Journal of Human Reproductive Science
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    Table of Contents - Current issue
Coverpage
April-June 2020
Volume 13 | Issue 2
Page Nos. 79-170

Online since Thursday, July 9, 2020

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EDITORIAL  

From the editor's desk Highly accessed article p. 79
Madhuri Patil
DOI:10.4103/jhrs.JHRS_125_20  
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ISAR PAGES Top

Joint IFS-ISAR-ACE recommendations on resuming/opening up assisted reproductive technology services Highly accessed article p. 82
Sudha Prasad, Prakash Trivedi, Neena Malhotra, Madhuri Patil, Dakshinamoorthy Swaminathan, Sanjay Shukla, Kedar Ganla
DOI:10.4103/jhrs.JHRS_109_20  
COVID-19 – A Global challenge on a scale not previously seen. Reproductive care is essential for the well-being of society and therefore the treatment needs to be completely re-thought and individualised. Infectivity and mortality rates are higher than previous pandemics and the disease is present in almost every country. Propagation and containment have varied widely by location and, at present, the timeline to complete resolution is unknown. With successful mitigation strategies in some areas and emergence of additional data, the societies have sanctioned gradual and judicious resumption of delivery of full reproductive care. When we resume, monitor local conditions, including prevalence of disease, status of government or state regulations, and availability of resource. It is important to implement proactive risk assessment within their practices prior to restarting services. One needs to develop clear and modified plans to ensure the ability to provide care while maximizing the safety of their patients and staff. One should also remain informed and stay current regarding new medical findings. These recommendations provide resources for restarting ART practice again.
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REVIEW ARTICLE Top

“The Miracle Mothers and Marvelous Babies”: Psychosocial aspects of surrogacy – A narrative review p. 89
Ansha Patel, Pratap Kumar, P S. V. N. Sharma
DOI:10.4103/jhrs.JHRS_33_20  
Surrogates are described in literature as true angels “who make dreams happen.” On the other hand, surrogacy has also been surrounded by several psychosocial controversies. In this review, we have made an attempt to encapsulate this topic from the multiple perspectives of individuals who are involved in the surrogacy cycle. We present to the readers the various outlooks and dilemmas of the clinicians, patient parties contracting for surrogacy, the child born out of surrogacy, and the intricate role of the mental health professionals in surrogacy arrangements. The review also throws light upon the psychosocial issues in connection to the evolving Surrogacy practices in Indian and in the Western world.
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ORIGINAL ARTICLES Top

CYP19A1 gene expression in patients with polycystic ovarian syndrome p. 100
Roselina Panghiyangani, Purnomo Soeharso, Andrijono , Dwi Anita Suryandari, Budi Wiweko, Mala Kurniati, Dwi Ari Pujianto
DOI:10.4103/jhrs.JHRS_142_18  
Context: Polycystic ovarian syndrome (PCOS) is a common endocrine system disorder among the women of reproductive age, yet the etiology of PCOS remains unclear. Infertility in females with PCOS can be caused by anovulation, high luteinizing hormone levels, and hyperandrogenism. Aims: This research analyzed the role of the aromatase gene (CYP19A1) in PCOS pathogenesis. Settings and Design: This study used an observational, cross-sectional design. Subjects and Methods: A total of 110 research participants (55 PCOS patients and 55 non-PCOS patients) were included in the study. Statistical Analysis Used:A real-time quantitative polymerase chain reaction was used to analyze the mRNA expression for aromatase in granulosa cells. Results: The relative expression of aromatase mRNA is lower in women with PCOS compared to those without PCOS (P<0.05). Relative expression of CYP19A1 (aromatase) mRNA in PCOS group was 0.38 ± 0.25, whereas in non-PCOS group was 1.00 ± 0.00. The decline in aromatase activity contributes to an increase in testosterone level. This condition has a role in hyperandrogenism which is a typical characteristic of PCOS women. Granulosa cells in polycystic ovary undergo disturbance in the development and cannot respond to follicle-stimulating hormone (FSH) stimulation. Lack of stimulation of FSH causes induction inadequacy to aromatase enzyme activity in the aromatization process. The decline in FSH activity is caused by various factors that are associated with typical characteristics of PCOS. Conclusions: There is a decrease in the relative expression rate of granulosa cells’ aromatase mRNA in women with PCOS compared to the non-PCOS.
