Journal of Human Reproductive Science
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    Table of Contents - Current issue
Coverpage
January-March 2018
Volume 11 | Issue 1
Page Nos. 1-81

Online since Tuesday, March 27, 2018

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EDITORIAL  

From the editor's desk p. 1
Madhuri Patil
DOI:10.4103/jhrs.JHRS_32_18  PMID:29681708
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REVIEW ARTICLE Top

Mitochondrial donation: A boon or curse for the treatment of incurable mitochondrial diseases Highly accessed article p. 3
Nishtha Saxena, Nancy Taneja, Prakriti Shome, Shalini Mani
DOI:10.4103/jhrs.JHRS_54_17  PMID:29681709
Mitochondria are present in all human cells and vary in number from a few tens to many thousands. As they generate the majority of a cell's energy supply which power every part of our body, and hence, their number varies in different cells as per the energy requirement of the cell. Mitochondria have their own separate DNA, which carries total 13 genes. All of these 13 genes are involved in energy production. For normal functioning of cells, the mitochondria need to be healthy. Unhealthy mitochondria can cause severe medical disorders known as mitochondrial disease. In case of mitochondrial disease, the most commonly affected organs are the heart, kidney, skeletal muscle, and brain. The diseases related to defects in these organs are quite prevalent in the society. Majority of these mitochondrial diseases are caused by genetic defects (mutations) in the mitochondrial DNA. Unlike nuclear genes, mitochondrial DNA is inherited only from our mother. Mothers can carry abnormal mitochondria and be at risk of passing on the serious disease to their children, even if they themselves show only mild or no symptoms. Due to the complex nature of these diseases, their diagnosis and therapy are very difficult. Hence, till now, only the different methods for management of these diseases are known. However, after understanding the complexity related to the cure of these diseases, alternative methods have been developed to minimize/stop the transfer of mitochondrial diseases from mother to offspring. This latest technique is called mitochondrial replacement or “donation.” In the present review, we are discussing the methodological details and issues related to the technique of mitochondrial donation. Our study is also a step toward raising awareness about mitochondrial diseases and advocating for the legalization of mitochondrial donation, a revolutionary in vitro fertilization technique.
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ORIGINAL ARTICLES Top

Possible link between stress-related factors and altered body composition in women with polycystic ovarian syndrome p. 10
Barnali Ray Basu, Olivia Chowdhury, Sudip Kumar Saha
DOI:10.4103/jhrs.JHRS_78_17  PMID:29681710
Background: Stress is an invisible factor affecting modern day living and is strongly associated with many disease pathogenesis including polycystic ovarian syndrome (PCOS) in women. PCOS is the most frequent endocrinological disorder that affects women of reproductive age, leading to metabolic dysfunction and body composition alterations. Salivary amylase and cortisol are major stress mediators that have been implicated in PCOS. However, their role in altering body composition in PCOS is yet to be deciphered. Aim: The present study aimed at understanding the relation between stress-associated factors and alterations in body composition among PCOS patients. Design: This study enrolled a total of 100 patients (PCOS) and 60 age-matched controls. The female patients were of ages between 13 and 30 years. Materials and Methods: Standard assay kits were used to evaluate the α-amylase activity and cortisol level in saliva. The participants were chosen on the basis of the Rotterdam American Society for Reproductive Medicine/European Society of Human Reproduction criteria. Saliva was collected from each participant as per the protocol of Salimetrics, USA. Statistical Analysis: Statistical analysis was performed using SPSS version 20 for Windows. The quantitative variables are described as mean ± standard deviation. P < 0.05 was considered significant. Results: Increased salivary cortisol level and α-amylase activity were seen in the PCOS population as compared to age-matched controls suggesting patients a sustained stress scenario in their system. Moreover, overweight PCOS participants reflected higher amylase activity than the lean patients participants. Pulse rate, body mass index (BMI), visceral adiposity, and waist-hip ratio (WHR) was considerably higher in the PCOS patients participants compared to controls. A significant correlation could be drawn between the α-amylase activity and BMI or WHR, respectively, among PCOS patients. These observations indicate a strong link between the stress marker and alterations in the body composition parameters of PCOS patients participants. Conclusion: Higher prevalence of stress in PCOS patients participants has a critical role in their altered body composition.
