Chromosomal Analysis and Health Status of Children Conceived to Men During or Following Dibromochloropropane-Induced Spermatogenic Suppression

Although the mutagenic effect of Dibromochloropropane (DBCP) on experimental mammal systems has been described, its possible effect on the human genome has not yet been investigated. The present study describes the results of chromosomal analysis and health evaluation of offspring conceived to families during and after paternal exposure to DBCP. Ten children conceived during or following severe exposure and four who were conceived prior to DBCP exposure were evaluated. The chromosomal constitution of peripheral lymphocytes was normal in all cases. The mode of delivery, birth weight, physical examination and growth pattern were normal. No congenital malformations were detected. One spontaneous abortion out of 23 pregnancies was recorded. These results suggest that paternal exposure to DBCP, severe enough to cause azoospermia or oligozoospermia did not alter the paternal sperm genome or the chromosomal constitution of offspring conceived during or after exposure. This is further supported by the excellent health and lack of malformations among the children, along with the low rate of spontaneous abortions in the families studied.     

Dibromochloropropane-induced Reduction of the Sex-ratio in Man

The present study evaluated the effect of paternal exposure to Dibromochloropropane (DBCP) during its production, on the sex ratio of offsprings conceived during the exposure period. The study population consisted of 30 families of which 13 fathers became azoospermic, 8 oligozoospermic and 9 normozoospermic. Of the 89 pregnancies recorded, 68 culminated in the birth of live infants. The prevalence of male infants conceived during the pre-exposure period was 52.9% , in contrast to 35.2% for boys conceived during exposure. For the combined azoospermic and oligozoospermic groups, a significantly low prevalence of male infants of 16.6% (p less than 0.025) was found. It is concluded that paternal exposure to DBCP during its production process is associated with a significant decrease in the sex ratio of offsprings conceived during the exposure period. This drop in the sex ratio might be a reflection of the early effect of DBCP on male reproductive performance before a state of severe testicular dysfunction and infertility is reached.     

The paternal genome and the health of the assisted reproductive technology child

As a number of children born by assisted reproductive technology (ART) are increasing each year across the developed world, the health of such offspring is a matter of public concern. Does the integrity of the paternal genome impact on offspring health? In societal terms, as birth rates fall, and the Western population become unsustainable, do the benefits outweigh the costs of creating and providing for this ART conceived subpopulation? There are little data to date to answer these questions. The long-term health of such children has largely been ignored, and success measured only by early (prebirth) outcomes such as embryo quality or pregnancy. However, there are powerful paradigms such as ageing and smoking that give vital clues as to the potential impact of unhealthy spermatozoa on disease risk, mental and physical health, fertility and mortality of these offspring.     

Short‐term safety evaluation of the offspring conceived by 7272 artificial insemination cycles with donor spermatozoon

This case–control study was designed to investigate the safety of the AID technology. The health status of the offspring conceived by 1620 couples who underwent 7272 AID cycles in our Center for Reproductive Medicine between June 2006 and December 2012 was retrospectively analysed. The control group included 1018 women who naturally conceived and delivered in the same period. Twin birth rate was significantly higher in the AID group (no triplet birth) than in the control group (2.01% versus 0.39%, P < 0.01). In the AID group, Caesarean delivery was used in 1299 cases (81.65%), spontaneous vaginal delivery (18.04%) and forceps‐assisted vaginal delivery (0.31%).There was no significant difference in male/female ratio of the offspring between AID and control groups (113.55 : 100 versus 113.36 : 100, P > 0.05). Compared to natural pregnancy, a pregnancy through AID resulted in higher multiple birth rate, premature delivery rate and neonatal congenital malformation rate. Increased multiple birth rate was attributable to ovulation induction, and increased rate of low‐birthweight infants was related to multiplets and premature delivery. Caesarean delivery was preferred in couples who received AID treatment. The male/female ratio of the AID offspring was similar between natural pregnancy and AID pregnancy.     

