Comparison of intracytoplasmic sperm injection (ICSI) outcomes in infertile men with spermatogenic impairment of differing severity / 亚洲男科学杂志(英文版)

The extent of spermatogenic impairment on intracytoplasmic sperm injection (ICSI) outcomes and the risk of major birth defects have been little assessed. In this study, we evaluated the relationship between various spermatogenic conditions, sperm origin on ICSI outcomes, and major birth defects. A total of 934 infertile men attending the Center for Reproductive Medicine of Ren Ji Hospital (Shanghai, China) were classified into six groups: nonobstructive azoospermia (NOA; n = 84), extremely severe oligozoospermia (esOZ; n = 163), severe oligozoospermia (sOZ, n = 174), mild oligozoospermia (mOZ; n = 148), obstructive azoospermia (OAZ; n = 155), and normozoospermia (NZ; n = 210). Rates of fertilization, embryo cleavage, high-quality embryos, implantation, biochemical and clinical pregnancies, abortion, delivery, newborns, as well as major birth malformations, and other newborn outcomes were analyzed and compared among groups. The NOA group showed a statistically lower fertilization rate (68.2% vs esOZ 77.3%, sOZ 78.0%, mOZ 73.8%, OAZ 76.6%, and NZ 79.3%, all P < 0.05), but a significantly higher implantation rate (37.8%) than the groups esOZ (30.1%), sOZ (30.4%), mOZ (32.6%), and OAZ (31.0%) (all P < 0.05), which was similar to that of Group NZ (38.4%). However, there were no statistically significant differences in rates of embryo cleavage, high-quality embryos, biochemical and clinical pregnancies, abortions, deliveries, major birth malformations, and other newborn outcomes in the six groups. The results showed that NOA only negatively affects some embryological outcomes such as fertilization rate. There was no evidence of differences in other embryological and clinical outcomes with respect to sperm source or spermatogenic status. Spermatogenic failure and sperm origins do not impinge on the clinical outcomes in ICSI treatment.

Predictive value of FSH, testicular volume, and histopathological findings for the sperm retrieval rate of microdissection TESE in nonobstructive azoospermia: a meta-analysis / 亚洲男科学杂志(英文版)

We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.

single-center study examining the outcomes of percutaneous epididymal sperm aspiration in the treatment of obstructive azoospermia

Obstructive azoospermia [OA] is characterized by normal spermatogenesis and the absence of sperm in the ejaculate. Variable success rates have been reported using in-vitro fertilization [IVF] combined with PESA in cases of men with OA. To determine fertilization and pregnancy outcomes from PESA-derived spermatozoa and to ascertain whether frozen spermatozoa yields similar outcomes compared to fresh specimens. The charts of 68 consecutive couples undergoing 68 cycles of sperm retrieval for OA over eight years [2002-2010] were retrospectively reviewed. Patients requiring testicular intervention were excluded [n = 17]. Viable sperms were identified in 100% of men, and fresh spermatozoa were obtained in 40 patients [78.4%] simultaneously with female egg retrieval. The average fertilization rate was 77.7% with five embryos not surviving to transfer [12.5%]. Pregnancies were confirmed in 48.6% [17/35]. Twin gestations occurred in 11.8% [2/17] of cases. Frozen-thawed spermatozoa were used in 11 patients [21.6%]. In this subgroup, the average fertilization rate was 73.6% with pregnancies confirmed in 54.5% [6/11]. No multiple gestations were generated, and no complications occurred. The use of fresh spermatozoa for PESA provided no significant improvements in outcomes over frozen specimens. PESA is a very effective, simple, and safe method of obtaining spermatozoa for IVF. Outcomes obtained using fresh and frozen PESA-derived spermatozoa were similar and as such, either could be used during the IVF process

Azoospermia y fertilización asistida: rol de la histología testicular en el éxito de icsi / Azoospermia and assisted reproduction: role of testicular histology in the success of ICSI