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Effectiveness of misoprostol in office hysteroscopy in premenopausal nulliparous women: A prospective randomized double-blind placebo-controlled trial p. 104
Vinod G Nair, Kallol Kumar Roy, Rakhi Rai, Anamika Das, Juhi Bharti, Rinchen Zangmo
DOI:10.4103/jhrs.JHRS_149_19  
Study Objective: The objective of this was to evaluate the effectiveness of misoprostol in premenopausal nulliparous women with 200-mcg single vaginal dose 4 h before the procedure. Design: This was a prospective randomized double-blind placebo-controlled trial. Setting: This study was conducted in a tertiary care and academic research center. Patients: One hundred patients were included in the study: 50 in misoprostol group and 50 in placebo. Interventions: Patients underwent office hysteroscopy 4 h after vaginal application of misoprostol or placebo. Measurements and Main Results: Ease of doing hysteroscopy was significantly better in the misoprostol group (difficulty score: 2.74 ± 1.20) as compared to placebo (difficulty score: 4.20 ± 1.10), P = 0.001. The time taken for negotiating the internal os (cervical passage time) was found to be significantly shorter in the misoprostol group (6.20 ± 5.21 s) as compared to placebo (14.78 ± 11.84 s), P = 0.001. The overall Visual Analog Scale (VAS) score was significantly lower in the intervention group (2.64 ± 1.62) as compared to placebo (4.90 ± 1.90), P = 0.001. Moreover, the VAS score at the point of passing internal os was significantly lower in the misoprostol group (2.82 ± 1.39) as compared to placebo (4.94 ± 1.96), P = 0.001. Misoprostol had a significant positive effect on satisfaction level of patients; 76% (n = 38) of women in the misoprostol group expressed their willingness to undergo the procedure again if required versus 18% (n = 9) in placebo, P = 0.001. Furthermore, 78% (n = 39) of women in the misoprostol group would recommend the procedure to their friends and relatives versus 36% (n = 18) in placebo, P = 0.001. Conclusion: Preoperative cervical preparation with 200 mcg of misoprostol vaginal application 4 h before office hysteroscopy in premenopausal nulliparous women significantly reduces the difficulty encountered in negotiating the cervical canal. Further, it significantly reduces the pain experienced by the patient at the point of passage through internal os as well as throughout the entire procedure.
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Body mass index and sperm quality: Is there a relationship? p. 110
Nataliia Mykhailivna Kozopas, Olga Ihorivna Chornenka, Mykola Zinoviyovych Vorobets, Lubov Yevhenivna Lapovets, Hanna Vasylivna Maksymyuk
DOI:10.4103/jhrs.JHRS_15_20  
Context: Obesity and infertility are the major global public health problems. The evidences of adverse impact of adiposity on male fertility are contradictory. Aim: The objective of the study was to determine the effect of overweight and obesity on ejaculate quality, in particular, sperm parameters and biochemical markers. Subject and Design: The study involved 152 men who were distributed into three groups according to the body mass index (BMI, kg/m2): control group with normal values (18.5–24.9), preobese (25.0–29.9), and obese (≥30.0). Materials and Methods: Semen analysis included parameters: volume, sperm concentration and total count, morphology, progressive (PR) and total motility. Levels of fructose, citric acid, and zinc were measured in seminal plasma. Statistic: The results of the studies were analyzed using StatPlus: mac (AnalystSoft Inc., version 6). The Mann–Whitney U-test was used to compare groups. Pearson's correlation coefficient was calculated. P < 0.05 was considered statistically significant. Results: No significant differences of the semen parameters were observed between preobese and control group, except for increasing the number of abnormal spermatozoa. The obese group revealed lower concentration and total number of sperm, PR motility. BMI was negatively correlated with most semen parameters. The overweight group showed a decreasing of fructose levels and increasing of citric acid and zinc concentration, while no significant changes were observed in the obese group, except for a decreasing in fructose. Conclusions: The present study confirms that with the growth of BMI, the sperm quality deteriorates. Based on these results, we can assume that obesity may be an injurious factor of male infertility.