供精精液行辅助生殖技术出生子代安全性评估

目的:本研究调查应用供精者精液实施辅助生殖技术(ART),包括供精人工授精(AID)、供精体外受精(IVF-D、ICSI-D)与应用丈夫精液经ART(AIH、IVF、ICSI)出生子代缺陷的发生率,从而评价应用供精者精子实施ART出生子代的安全性。方法:2005年1月至2009年10月,上海市人类精子库向全国11家医疗机构供精,实施供精ART出生子代904例。对照组为4家生殖医学中心,同期对不育夫妇实施丈夫精液ART出生子代4 195例。统计两类精液实施ART出生子代的数量与出生缺陷的例数及病种分类,比较两种精液来源获得子代出生缺陷的发生率。结果:应用供精者精液实施ART获得子代出生缺陷7例(0.77%),使用丈夫精液出生缺陷42例(1.00%),其差异无显著性(P>0.05)。结论:应用供精者精子实施ART出生子代同夫精ICSI出生的子代相比,出生缺陷的种类没有明显差异,但前者的出生缺陷率明显低于后者,就目前结果而言,供精辅助生殖技术更具安全性。     

Iodine 131 thyroid ablation in female children and adolescents: Long-term risk of infertility and birth defects

Background: The use of radioactive iodine, or iodine 131 (¹³¹I), for remnant thyroid ablation and the treatment of cervical and distant metastatic disease in patients with thyroid cancer is well accepted.¹³¹I concentrates in the bladder, and irradiation to the ovaries has been theorized to increase the risk of infertility and birth defects in subsequent offspring. Methods: We conducted a retrospective review of the charts of 154 children and adolescents treated at our institution for thyroid cancer between 1951 and 1991. Review of these charts identified 68 females diagnosed with thyroid cancer, ≤20 years of age, who received¹³¹I as part of their therapy at our institution. Charts were reviewed and patients recontacted, and initial tumor, date of diagnosis, and¹³¹I administration, including doses, were recorded. Complete pregnancy histories including current health status of the children were also recorded. Results: Twenty-two patients who never attempted pregnancy were excluded from analysis. Eleven patients could not be contacted and were considered lost to follow-up and thus excluded from the study. In the remaining 35 patients, mean age at¹³¹I administration was 18.3 years (range 14.1–20.8), mean followup, 16.8 years (range 5.6–39.8), and mean¹³¹I dose, 148.53 mCi (range 77.2–250). Three patients were diagnosed infertile after extensive workup (8.6%). The remaining 32 patients had 69 pregnancies resulting in 60 term and four premature deliveries. There were two elective abortions for nonmedical reasons and three spontaneous abortions. Only two children were conceived within 1 year of¹³¹I therapy. Both were born with birth defects that proved fatal within 8 months. No other children were born with birth defects. One other child born with an estimated gestational age of 27 weeks died due to complications related to his prematurity. No anomalies were noted at autopsy. Of the 61 children alive for follow-up, no major health problems were identified other than asthma in two children. Conclusions: ¹³¹I, used in doses up to 250 mCi, is not associated with any long-term risk of infertility. The risks of infertility or birth defects are not different from those of the general population. Because the two children with birth defects were born to mothers treated either during pregnancy or 6 months before conception, it might be wise to suggest avoiding pregnancy for up to 1 year after¹³¹I treatment. Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

The effects of Y chromosome microdeletions on in vitro fertilization outcomes,health abnormalities in offspring and recurrent pregnancy loss