Introducción: La infertilidad masculina afecta aproximadamente al 7por ciento de los hombres, presentándose hasta el 15 por ciento de ellos con azoospermia. El conocimiento del tipo de azoospermia (obstructiva o no obstructiva) y la localización de la falla (pre-testicular, testicular o post-testicular) es vital para conocer el pronóstico de fertilidad de la pareja y plantear un plan terapéutico adecuado. Actualmente, la extracción de espermatozoides desde epidídimo o testículo de pacientes azoospérmicos, y la posterior inyección intracitoplásmática de éstos (ICSI, por sus siglas en inglés) ha permitido obtener embriones viables para su posterior transferencia. Materiales y métodos: Estudio descriptivo retrospectivo de 42 parejas infértiles con diagnóstico de azoospermia; que se sometieron a biopsia testicular, ICSI y posterior transferencia de embriones, entre los años 2004 y 2012. Se lleva a cabo un análisis de la edad de los pacientes, resultados de la histopatología testicular y su asociación con los resultados de la fertilización asistida. Resultados: 42 pacientes azoospérmicos se sometieron a biopsia testicular y extracción de espermatozoides en el mismo acto quirúrgico. La edad promedio de los pacientes fue de 36 años para los hombres y 32 años para las mujeres. En el análisis histológico de los tejidos testiculares, el 31por ciento de los pacientes presentaban espermatogénesis conservada (EC), el 35.7 por ciento atrofia mixta (AM), el 14.3 por ciento hipoespermatogénesis (HE), el 14.3 por ciento detención de la maduración (DM) y un 4.8 por ciento presentaba otras histologías. Lograron embarazo clínico 14 de 42 parejas (33,3 por ciento), siendo la tasa de embarazo específica por patología de 38,5 por ciento para EC, 26.7 por ciento para AM, 50 por ciento para HE, 16,7 por ciento para DM y 50 por ciento para las otras histologías. 12 de las 42 parejas realizaron más de un ciclo de transferencias...

Introduction: Male infertility affects approximately 7percent of men, presenting up to 15 percent with azoospermia. Knowing the type of azoospermia (obstructive or non-obstructive) and the location of the problem (pre-testicular, testicular and post-testicular) is vital to recognize the fertility prognosis of the couple and present a proper treatment plan. Currently, the extraction of sperm from epididymis or testis of azoospermic patients, and subsequent intracytoplasmic sperm injection (ICSI) has yielded viable embryos for transfer. Materials and Methods: Retrospective study of 42 infertile couples diagnosed with azoospermia, who underwent testicular biopsy, ICSI and subsequent embryo transfer, between 2004 and 2012. We performed an analysis of the patients’ age, testicular histopathology results and their association with assisted fertilization outcome. Results: 42 azoospermic patients underwent testicular biopsy and sperm extraction in the same surgery. The average age of patients was 36 years for men and 32 years for women. Histologic analysis of testicular tissue showed that 31 percent of patients had normal spermatogenesis (NS), 35.7 percent mixed atrophy (MA), 14.3 percent hypospermatogenesis (HS), 14.3 percent maturation arrest (MTA) and 4.8 percent had other histologies. 14 of 42 couples achieved clinical pregnancy (33.3 percent), with a specific pregnancy rate of 38.5 percent for NS, 26.7 percent for MA, 50 percent for HS, 16.7 percent for MTA and 50 percent for other histologies. 12 of 42 couples underwent more than one transfer cycle. Conclusions: The use of ICSI is a suitable alternative for infertile couples with severe male factor. The results of this technique are favorable for most histologies. Patients with MA exhibit sertoli solo syndrome and / or tubular sclerosis foci associated to regions with normal spermatogenesis, enabling the sperm extraction for ICSI.

Predictive factors for sperm retrieval and sperm injection outcomes in obstructive azoospermia: do etiology, retrieval techniques and gamete source play a role?

Obstructive azoospermia is a relatively common male infertility condition. The main etiologies of obstructive azoospermia include congenital, surgical-derived, traumatic and post-infectious cases. Although seminal tract reconstruction is a cost-effective treatment in most cases, this approach may not be feasible or desired in some cases. In such cases, assisted reproduction techniques offer a method for achieving pregnancy, notably via sperm retrieval and intracytoplasmic sperm injection. This process requires several considerations and decisions to be made, including the cause and duration of obstruction, which sperm retrieval technique to use, and whether to use fresh or frozen-thawed sperm. We present a review of obstructive azoospermia and assisted reproduction techniques, highlighting the most relevant aspects of the decision-making process for use in clinical practice.