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Diagnostic hysterolaparoscopy for evaluation of infertility: Our experience in a tertiary Care Hospital p. 19
Sairem Mangolnganbi Chanu, Gouri Sankar Rudra Pal, Subrat Panda, AS Santa Singh
DOI:10.4103/jhrs.JHRS_114_16  PMID:29681711
Objective: The objective of this study is to analyze the role of diagnostic hysterolaparoscopy (DHL) for evaluation of infertility in a tertiary care hospital. Materials and Methods: This retrospective study was conducted from July 2014 to June 2016. Results: Out of 151 patients, 58.28% and 41.72% had primary and secondary infertility, respectively. In primary infertility group 37.5% and in secondary infertility group 49.2% had abnormal findings. Most common finding was adnexal adhesions (pelvic inflammatory disease) and laparoscopic findings were more common than the hysteroscopic ones. Conclusion: DHL was helpful in finding some reversible causes of infertility such as adnexal adhesions, tubal blockade, and uterine synechiae, etc.
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Effectiveness of anti-mullerian hormone-tailored protocol compared to conventional protocol in women undergoing in vitro fertilization: A randomized controlled trial p. 24
Sumi Thomas, Mousumi Acharya, K Muthukumar, Achamma Chandy, Mohan S Kamath, TK Aleyamma
DOI:10.4103/jhrs.JHRS_55_17  PMID:29681712
Background: Assessment of ovarian reserve before an in vitro fertilization cycle (IVF) is one among the many factors that predicts a successful cycle. Individualized protocol based on ovarian reserve is designed to optimize the pregnancy outcome without compromising the patient safety. Although authors have shown that anti-Mullerian hormone-tailored (AMH) protocols have reduced the treatment burden and improved pregnancy rates, a few others have questioned its efficacy. Aims: The aim of this study was to decide whether the AMH-tailored protocol or the conventional protocol better decides IVF outcomes. Setting and Design: Prospective randomized controlled trial conducted at a tertiary level university hospital. Materials and Methods: Patients undergoing their first IVF cycle who fulfilled the inclusion criteria were recruited and randomized to each group. Serum follicle-stimulating hormone was done for the patients on day 2 or 3 of a prior menstrual cycle, and serum AMH was done in the preceding cycle. Statistical Analysis: Analysis was performed using SPSS software version 16. Results and Conclusion: There were 100 patients in each group. A total of 83 patients underwent embryo transfer in the conventional group and 78 patients in the AMH group. The clinical pregnancy rates per initiated cycle (36.4% vs. 33.3%) and per embryo transfer (45.1% vs. 41.3%) were similar in both the groups. There was no statistical difference in the number of cycles cancelled due to poor response or the risk of ovarian hyperstimulation syndrome in both the groups. Hence, this study showed the similar effectiveness of AMH-tailored protocol and conventional protocol in women undergoing IVF.