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Role of testicular size as a parameter for predicting infertility in Indian males p. 114
Amit Bellurkar, Sujata Patwardhan, Bhushan Patil, Ajay Kanbur, Hitesh Jain, Rishikesh Velhal
DOI:10.4103/jhrs.JHRS_7_20  
Context (Background): While the semen analysis appears to be the cornerstone in the evaluation of male fertility, the testicular size is a cheap, easy, and convenient to measure yet an ignored parameter for predicting the same. There is insufficient literature for identifying the testicular size cutoff among the Indian men. Aims: The study is aimed to correlate between the testicular volume and length with exocrine testicular function and to set a cutoff size for infertility in Indian men. Settings and Design: The study examined 354 cases over a period of 2 years. The cases comprised 258 men presenting with infertility as well as 96 fertile men as control. Materials and Methods: All the patients had their testes examined using Seager's calipers and Prader's orchidometer, infertile men had their semen analysis. Statistical Analysis: SPSS software and Chi-square test were applied, keeping P < 0.05 statistically significant. Results: The mean testicular volume and length in azoospermic patients were 10.3 ml and 2.4 cm, respectively, whereas in oligoasthenospermic patients they were 13.2 ml and 3.2 cm, respectively. The mean testicular volume, length among cases, and controls were 12.6 ml, 3.2 cm, 18.3 ml and 3.81 cm, respectively. Conclusion: Testicular size correlates significantly with severity of exocrine and endocrine functions. The testicular volume and length average for predicting infertility among Indian men should be 18 ml and 3.8 cm, respectively, unlike the international standards of 20 ml and 4.6 cm.
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Comparing different sperm separation techniques for ART, through quantitative evaluation of p53 protein p. 117
Salvatore Raimondo, Tommaso Gentile, Mariacira Gentile, Francesca Donnarumma, Giusy Esposito, Alessia Morelli, Stefania De Filippo, Felice Cuomo
DOI:10.4103/jhrs.JHRS_117_19  
Context: In the last 10 years, assisted reproductive technologies (ARTs) have offered infertile couples an opportunity to complete their reproductive project. However, the high failure rate could be explained with the complex human reproduction system. In ART, the decrease of the success is due to the conditions far from the natural ones. Aims: The aim of this study is to evaluate deoxyribonucleic acid (DNA) damage of spermatozoa before and after selection procedures, using a new technique able to quantize sperm DNA damage. Settings and Design: They were involved 43 males domiciled permanently in two areas with different Environmental Impact, HEI (high environmental impact) and LEI (Low environmental impact), they are aged between 24 and 31 years with various degrees of dyspermia. Subjects and Methods: The 43 males were divided into two groups: 21 in Group A (EIL) and 22 in Group B (EIH). The samples must be aliquoted into parts of 0.5 mL: Group (a) Control, no processing; Group (b) Swim-up (SUP) from semen; Group (c) classic SUP; Group (d) density gradient centrifugation (DGC). All samples were subjected to a quantitative dosage of p53 protein, before and after processing. Statistical Analysis Used: For the development of the probability and significance of the data, the Student's t-test was used. Results: From our data, it emerges that Groups D and B provide a superior quality about motility, vitality, and apoptosis indexes compared to other conventional techniques. In Group B, apoptosis is comparable to Group D, but they have slightly lower about motility and vitality. Group C is the one that has lower parameters than the other techniques. Regarding the evaluation of p53 protein, the results are conflicting with the evaluation of apoptosis; in fact, in Group D, the values are significantly higher than the other techniques. Conclusions: Sperm separation is an important moment in ART techniques. From our data, it emerges a greater fragility of DNA in the male spermatozoa who reside permanently in areas with high environmental impact.