Male factor infertility accounts for approximately 50% of all infertility evaluations. A common cause of severe oligozoospermia and azoospermia is Y chromosome microdeletions (YCMs). Men with these genetic microdeletions must typically undergo assisted reproductive technology (ART) procedures to obtain paternity. In this review, we performed a thorough and extensive search of the literature to summarize the effects of YCMs on in vitro fertilization (IVF) outcomes, health abnormalities in offspring and recurrent pregnancy loss (RPL). The PubMed database was searched using specific search terms and papers were identified using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Sperm retrieval amongst men with complete AZFa and/or AZFb deletions is extremely rare and thus data on ARTs is largely unavailable. In AZFc-deleted men undergoing assisted reproduction, the collective fertilization rate (FR) is 59.8%, the clinical pregnancy rate is 28.6% and the live birth rate is 23.4%. When successful, the YCM is always transmitted to the male offspring and the deletion size either remains unchanged or widens. YCMs generally result in decreased fertilization, clinical pregnancy and live birth rates compared to men with intact Y chromosomes during ART interventions. There is a minimal or absent association of YCMs with abnormalities in the offspring or RPL.     

Fertility outcome of patients with testicular tumor： before and after treatment

Testicular cancer （TC） is the most curable type of cancer, with a survival rate of more than 95%. Oncologists are faced with the challenge that gonadotoxic cancer treatments can compromise future fertility, either temporarily or permanently. Our aim was to investigate the long-term effects of TC treatments on male fertility and on the offspring of patients who had received these treatments. Between January 1996 and December 2010, 125 eligible patients, ranging from 18 to 54 years （median age 36.3 _＋ 15.7）, with unilateral TC underwent surgery, chemotherapy or radiotherapy at our center. Some of these patients had their semen samples cryopreserved in the Shanghai Human Sperm Bank. The clinical data were evaluated, and questionnaire and telephone follow-up surveys were given to all patients. The data were analyzed to determine the patients＇ fertility status pre- and posttreatment. Of the 125 eligible patients, 93.6% （117/125） were accessible and were evaluated. Among 81 men who were married before diagnosis, 21 had conceived successfully before diagnosis and six reported azoospermia. Posttreatment conception was attempted by 73 men; of these, 16 conceived naturally and 19 conceived by artificial reproductive techniques, resulting in 37 healthy babies with no congenital malformations. Of the patients who had not conceived before treatment, 21.9% （21/96） banked their sperm and 23.8% of these patients （5/21） subsequently used the banked sperm. Retroperitoneal lymph node dissection, chemotherapy and radiotherapy were the most highly correlated with lack of conception to TC patients with the desire for biological conception. There is no birth defects or childhood malignancies. post-TC treatment. Sperm banking should be recommended evidence to suggest that TC treatments are associated with     

Ionising radiation: are orthopaedic surgeons' offspring at risk?

The hazards of exposure to ionising radiation are well documented. Fears have been raised that occupational exposure to ionising radiation by orthopaedic surgeons may have detrimental effects on the future health of their unborn offspring. The current members of the British Orthopaedic Trainees' Association and orthopaedic consultants appointed during the last 5 years in the United Kingdom were contacted using a postal questionnaire. Obstetricians and gynaecologists of a similar age group were also contacted to act as the control group. The collected data were compared with the latest national data as published by the Office of Population Censuses and Surveys for England and Wales (OPCS, 1991). In all, 504 questionnaires were posted to orthopaedic surgeons and 1597 to obstetricians and gynaecologists. Reply rates were 334 (66%) and 986 (62%), respectively. Our data reveal a higher rate of congenital abnormalities as compared with the normal population in both groups (P < 0.001). However, there were no statistically significant differences in the rate of congenital abnormalities between the offspring of orthopaedic surgeons and obstetricians and gynaecologists (P = 0.78). These findings suggest that the increased rate of congenital abnormalities observed in both groups is more likely to be associated with factors other than exposure to X-rays. In this study, male surgeons had a higher incidence of female children compared with the normal population (P = 0.01). The incidence of childhood malignancies does not appear to be raised in either group. These findings suggest that the current levels of occupational exposure to X-rays by orthopaedic surgeons is unlikely to be associated with an increased risk of congenital abnormalities or childhood malignancies in their children.     