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Does pretrigger echogenic endometrium in assisted reproductive technology cycles reflect raised serum progesterone level? p. 29
Monna Pandurangi, N Sanjeeva Reddy, G Usha Rani, Hepzibha Kirubamani
DOI:10.4103/jhrs.JHRS_104_17  PMID:29681713
Background: Serum progesterone is the main hormone of the luteal phase. The hyperechoic pattern of the endometrium in the luteal phase is believed to be induced by raised serum progesterone. Serum progesterone is found to be raised cases of controlled ovarian stimulation (COS) cycle on the day of ovulation trigger. Aim: This study aims to find the association between echogenicity of endometrium and raised serum progesterone Objective: The objective of this study is to determine whether raised pretrigger serum progesterone influences the echogenicity of the endometrium Materials and Methods: In this prospective observational study, we evaluated 221 patients who underwent COS. Echogenic patterns of the endometrium on transvaginal sonography were described as hypoechoic/trilaminar endometrium (Type A), isoechoic (Type B), and hyperechoic (Type C). The endometrial pattern and serum progesterone levels were evaluated on the day of ovulation trigger and value of ≥1 ng/ml was considered as elevated. Results: A total of 168 patients out of 221 patients (76.01%) had elevated serum progesterone levels on the day of ovulation trigger. Type A endometrium was found in a total of 174 patients, of these 132 patients (75.86%) had raised serum progesterone. Type B endometrium was found in 35 patients, of these 27 patients (77.14%) had raised serum progesterone. Type C endometrium was seen in 12 patients, out of these 9 patients (75.00%) had raised serum progesterone level. There was no statistically significant difference in the echogenic patterns of endometrium in patients with raised progesterone (≥1 ng/ml). On intergroup comparison, the difference in the progesterone levels between type A and type C was statistically significant (P = 0.02), and on receiver operating characteristic curve analysis, echogenic endometrium was found to predict progesterone level of 1.57 ng/ml with a sensitivity of 58.3% and specificity of 58.4% only. Conclusion: Echogenicity of the endometrium does not reliably predict raised serum progesterone on the day of ovulation trigger.
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Tamoxifen is better than low-dose clomiphene or gonadotropins in women with thin endometrium (<7 mm) after clomiphene in intrauterine insemination cycles: A prospective study p. 34
Sunita Sharma, Geetha Rani, Gunja Bose, Indranil Saha, Sikha Bathwal, BN Chakravarty
DOI:10.4103/jhrs.JHRS_9_17  PMID:29681714
Aim: Gonadotropin stimulation is used as the second line of treatment in patients with thin endometrium following clomiphene citrate (CC) administration, which is associated with higher cost, multiple births, and ovarian hyperstimulation syndrome. Tamoxifen (TMX), a selective estrogen receptor modulator, acts as an agonist on the endometrium. The objective of the present study was to compare the efficacy of low-dose CC, TMX, and gonadotropins in women with thin endometrium (<7 mm) following Clomiphene in intrauterine insemination (IUI) cycles. Settings and Design: A prospective observational study between December 2011 and June 2013 was carried out in a tertiary infertility center. Methods: Women (n = 502) undergoing IUI with endometrium <7 mm after 100 mg CC were included in the study and divided into three treatment groups. Women in Group A (n = 182, cycles = 364) received clomiphene (50 mg/day from day 3 to 7), Group B (n = 179, cycles = 342) received TMX (40 mg/day from day 3 to 7), and Group C (n = 141, cycles = 226) received continuous urine-derived follicle-stimulating hormone 75–150 IU from day 3 onward until human chorionic gonadotropin injection. Endometrial thickness (ET), pregnancy rate, and live birth rate were considered as main outcome measures. Statistical Analysis: Multiple comparisons using one-way ANOVA and Schiff's test were performed. Results: Pregnancy and live birth rate were significantly higher (P < 0.004) in TMX and gonadotropin groups compared to clomiphene. A number of follicles in the TMX group were found to be lower (P < 0.001) compared to other two groups. In polycystic ovary syndrome patients, ovulation induction with TMX resulted in inadequate response in more than half of the cycles. Conclusions: TMX can improve ET and live birth rate in patients with thin endometrium after clomiphene.