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A comparative study of the efficacy of levosulpiride versus paroxetine in premature ejaculation p. 125
Manish Bathla, Shazia Anjum, Angad Harshbir Singh, Vinutha Ramesh, Parul Gupta, Leezu Bhusri
DOI:10.4103/jhrs.JHRS_155_19  
Background: Premature ejaculation (PME) can be defined as a lack in the normal voluntary control over ejaculation. It is the most common sexual dysfunction encountered by the male populace. In general, these patients presents with distress. Hence, a novel treatment to eliminate their problem is required. Although the role of SSRI has already been established, the high discontinuation rate and other types of sexual dysfunctions associated with SSRIs reduce their efficacy in controlling this menace. Levosulpiride is a new drug indicated in treatment of PE. Aims and Objectives: The objective is to study the efficacy of levosulpiride; paroxetine and their comparison in patients of PE. Methodology: Index of premature ejaculation (IPE) and intravaginal ejaculation latency time (IELT) were used. A total of 36 patients (18 in each group) were included. The patients were assessed at baseline; at 4 weeks’ and at 8 weeks’ interval. Results: On comparison the score of IPE in domains of ejaculation control, sexual satisfaction, and the total score of IPE were statistically significant on all the three visits. However, the distress score of IPE and the IELT score were statistically not significant between the two groups. Conclusion: No doubt both agents are efficacious in patients of PME but paroxetine is more efficacious than levosulpiride. At the same time, levosulpiride is a lesser studied and used drug hence more research should be done for it.
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The effect of human chorionic gonadotropin on the In vitro development of immature to mature human oocytes: A randomized controlled study p. 133
Chananya Tantitham, Sitanan Panunumpa, Chonthicha Satirapod
DOI:10.4103/jhrs.JHRS_1_20  
Context: In controlled ovarian hyperstimulation cycles, 15% of oocytes have been proven to be immature. Key factors include failure in signal transmission from the cumulus cell to the oocyte, insufficient level of luteinizing hormone, and internal conditions of the oocyte itself. Aims: The aim of the present study was to investigate the effect of human chorionic gonadotropin (hCG) on the in vitro maturity of partially cumulus-denuded immature oocytes collected after controlled ovarian stimulation for in vitro fertilization (IVF). Settings and Design: This was a prospective, randomized controlled design at the department of obstetrics and gynaecology, university hospital. Subjects and Methods: Infertile women underwent gonadotropin-releasing hormone antagonist stimulated protocol for IVF with final maturation triggered by hCG, partially cumulus-denuded immature human oocytes were allocated to two groups: the first was treated with fertilization medium and the second was treated with fertilization medium and hCG. They were cultured for 24 h. Outcomes measured were the oocyte maturation rates to metaphase II (MII) and glucose-6-phosphate dehydrogenase (G6PD) activity of in vitro maturation (IVM) mature oocytes which represent the oocyte quality. Statistical Analysis Used: The Mann–Whitney U-test and One-way ANOVA were used to compare continuous variables, and Chi-square was used for categorical data. Results: In all, 250 immature stimulated oocytes were allocated (125 per group). The maturation rate was higher in the hCG supplement group (48% vs. 39.2%) without significance. The positive brilliant cresyl blue results among the MII oocytes developed from the metaphase I (MI) were significantly higher in the hCG group (P = 0.001). Conclusions: Rescue IVM in fertilization culture medium plus hCG was slightly better than that in the only fertilization culture. MII oocytes developed from MI in hCG supplemented medium had a higher quality based on the measured G6PD activity.