Transmission of maternal islet antibodies and risk of autoimmune diabetes in offspring of mothers with type 1 diabetes

It is suggested that the maternal transmission of islet autoantibodies increases the risk of autoimmune diabetes in mice. The aim of this study was to determine whether fetal exposure to islet autoantibodies modified the risk of type 1 diabetes in humans. Islet autoantibodies were measured at birth in 720 offspring of mothers with type 1 diabetes. Offspring were prospectively followed for the development of multiple islet autoantibodies and diabetes. Offspring who were GAD or IA-2 autoantibody positive at birth (n = 678) had significantly lower risks for developing multiple islet autoantibodies (5-year risk 1.3%) and diabetes (8-year risk 1.1%) than offspring who were islet autoantibody negative at birth (5.3%, P = 0.008; and 3%, P = 0.04, respectively). Risk remained reduced after adjustment for birth weight, gestational age, or maternal diabetes duration (adjusted hazards ratio 0.25, P = 0.007 for multiple islet autoantibodies; 0.25, P = 0.04 for diabetes). Protection in offspring with islet autoantibodies at birth was most striking in offspring without the HLA DRB1*03/DRB1*04-DQB1*0302 genotype. Maternal transmission of antibodies to exogenous insulin did not affect diabetes risk in offspring. These findings suggest that fetal exposure to islet autoantibodies in children born to mothers with type 1 diabetes may be protective against future islet autoimmunity and diabetes.     

Higher offspring birth weight predicts the metabolic syndrome in mothers but not fathers 8 years after delivery: the Pune Children's Study

In Europid populations, low birth weight of offspring predicts insulin resistance in the mother and cardiovascular disease in both parents. We investigated the association between birth weight of offspring and obesity and cardiovascular risk in the parents of 477 8-year-old children born at the King Edward Memorial Hospital, Pune, India. Eight years after the birth of the child, mothers (33 years of age, n = 459) of heavier babies were taller and more obese (BMI, fat mass, and waist circumference, all P < 0.001) than mothers of lighter babies. Increasing offspring birth weight predicted higher homeostasis model assessment for insulin resistance (P < 0.01) and metabolic syndrome in mothers (P < 0.001) (adjusted for offspring sex and birth order, maternal age, and socioeconomic status) but not hyperglycemia. Fathers (39 years of age, n = 398) of heavier babies were taller and heavier, independent of maternal size (P < 0.01, both), but were not more insulin resistant. Unlike other reports, lower offspring birth weight did not predict insulin resistance in fathers. Thus, urban Indian parents have a higher risk of being obese 8 years after delivery of a heavier child. Mothers but not fathers of heavier babies also have a higher risk of being insulin resistant and developing the metabolic syndrome. Our findings highlight the need for a better understanding of the relation between fetal growth and future health before contemplating public health interventions to improve fetal growth.     

女性肾移植受者妊娠结果及子代健康状况随访

目的 评价女性肾移植受者妊娠结果及子代健康状况的长期随访结果. 方法 回顾性分析1978年4月至2011年4月妊娠＞5个月的15例肾移植受者资料,并对其子代进行随访.妊娠时年龄(28.5±5.7)岁,妊娠距移植时间(53.4±19.7)个月.产后随访(11.5±6.9)年. 结果 15例受者采用以环孢素或他克莫司为主的免疫抑制剂方案.12例母、子女身体状况及移植肾功能正常;1例产下一男婴2周后因并发肺部感染、心力衰竭,带正常功能移植肾死亡;2例分别于妊娠第21、23周发生移植肾慢性排斥反应,终止妊娠,经治疗无效后摘除移植肾.13例胎儿均经剖宫产娩出后存活,胎龄(35.2±4.0)周,出生体质量(2510 ±68)g,Apgar评分均为10分.13例婴儿出生时无生理缺陷,体格发育无异,出生后以人工喂养.13例儿童智力、体格以及心理发育与同龄者无异常,7例0～2岁时发生反复呼吸道感染,1例诊断为注意力缺陷多动障碍.目前子代年龄3 ～21岁. 结论 严格妊娠指征,肾移植女性受者在术后3年后能够成功妊娠、分娩,长期随访显示患者子代健康状况良好.     