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Can intracytoplasmic morphologically selected spermatozoa injection be used as first choice of treatment for severe male factor infertility patients? p. 40
Geeta Goswami, Meeta Sharma, Deepika Jugga, Devi M Gouri
DOI:10.4103/jhrs.JHRS_74_17  PMID:29681715
Aim: This study was carried out to assess the outcome of the intracytoplasmic morphologically selected sperm injection (IMSI) technique compared with the previous failed intracytoplasmic sperm injection (ICSI) attempts in oligoasthenoteratozoospermia (OAT)/severe OAT (SOAT)/teratozoospermia patients. Setting: Institution-based, in vitro fertilization center. Study Design: It was a nonrandomized prospective study including 57 couples who had previous one or two ICSI failures (failure due to no implantation as embryos were transferred in these cycles and had no pregnancy) due to male factor. There was no case of total fertilization failure. IMSI was carried out in these couples and the results were compared with their previously failed ICSI attempts. Materials and Methods: Real-time selection of sperms was done using IMSI as it allows the assessment of fine nuclear morphology and vacuoles in the sperm head at a high magnification (>6000×) with differential interference contrast optics. Therefore, IMSI was applied in couples having OAT, SOAT or teratozoospermia as male factor and the results were compared with their previous failed ICSI attempts. Statistical analysis was carried out using GraphPad Prism. Results and Conclusion: Data analysis demonstrated significant difference in the fertilization rate between IMSI and previous ICSI attempts of these patients (30.0% vs. 52.0%; P < 0.05). The embryo quality, implantation and pregnancy rates with IMSI were also significantly higher than those of their previous ICSI cycles (32% vs. 56.4%; 30.2% vs. 68.5%; 0.0% vs. 62.4%; P < 0.05). Our conclusion is that the IMSI procedure improved embryo development and the clinical outcomes in the same infertile couples with male infertility and poor embryo development over their previous ICSI attempts and can be taken up as the treatment of choice in cases of severe male factor infertility.
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Equivalency of in vitro fertilization success rates in elective single blastocyst transfer and elective double blastocyst transfer: An example of equivalence methodology in clinical reproductive health p. 45
Marni B Jacobs, Hillary Klonoff-Cohen, V Gabriel Garzo
DOI:10.4103/jhrs.JHRS_136_17  PMID:29681716
Context: When comparing success rates between treatments, it is more appropriate to structure analyses in terms of equivalence rather than traditional analyses that assess differences. Unfortunately, no studies of elective single blastocyst transfer (eSBT) have been conducted in this manner. Aims: The objective of this study was to assess clinical equivalence of in vitro fertilization success rates among patients undergoing eSBT. Settings and Design: A historical prospective study was conducted at a private fertility center. Methods: Medical records were reviewed to identify patients eligible for eSBT. Equivalency of success rates, defined as no more than a 10% difference based on 95% confidence intervals (CIs), was compared between eSBT (n = 125) and eDBT (n = 213) groups. Results: Using traditional analysis techniques, no differences in pregnancy or live-birth rates were seen (eSBT: 84.6% vs. eDBT: 84.5%, P = 0.99; eSBT: 65.3% vs. eDBT: 72.3%, P = 0.23). The 95% CI around the difference in pregnancy rates ranged from -7.9 to 8.1, suggesting clinically equivalent pregnancy rates. Clinical equivalence was not established for live-births (95% CI = −18.5–4.5). Conclusions: Findings suggest comparable pregnancy rates can be achieved in a clinical setting when utilizing eSBT in good-prognosis patients. Although live-birth rate equivalence was not demonstrated, it is thought the additional complications associated with multiple gestations outweigh the potentially higher live-birth rate. The present study highlights the importance of utilizing equivalence analyses when making statements regarding the similarity of two treatments in reproductive health, rather than relying on superiority analyses alone.