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In vitro Activation of mouse oocytes through intracellular Ca2+ regulation p. 138
Nining Handayani, Budi Wiweko, Sarah Chairani Zakirah, Arief Boediono
DOI:10.4103/jhrs.JHRS_122_19  
Background: Ca2+ signaling pathway is suggested to play an essential role in mediating oocyte maturation. Aims: The aim of this study was to evaluate intracellular Ca2+ of resistant immature oocytes that failed to resume meiosis following subsequent in vitro culture reach metaphase II after calcium ionophore A23187 activation. Settings and Design: This in vitro analytical experimental study was conducted at Animal Science Laboratory of Indonesian Medical Education and Research Institute (IMERI), Human Reproductive Infertility and Family Planning of IMERI, and Electrophysiology Imaging of Terpadu Laboratory, Faculty of Medicine, University of Indonesia. Methods: A total of 308 oocytes classed as resistant immature following in vitro culture were randomly allocated to control (n = 113) and treatment groups (n = 195). The oocyte activation group was exposed to A23187 solution for 15 min and then washed extensively. Maturation was evaluated by observing the first polar body extrusion 20‒24 h after A23187 exposure. Ca2+ imaging was conducted using a confocal laser scanning microscope to identify the dynamic of Ca2+ response. Statistical Analysis: SPSS 20, Chi-square, and Mann–Whitney U-test were used in this study. Results: Activation of resistant immature oocytes with A23187 significantly increased the number of oocyte maturation compared with the control group (P<0.001). Furthermore, fluorescent intensity measurements exhibited a significant increase in the germinal vesicle stage when activated (P = 0.005), as well as the metaphase I stage, even though differences were not significant (P = 0.146). Conclusion: Artificial activation of resistant immature oocyte using chemical A23187/calcimycin was adequate to initiate meiosis progress.
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Relevance of split In vitro fertilization-intracytoplasmic sperm injection method of insemination in normozoospermic and mildly oligospermic men: A retrospective study p. 145
Geeta Goswami, M Devi Gouri
DOI:10.4103/jhrs.JHRS_19_19  
Background: Use of intracytoplasmic sperm injection (ICSI) is generally considered redundant in cases of normozoospermia, or mild male factor cases of infertility and conventional method of insemination is advocated. However, there is a risk of low fertilization or total fertilization failure (TFF) and to avoid this, split in vitro fertilization (IVF)-ICSI method of insemination is advised. In our study, we have shown that not only TFF is avoided with split method of insemination, but also cancellation of embryo transfer (ET) can be avoided in a significant number of IVF cycles. Aims: This study aimed to assess whether the IVF-ICSI split insemination method was able to reduce the risk of ET cancellation in couples with normal or mild sperm characteristics. Settings and Design: It is a retrospective study including a total of 107 split insemination cycles done at our center. Materials and Methods: The female partner's age was under 37 years, and at least ten oocytes were retrieved in all cycles. Sibling oocytes were randomly allocated to IVF or ICSI. Statistical analysis was carried out using Graphpad Prism, Instat. Results and Conclusion: The fertilization rate in oocytes kept in conventional IVF was significantly higher (79.8%) compared to that of oocytes injected through ICSI (69.1%). Only one couple had TFF. In majority of the cycles, i.e., 97 out of 107 cycles, the mode of insemination did not affect the fertilization rate or embryo quality. Nearly 28% of the cycles were saved from ET cancellation by adopting the split insemination method. “Split IVF-ICSI” approach can save a significant number of ART cycles and is found to be cost-effective as it avoids incurring the cost of two ART cycles.
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Follicular flushing versus direct aspiration at oocyte retrieval in poor responders undergoing in vitro fertilization: A randomized controlled trial p. 150
Neena Malhotra, Chithira Pulimoottil Vignarajan, Disket Dolkar, Reeta Mahey, Perumal Vanamail
DOI:10.4103/jhrs.JHRS_59_19  
Aim: This study aims to study the effect of follicular flushing at oocyte retrieval on Assisted Reproductive Technique (ART) outcomes in poor responders undergoing in vitro fertilization. Settings and Design: A prospective randomized controlled trial was conducted in the ART center of our hospital. Materials and Methods: A total of 71 patients who responded poorly during controlled ovarian stimulation were recruited. Patients were randomized to follicular flushing or to direct aspiration group. The primary outcomes of the study were the total number of oocytes retrieved and the number of metaphase (M II) oocytes retrieved. Secondary outcomes were anesthesia time, procedure time, fertilization rate, cleavage rate, total number of embryos, number of embryos transferred, number of Grade 1 embryos, failed oocyte recovery, failed fertilization, implantation rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Statistical Analysis Used: Chi-square test and Student's t-test. Results: The total number of oocytes retrieved, number of M II oocytes, fertilization rate, cleavage rate, total number of embryos, number of Grade 1 embryos, failed oocyte recovery, failed fertilization, implantation rate, miscarriage rate, and live birth rate were comparable between the two groups. The anesthesia and procedure time was significantly higher in the flushing group. Conclusions: Follicular flushing does not result in a significant improvement in the ART outcomes despite increasing procedure and anesthesia times.
