and
CC+HCG+FSH group, however post-stimulation FSH and LH were lower than their basal values in the same groups.
There was a statistical difference between groups regarding chromosomal/ genetic abnormality; with KS was the most common abnormality.
Successful sperm retrieval was comparable across all groups in this study, where (43/87) in the CC group, (4/12) in the CC+HCG group, (4/11) in the CC+FSH group, (2/3) in the CC+HCG+FSH group, and (121/202) in the control group had successful sperm retrieval confirming the fact that even with hormonal manipulation, micro‐TESE can only “seek” spermatozoa, but not to “make” one.
In this study, SCO was the most common histopathological finding, followed by early maturation arrest. There were no significant differences between the different treatment groups regarding left and right Johnson scores.
In the current study, a total of 98 couples underwent ICSI cycles. 88 female partners underwent embryo transfer after a fresh or frozen cycle. Meanwhile, 6 cycles yielded embryos without subsequent transfer (freeze all cycles), and 4 cycles were cancelled due to poor embryo development. There was no statistical difference between groups according to number of injected oocytes, number of fertilized oocytes, number of top-quality embryos, cumulative biochemical pregnancy, cumulative clinical pregnancy, cumulative miscarriages, cumulative live birth, and number of delivered babies. There weren’t miscarriage cases in treated groups, whereas there were seven cases of miscarriage in control groups which need further studies to explain this finding.
Interestingly, men on hormone stimulation group had much better live birth rate outcomes than men with normal testosterone (control group). These findings should be approached with caution owing to the small sample size in our study, which urge the need for randomized controlled approach to hormone stimulation within a
protocol to help to delineate the effect of hormonal stimulation on the pregnancy outcome and LBR.
In current study, univariate regression analysis revealed that male age at the time of biopsy, presence of chromosomal/genetic abnormality, left testicular size, basal FSH, basal LH, post-stimulation FSH, and post-stimulation LH were significant predictors for successful sperm retrieval.
On univariate logistic regression analysis, older male at the time of biopsy was associated with slightly significantly higher successful sperm retrieval. Men without chromosomal & genetic abnormality were also more likely to have higher successful sperm retrieval, having small left testicular size was associated with significantly lower successful sperm retrieval, and low level of FSH & LH was associated with significantly higher successful sperm retrieval. Nevertheless, in multivariate analysis, basal FSH was the only significant predictor for successful sperm retrieval where high level of basal FSH was associated with lower odds of sperm retrieval.
Recommendations
After six months of hormonal therapy and/or the patient has reached the target blood testosterone levels, we advise micro-TESE if the patient is still azoospermic in the periodic semen study.
Despite their promise, findings of the trials that are now available are not adequate to advise hormone therapy for every patient with NOA prior to SRT. Thus, according to the latest AUA/ASRM guidelines regarding the diagnosis and treatment of male infertility, patients with NOA should be made aware of the little evidence supporting hormonal manipulation therapy before undergoing SSR.
There is an urgent need for multicentre randomized controlled approaches to assess the role of hormone stimulation on pregnancy outcomes in NOA patients.