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Luteinizing hormone receptor gene and regulator of G-protein signaling 2 gene expression level and association with oocyte maturity in in vitro fertilization/intracytoplasmic sperm injection cycle p. 52
Thanik Chokjirawat, Mutchuporn Sukpresert, Wicharn Choktanasiri, Wanwisa Waiyaput, Duangporn Saengwimol, Aruchalean Taweewongsounton, Tanjitti Pongrujikorn, Chonthicha Satirapod
DOI:10.4103/jhrs.JHRS_89_16  PMID:29681717
Aims: The aim is to study the relation and distribution in gene expression level of the luteinizing hormone receptor (LHR) gene and regulator of G-protein signaling 2 (RGS2) gene expression with oocyte maturation. Setting and Design: This cross-sectional study was undertaken in an instruction-based tertiary care infertility unit, department of obstetrics and gynecology. Materials and Methods: After controlled ovarian hyperstimulation, cumulus granulosa cells (CCs) from 59 oocytes among 18 women being treated by in vitro fertilization/intracytoplasmic sperm injection cycle technique from November 2015 to January 2016 were collected on the day of oocyte retrieval. Total RNA was extracted and converted to cDNA in individual oocytes. LHR and RGS2 gene levels were measured and analyzed using digital droplet polymerase chain reaction. Statistical Analysis: Gene expression level was analyzed using software STATA, version 14.0 (College Station, TX: StataCorp LP, USA). Results: CCs were obtained from 59 cumulus-oocyte complexes (COC), 46 COC from metaphase II (CCMII), 13 COC from metaphase I, and GV oocyte (CCMI + GV). The RGS2 gene expression level, when compared with the housekeeping gene in CCMIIand CCMI + GV, was 0.15 (0.05–0.52) and 0.08 (0.02–0.27), respectively. The LHR gene expression when compared with the housekeeping gene in CCMIIand CCMI + GVdid not differ and was quite in the same value that was 0.02 (0.00–0.11) and 0.02 (0.00–0.06), respectively. Conclusion: This study showed that LHR gene expression did not differ in between oocyte groups. Even though the median of RGS2 gene expression was more in the mature oocyte group, the result was inconclusive due to scattering and overlapping of gene expression data between oocyte groups.
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Therapeutic efficacy of endometrial scratching in repeated Controlled Ovarian Stimulation (COS) failure cycles p. 59
Leena Wadhwa, Mona Mishra
DOI:10.4103/jhrs.JHRS_130_17  PMID:29681718
Objective: The objective of the study was (1) “to evaluate the therapeutic efficacy of endometrial scratching in repeated controlled ovarian stimulation (COS) failure cycles.” And (2) “to compare differences in pregnancy outcome by endometrial scratching in early (D2–D4) and late follicular phases (D7–D9) of the same stimulation cycle.” Materials and Methods: Women attending infertility clinic in a tertiary care center and who have two or more repeated COS failure cycles and planned for COS with intrauterine insemination (IUI) were included in the study which is a prospective parallel, interventional, single-blinded, randomized control study, in 1:1 allocation ratio. A total of 165 patients were recruited and randomly allocated into three groups: Group A (n = 55) underwent endometrial scratching on D2–D4 of the same COS cycle, Group B (n = 55) on D7–D9, and Group C (n = 55) no intervention done. All the patients underwent COS according to standard protocol followed by IUI. Results: Clinical pregnancy rate was 12.73% (odds ratio [OR] =0.87 95% confidence interval [CI] =0.288–2.55, P = 1), 16.36% (OR = 1.15; 95% CI = 0.40–3.23, P = 1), and 14.54%, respectively, in Group A, B, and C, respectively (P = 0.86), as per intention to treat analysis. Using Chi-square test, P value between Group A and B was 0.787, between Group A and C was 1.000, and between Group B and C was 1.000. As per protocol analysis, clinical pregnancy rate was 13.46% (OR = 0.83; 95% CI = 0.27–2.5, P = 0.74), 19.57% (OR = 1.3 95%; CI = 0.45–3.73, P = 0.41), and 15.69%. Using Chi-square test, P value between Group A and B was 0.588, between Group A and C was 0.967, and between Group B and C was 0.815. No abortions and multiple pregnancies occurred in either of the groups. Conclusion: The effect found was of good quantum in Group B as per protocol analysis which could be of clinical relevance if larger sample size would have been taken. Endometrial scratching is a cost-effective and easy technique which may improve clinical pregnancy rates in previous COS failure cycles, but more trials are needed to be conducted using larger sample size to achieve the improved and significant outcome.