Type 2 diabetes and low birth weight: the role of paternal inheritance in the association of low birth weight and diabetes

Lower birth weight is associated with an increased occurrence of type 2 diabetes in later life. Whether this relationship is explained by environmental or genetic factors is unknown. We have examined the potential for genetic influences by determining whether parental diabetes is associated with lower birth weight in 1,608 children of known birth weight and gestational age born between 1941 and 1993 in the Gila River Indian Community in Arizona. The previously described relationships of maternal diabetes to increased birth weight and offspring diabetes were observed. In contrast to this we have determined novel relationships between low birth weight and paternal diabetes. The offspring of diabetic fathers were, on average, 78 g lighter than the offspring of nondiabetic fathers. For fathers, lower birth weight in their offspring was associated with an increased risk of later diabetes, i.e., fathers of offspring in the lowest quintile of birth weight, who were not diabetic at the time of birth of their child, had a 1.8-fold increased risk of developing diabetes later in life (95% CI 1.2-2.7; P = 0.004). For children, lower birth weight predicted diabetes in the offspring if paternal but not maternal diabetes was present, but it was not associated with higher plasma glucose if neither parent had diabetes. We conclude that the risk of diabetes associated with low birth weight is strongly related to the development of paternal diabetes, suggesting a genetic link between lower birth weight and later diabetes.     

Congenital anomalies in the offspring of rats after exposure of the testis to an electrostatic field

The effect of electrostatic field treatment of the testis on the offspring of male rats was investigated. The results showed that treatment ranging from 1 to 7 kV caused reduced fertility, but no deaths occurred among the treated animals during the experiment. Observations at 3, 30, 60 and 90 days after exposure showed no recovery of fertility among the treated rats. Treatment with 6 or 7 kV caused congenital anomalies in the offspring, such as micropthalmy, elongation of the foreskin of the penis (praeputium-like), 'rounded face' with omnidirectional hair growth, and narrow pelvis in adult female offspring. The anomalies might be caused by changes to the genetic material in the sperm. The sex ratio of offspring in the experimental groups was not significantly different from normal, suggesting that the number of male and female offspring was unaffected by treatment. The number of offspring with experimentally linked congenital anomalies decreased with time.     

Carbon dioxide laser treatment of vaginal adenosis in DES-exposed offspring: a prospective study

Seventy-nine patients with history and physical findings characteristic of antenatal DES exposure were randomly divided into two groups. Fourty-four DES-exposed offspring had their vaginal adenosis treated with the carbon dioxide laser (group I), and the remaining 35 DES-exposed offspring (group II) did not receive any specific treatment for this condition. Additionally, the 79 DES-exposed offspring were compared to an age-matched control population (group III). Treatment of vaginal adenosis with the carbon dioxide laser did not significantly reduce the incidence of development of new dysplasia in the DES-exposed offspring. This study also showed no statistical difference (p less than or equal to 0.05) in the incidence of dysplasia in DES-exposed offspring as compared to a control population.     