Reproductive outcomes, including neonatal data, following sperm injection in men with obstructive and nonobstructive azoospermia: case series and systematic review

We compared pregnancy outcomes following intracytoplasmic sperm injection for the treatment of male infertility according to the type of azoospermia. First, we analyzed our data from 370 couples who underwent intracytoplasmic sperm injection using sperm from men with obstructive azoospermia and nonobstructive azoospermia, and the outcomes were compared to a group of 465 non-azoospermic infertile males. Then, we performed a systematic review of the published data on pregnancy and neonatal outcomes of children born after sperm injection using sperm from men with obstructive and nonobstructive azoospermia. Live birth rates were significantly lower in the nonobstructive azoospermia group (21.4%) compared with the obstructive azoospermia (37.5%) and ejaculated sperm (32.3%) groups. A total of 326 live births resulted in 427 babies born. Differences were not observed between the groups in gestational age, preterm birth, birth weight and low birth weight, although we noted a tendency towards poorer neonatal outcomes in the azoospermia categories. The overall perinatal death and malformation rates were 2.8% and 1.6%, respectively, and the results did not differ between the groups. We identified 20 published studies that directly compared pregnancy outcomes between obstructive azoospermia and nonobstructive azoospermia. Most of these studies were not designed to detect differences in live birth rates and had lower power to detect differences in less frequent outcomes, and the reporting of neonatal outcomes was unusual. The included studies reported either a decrease or no difference in pregnancy outcomes with intracytoplasmic sperm injection in cases of nonobstructive azoospermia and obstructive azoospermia. In general, no major differences were noted in short-term neonatal outcomes and congenital malformation rates between children from fathers with nonobstructive azoospermia and obstructive azoospermia.

Enzymatic digestion improves testicular sperm retrieval in non-obstructive azoospermic patients

In patients with non-obstructive azoospermia [NOA], vital spermatozoa from the tissue is obtained from testes by enzymatic treatment besides the mechanical treatment. To increase the sperm recovery success of testicular sperm extraction [TESE], with enzymatic digestion if no sperm is obtained from testis tissue by mechanical method. Tissue samples were collected from 150 men who presented with clinical and laboratory data indicating NOA by means of TESE and micro dissection TESE methods. Initially, mature spermatozoa were examined for by mechanical extraction technique shredding the biopsy fractions. In cases whom no spermatozoa was observed after maximum 30 min of initial searching under the inverted microscope, the procedure was followed by enzymatic digestion using DNaseI and collagenase type IV. Surgery type, pathology, AZF, karyotype, hormones and testis size were compared in patients. Of 150 cases with NOA, conventional mincing method extended with enzymatic treatment yielded successful sperm recovery in 13 [about 9%] patients. Comparison of parameters revealed that level of FSH and LH were significantly different [p=0.04 and 0.08 respectively] between two groups that response negative and positive to enzymatic digestion. The combination of conventional TESE and enzymatic digestion is an effective method to recover spermatozoa. The benefit of the mincing combined with enzyme to sperm retrieval for NOA firstly shorten the mechanical searching time, leading to minimizing further cellular damage as well as exposure to external conditions, and secondly reduce the number of cases with sperm recovery failures. Also, the serum level of FSH and LH are factors that influence the chance of sperm retrieval

[Evaluation of Spermatogenesis in non-obstructive azoospermic patients with histopathological and cytological methods]

The ability to use only a few spermatozoa using testicular biopsy and by microinjection technique to achieve fertilization and pregnancy has revolutionized the potentials to treat patients suffering from azoospermia. However, spermatogenesis is defective in men with non-obstructive azoospermia [NOA] resulting in failure to detect spermatozoa. In order to achieve a more sensitive and reliable method for detecting sperm/spermatid in testes of NOA patients, we compared histopathological and cytological methods. Eighty six NOA patients were included in a prospective study. History taking, physical examination and hormonal profile [including FSH] were done initially. Thirty six patients had testis pathology report before enrolling in to our study. The patients underwent multiple bilateral testis biopsies until successful retrieval of sperm/spermatid. Half of each biopsy specimen underwent cytological evaluation [mechanical and enzymatic] and the other half was sent for pathological evaluation [TBX]. The male and female mean ages were 37 [25-59] and 32 [23-42] years, respectively. The mean infertility duration was 7 years. The mean volume of right and left testis were 16.4 and 16.2 ml, respectively. Mean FSH level was 18.1 +/- 14.2 ml U/ml. In cytology, sperms and spermatids were seen in 65 and 18 patients, respectively and in pathology slides in 51 and 16 patients, respectively. In our study, the relationship between visualizing testicular sperm/spermatid and TESE had sensitivity of 80% and negative predictive value of 15%. Sixty one patients had sufficient number of sperm/spermatid for ICSI and with this treatment fifty seven embryos were transferred and seven clinical pregnancies were observed. In conclusion, in men with non-obstructive azoospermia, TESE is more sensitive and reliable than histopathology evaluation. This means that TESE may help in deciding for treatment of severe male factor infertility, even when histopathologic examination is inconclusive