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The influence of delayed blastocyst development on the outcome of frozen-thawed transfer of euploid and untested embryos p. 155
Parnita Sardana, Jwal Banker, Reena Gupta, Aditi Kotdawala, P G. L. Lalitkumar, Manish BankerIntroduction
DOI:10.4103/jhrs.JHRS_115_19  
Objective: The primary objective is to compare live birth rates (LBRs) following frozen embryo transfer (FET) of euploid day 5 with day 6 blastocysts. We also compared LBRs following FET of untested blastocysts vitrified on day 5 and day 6 in self-oocyte and ovum donation (OD) cycles. Design: This was a retrospective observational study. Setting: Nova IVF Fertility, Ahmedabad. Materials and Methods: Ninety-seven FET using self-oocytes following preimplantation genetic testing A (PGT-A), 464 FET following OD, and 907 FET using self-oocytes without PGT-A testing between January 2016 and December 2017 were included in this study. Main Outcome Measures: LBR following FET in day 5 versus day 6 blastocysts in euploid embryos using self-oocytes and in untested embryos using both self and donor oocytes. Results: In PGT-A cycles, no statistically significant difference was observed in LBRs following transfer of euploid blastocysts developed on day 5 or day 6 (D5: 53%; D6:40%, P = 0.83). However, the LBRs with day 5 blastocysts were higher compared with day 6 group in untested group using both self and donor oocytes (self D5: 52.7%; D6: 38.2%; P = 0.001 and OD D5: 44.7%; D6: 29.8%; P = 0.001). Miscarriage rates were comparable in both the groups.Conclusions: The present study demonstrated comparable pregnancy outcomes following FET of euploid embryos vitrified on day 5 and day 6. However, higher LBRs were reported in day 5 group in untested embryos.
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CASE SERIES Top

Isolated fallopian tube torsion: A rare twist with a diagnostic challenge that may compromise fertility p. 162
Devi Balasubramaniam, Kavitha Yogini Duraisamy, Malathi Ezhilmani, Saranya Ravi
DOI:10.4103/jhrs.JHRS_143_19  
Isolated Fallopian tube torsion (IFTT) is a rare entity with utmost important gynecological emergency with difficult preoperative diagnosis. Our aim is to analyze the clinical presentation, risk factors, and management of IFTT. We retrospectively analyzed all patients with intraoperative diagnosis of IFTT in our endogynecological department over a time period of 3 years and 6 months (January 2015–June 2018) in a tertiary level laparoscopic center. The clinical profile of the patients was analyzed and the results formulated. Statistical analysis was done by SPSS system, Version 15.00 (SPSS Inc., Chicago). A total 17 cases were diagnosed with IFTT with or without pathology. The mean age was 28.07 ± 11.3 years. Lower abdominal pain was the most common symptom (88%). About 47% had a history of tubal ligation. Salpingectomy was done in the majority of the patients (82.3%). Detorsion and preservation of the tube was possible in 17.6% of the cases. High index of suspicion is needed to diagnose this rare cause of acute abdomen. Hence, an early intervention can enhance the salvageability of the affected tubes which has a positive impact on the fertility status of the patients. Tubal preservation is the preferred procedure of choice whenever feasible.
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CASE REPORT Top

“Through Thick and Thin:” Morphological spectrum of epididymal tubules in obstructive azoospermia p. 168
Aditya Prakash Sharma, Jeni Mathew, Japleen Kaur, Sudheer Kumar Devana
DOI:10.4103/jhrs.JHRS_22_20  
Morphological appearance of the epididymal tubules encountered at the time of microsurgical vasoepididymal anastomosis (VEA) is quite variable. They are the indicators of underlying etiology as well as guide further course of management. We present three cases of obstructive azoospermia with three different morphologies encountered during the microsurgical VEA. As the etiologies encountered in our setup are different from that of the western world, this report highlights the morphological variation of tubules encountered in our subpopulation. This also helps us in deciding the customization of microsurgical VEA accordingly.
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