Influence of prenatal waterpipe tobacco smoke exposure on reproductive hormones and oxidative stress of adult male offspring rats

Male infertility is adversely affected by tobacco cigarette smoking. Herein, the effects of prenatal waterpipe tobacco smoke (WTS) exposure on reproductive hormones and oxidative stress of adult offspring rats were evaluated. Pregnant rats received either fresh air or mainstream WTS (2 hr daily). Pregnancy outcomes, circulatory levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin, testicular levels of oestrogen, testosterone and oxidative stress biomarkers [catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS)] were assessed in their adult male offspring rats. Prenatal WTS exposure reduced the number of born offspring, female to pups ratio and birthweight (p < 0.05). Prenatal WTS exposure increased the circulatory levels of FSH and the testicular levels of oestrogen, testosterone and TBARS and catalase activity compared with control group (p < 0.05). However, GPx activity was reduced by WTS exposure (p < 0.05). There appeared to be a trend of increased LH and prolactin levels with prenatal WTS exposure; however, it was not statistically significant compared with control group (p > 0.05). The activity of SOD was not affected by prenatal WTS exposure (p > 0.05). In conclusion, prenatal WTS exposure altered reproductive hormones as well as oxidative stress biomarkers in adult male offspring rats.     

Bone loss in adult offspring induced by low-dose exposure to teratogens

Maternal malnutrition during pregnancy was shown by numerous studies to result in the birth of offspring exhibiting altered bone characteristics, which are indicative of bone loss. We hypothesized that not only maternal malnutrition but also some developmental toxicants (teratogens) given at a dose inducing neither structural anomalies nor growth retardation can detrimentally affect skeletal health in adult offspring. To check this hypothesis, pregnant mice were exposed to a single injection of 5-aza-2-deoxycytidine (5-AZA) (a teratogen capable of inducing phocomelia of the hind limbs) at a sub-threshold teratogenic dose. Micro-computed tomography scanning revealed that femora of 5-month-old male offspring exposed in uterus to 5-AZA had trabecular microarchitecture indicative of bone loss. Furthermore, exposure to 5-AZA increased the susceptibility of offspring to postnatal chronic mild stress, which has been shown to induce bone loss in mice. While exploring possible mechanisms underlying this phenomenon, we observed that the expression of some microRNAs, which have been demonstrated as regulators of key osteoblastogenic genes, was altered in hind limb buds of embryos exposed to 5-AZA. Furthermore, the expression of receptor activator of nuclear factor kappa B ligand (RANKL) in femoral stromal/osteoblastic cells of 5-month-old offspring of 5-AZA-treated females was found to be increased. Collectively, this study implies for the first time that single low-dose exposure to a teratogen can induce bone loss in adult offspring, possibly via alteration of embryonic microRNAs and RANKL expression.     

Risk of IDDM in children of diabetic mothers decreases with increasing maternal age at pregnancy.

Offspring of women with insulin-dependent diabetes mellitus (IDDM) have a significantly lower risk of IDDM than the offspring of men with IDDM. Furthermore, a negative association of the risk of IDDM in the offspring with maternal age at delivery has been reported. This study tested the association with maternal age in an independent set of families (n = 103) in which the mother had at least one pregnancy before and after the onset of IDDM. In the 304 offspring, the mean +/- SE risk of IDDM by age 20 was 6.0 +/- 2.4% for those born at maternal ages less than 25 yr, whereas, the risk was significantly lower (0.7 +/- 0.7%) for those born at older maternal ages (P = 0.03). These 304 offspring were combined with a sample of 1391 offspring previously reported for a multivariate analysis of other factors related to pregnancy. In the combined analysis, the risk of IDDM in offspring born at maternal ages greater than 25 yr was one-fifth that for offspring born to younger mothers. The risk of IDDM in the offspring was not significantly related to birth order, mother's age at first pregnancy, or the interval between pregnancies for subsequent ones. The risk for the children born before the mother's onset of diabetes was higher than that for those exposed in utero to her diabetes, but the difference did not reach statistical significance. In conclusion, although genetic factors are important determinants of susceptibility to IDDM, exposure to maternal diabetes protects offspring from IDDM during the first 2 decades of life.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gestational glucose tolerance and risk of type 2 diabetes in young Pima Indian offspring