[ effect of pentoxifylline on motility and morphology of spermatozoa from epididymal and testicular samples of infertile men]

There are generally three factors involved in male infertility: low count, weak motility, and abnormal morphology of spermatozoa. Currently, it is impossible to improve the quality of sperm count and morphology in vitro. However, it may become possible to improve the sperm motility with the application of motility enhancer medicine. The objective of this study was to evaluate the effect of pentoxifylline[PX] on sperm motility and morphology of asthenozoospermic epididymal and testicular samples. The specimens were retrieved with percutaneous epididymal sperm aspiration [PESA] and testicular sperm extraction [TESE] from men with obstructive azoospermia. A total of 40 PESA and 40 TESE samples were allocated to this prospective study. Following preliminary evaluation, each sample was processed with swim up procedure and then divided into two aliquots of control [non -PX] and PX [3.5 mMPX]. Following 45 min of incubation at 37°C, the percentages of motility and normal morphology of spermatozoa were evaluated using Mackler chamber and papaniclau staining techinque, respectively. The mean sperm counts in the PESA and TESE groups were 7.4 +/- 7.3x10[6] and 2.43 +/- 1.3x10[6], respectively. The percentages of normal morphology in the above groups were 22.67 +/- 11.6 and 14.9 +/- 9.2 which were respectively changed to 23.2 +/- 15.7 and 9.5 +/- 1.9 with PX incubation. In addition, the percentage of control progressive motility in the PESA and TESE samples were 13.9 +/- 4.2% and 0.26 +/- 0.6% which were increased to 20.1 +/- 9.7% [p<0.001] and 0.95 +/- 0.03% [p<0.05]. These results strongly suggest that PX was successful in enhancing sperm motility particularly in the PESA group. It also did not have any significant side effect on sperm morphology. PX is considered to be safe and cheap, with easy application which may be used for improving the male infertility treatment program. With its dual role as motility enhancer and vitality detector of spermatozoa, it can be used safely for the ICSI treatment of severe cases of asthenozoospermia

[ Effect of repeated percutaneous epididymal sperm aspiration on sperm parameters of azoospermic patients]

There are a limited number of infertile males with obstructive azoospermia, At present, spermatozoa can be aspirated with a simple technique called, percutaneous epididymal sperm aspiration [PESA]. It is also possible to repeat PESA to aspirate spermatozoa for intracytoplasmic sperm injection [ICSI] cycles. The objective of this study was to evaluate whether of not repeated PESA would cause any obstruction, scars, or defects on sperm parameters. Eighty-nine azoospermic cases were admitted to the university infertility center. A total of 235 PESA who underwent 199 ICSI cycles were selected for this retrospective study. Sperm concentration, motility, and normal morphology, as well as the fertilization rates were statistically evaluated for each time. Sperm concentration [x10[6]/ml] in first to forth PESA was 37.68, 45.58, 35.62, and 19.13, respectively. Sperm motility in the above groups was 24.95%, 23.10%, 23.24%, and 25.71%, respectively. Also, fertilization rate [FR] was 66.36, 68.35, 71.89, and 74.70 percent, respectively, for the same groups. There was not any significant difference in sperm parameters and FR in patients undergoing 1 to 4 PESA. In addition, neither obstruction nor scars were reported in PESA cases. We conclude that repeated PESA is safe and reliable, and does not cause any significant defects in sperm parameters. Also, this technique can be repeated in individuals with obstructive azoospermia to aspirate sperm for a treatments regimen