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CASE REPORTS Top

Intracytoplasmic sperm injection with assisted oocyte activation resulting in successful pregnancies and live birth in couples with globozoospermia: A report of two cases p. 72
Puneet Kaur Kochhar, Pranay Ghosh
DOI:10.4103/jhrs.JHRS_47_17  PMID:29681719
Globozoospermia, characterized by round-headed acrosomeless sperm, is a rare and severe form of teratozoospermia. We report a successful pregnancy in two cases of total globozoospermia after intracytoplasmic sperm injection (ICSI) with oocyte activation with calcium ionophore. In the first case, globozoospermia was diagnosed on the day of oocyte retrieval. Among 11 retrieved oocytes, only one fertilized after ICSI. The pregnancy test 2 weeks after embryo transfer was negative. Two months later, the patient underwent ovarian stimulation again. The 12 retrieved oocytes were exposed to calcium ionophore medium following ICSI. Four oocytes were fertilized and two blastocysts were transferred resulting in a clinical pregnancy. In the second case, among seven retrieved oocytes, three fertilized after ICSI and assisted oocyte activation, and two 8-cell embryos were transferred, resulting in a positive pregnancy. The successful outcome here justifies the use of ICSI with oocyte activation to improve the pregnancy rate significantly when dealing with globozoospermia.
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Live birth after rescue in vitro maturation–intracytoplasmic sperm injection in type 1 diabetes, polycystic ovary syndrome patient using clomiphene–antagonist protocol p. 75
Samundi Sankari, M Elanchezhian, Divya Selvamani, M Nagarajan, D Gopikrishnan
DOI:10.4103/jhrs.JHRS_65_17  PMID:29681720
Infertility in patients with polycystic ovary syndrome (PCOS) associated with diabetes leads to challenging situations seeking alternative treatments. In vitro maturation (IVM) followed by intracytoplasmic sperm injection (ICSI) could overcome the challenges with promising pregnancies in such patients. In the treatment of a 32-year-old diabetic woman who also had PCOS, single immature oocyte was retrieved. Rescue IVM followed by ICSI yielded a grade 1 day 3 embryo which on transferring resulted in pregnancy and a healthy infant was delivered. Rescue IVM–ICSI could help in achieving pregnancy and live birth. Stimulation involving clomiphene and gonadotropin-releasing hormone antagonist is an effective and patient-friendly protocol for women with PCOS and diabetes and also for poor responders.
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Progesterone hypersensitivity: A challenge for luteal support p. 79
Astha Gupta, Deepak Goenka, Mohan L Goenka
DOI:10.4103/jhrs.JHRS_116_17  PMID:29681721
Progesterone hypersensitivity is a rare phenomenon which can occur after both endogenous and exogenous exposures. We present a case of hypersensitivity to various forms and routes of exogenous progesterone. A 27-year-old female presented with primary infertility. Investigations revealed Grade 1 endometriosis and polycystic ovary syndrome. Three cycles of intrauterine insemination were attempted which were unsuccessful and in vitro fertilization was proceeded. Six blastocysts of Grade A were formed and cryopreserved. Artificial cycle was used for endometrial preparation for frozen embryo transfer (FET). However, due to failure to use exogenous progesterone due to hypersensitivity reaction, Modified Natural Cycle (MNC) was used. A follicle was formed using ovulation induction with tamoxifen and human menopausal gonadotropin. Ovulation was induced by human chorionic gonadotropin (hCG), and natural progesterone from corpus luteum was used. FET was done when endometrium was 8 mm. Pregnancy was confirmed by transvaginal ultrasound and β-hCG levels and continued uneventfully. Endogenous progesterone can be used as an alternative for endometrial preparation for FET in patients with exogenous progesterone hypersensitivity.
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