The in utero environment is a powerful risk factor for type 2 diabetes in offspring, but little is known about the risk conveyed by nondiabetic gestational glucose levels. This issue was explored in 911 nondiabetic Pima Indian mothers and 1,436 of their children. Associations were assessed in multivariate models between maternal third trimester glucose tolerance and indexes of body composition and glycemic control in their children. At parturition, the mothers' ages ranged from 14 to 43 years. Offspring were studied at age 0-39 years. An SD (1.3 mmol/l) of maternal glucose was associated with 56 g higher birth weight (P = 0.0002). This effect persisted when only offspring of normal glucose tolerant mothers were examined (57 g, P < 0.0001). In Cox proportional hazards models, the adjusted hazard rate ratio for offspring risk of diabetes per SD maternal glucose was 1.6 (95% CI 1.3-2.0, P < 0.0001). When only offspring of normal glucose tolerant mothers were examined, the risk was reduced but remained significant (1.3 [1.04-1.71], P = 0.026). In conclusion, maternal glycemia during pregnancy is associated with increased birth weight and risk of diabetes in Pima Indian offspring, even when mothers are normal glucose tolerant during pregnancy. Thus, prevention of offspring type 2 diabetes may require strategies that focus on improving gestational glucose tolerance even within the normal range.     

Microdissection testicular sperm extraction (micro-TESE) in men with infertility due to nonobstructive azoospermia: summary of current literature

Purpose

Nonobstructive azoospermia (NOA) is associated with intrinsic testicular defects that severely impair sperm production. Although NOA invariably leads to infertility, focal sperm production may exist in the testicles of affected patients, which can be retrieved and used for intracytoplasmic sperm injection (ICSI) to generate healthy offspring. However, geographic locations of testicular sperm producing-areas are uncertain, making microsurgical-guided sperm retrieval (microdissection testicular sperm extraction; micro-TESE) an attractive method to identify and retrieve sperm in patients with NOA due to spermatogenic failure. Given the widespread use of micro-TESE, its effectiveness in harvesting sperm and related potential complications need to be clarified.

Methods

We queried PubMed/MEDLINE for studies published in English, from inception to May 2021, concerning the effect of micro-TESE on sperm retrieval rate (SRR), complication rate and ICSI pregnancy rate—using retrieved testicular sperm in subfertile couples where the male had NOA.

Results

We found 116 articles, including 70 original papers, 32 review articles, and 14 systematic reviews. The evidence accounted for 4895 patients. Micro-TESE retrieved sperm in 46.6% of men with NOA, but SRRs varied considerably (18.4–70.8%) and were mainly related to the treated population characteristics. Concerning the general population of NOA patients who have not undergone previous sperm retrieval (naïve population), the SRR by micro-TESE was 46.8% (1833 of 3914 patients; range 20–70.8%; 28 studies). In studies reporting SR by micro-TESE for men who had failed percutaneous testicular sperm aspiration or non-microsurgical testicular sperm extraction, the SRR was 39.1% (127 of 325 patients; range 18.4–57.1%; 4 studies). Data on adverse events indicated that micro-TESE was associated with low (~?3%) short-term postoperative complication rates. The fertilizing ability of testicular sperm retrieved by micro-TESE and used for ICSI was adequate (~?57%), whereas clinical pregnancy and live birth were obtained in 39% and 24% of couples who had an embryo transfer, respectively. The health of the resulting children seems reassuring, but the evidence is limited. The procedure increases sperm retrieval success compared to non-microsurgical retrieval methods, particularly in men with Sertoli cell-only testicular histopathology.

Conclusion

We concluded that micro-TESE is an effective and safe method to retrieve sperm from men with NOA-related infertility, with potential advantages over non-microsurgical methods. Nevertheless, high-quality, head-to-head comparative randomized controlled trials by sperm retrieval method, focusing on SRR, live birth rate and assessing long-term adverse events and health of children conceived using testicular sperm from NOA patients are lacking. Therefore, further research is required to determine the full clinical implications of micro-TESE in male infertility treatment.