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   Table of Contents - Current issue
Coverpage
January-June 2022
Volume 9 | Issue 1
Page Nos. 1-73

Online since Wednesday, June 29, 2022

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EDITORIAL  

Editor view point - Ovarian hyper stimulation syndrome Highly accessed article p. 1
Kuldeep Jain
DOI:10.4103/fsr.fsr_12_22  
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Ovarian tissue cryopreservation– Where are we today? Highly accessed article p. 2
Rupali Goyal
DOI:10.4103/fsr.fsr_9_22  
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REVIEW ARTICLES Top

Prediction of ovarian hyperstimulation syndrome p. 5
Akanksha Sood, Raj Mathur
DOI:10.4103/fsr.fsr_45_21  
OHSS is best defined as an iatrogenic condition caused by inflammatory mediators released by the hyperstimulated ovaries. OHSS is associated with significant physical and psychosocial morbidity and has been associated with maternal death. However, in most cases OHSS is self-limiting and requires supportive management and monitoring while awaiting resolution. Because OHSS is the most serious consequence of controlled ovarian stimulation, every attempt should be made to identify patients who are at highest risk. If the “at risk” women can be identified prior to or during treatment, targeted preventive measures can be applied.
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Sperm DNA fragmentation and reproductive outcomes p. 10
Bindu Bajaj, Garima Kapoor
DOI:10.4103/fsr.fsr_49_21  
In the last few years, male infertility is increasingly catching the attention of researchers. The impact of spermatozoal factors on the fertilization and early embryo development is being deciphered. An association of sperm aneuploidy status in unexplained recurrent pregnancy loss has been observed. Sperm DNA damage or the sperm DNA fragmentation (sDF) is now measurable as DNA fragmentation index. The methods of evaluating sDF are many and they differ in their technique and paraphernalia needed to perform them. The most common methods are SCSA, TUNEL, SCD, COMET. TUNEL utilizes tagging of DNA in places where there is a break and then quantifying them. SCD is based on the principal of susceptibility of fragmented DNA to acid denaturation. COMET assay involves variable movement of intact and fragmented DNA under the influence of electric field. There are different methods to perform each of the previous mentioned tests though the principle remains the same. Each laboratory performing these tests needs to standardize them and should have their own cutoffs, which should relate to the procedure [intrauterine insemination/in vitro fertilization (IVF)/intracytoplasmic sperm injection] being performed. The role of sDF is slowly getting defined in recurrent implantation failures, unexplained infertility, varicocele, and IVF failures. Yet the jury is still out.
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Progestin primed ovarian stimulation protocol: current status in assisted reproductive technology p. 16
Rashmi Baid, Hrishikesh D Pai, Nandita P Palshetkar, Rishma D Pai
DOI:10.4103/fsr.fsr_48_21  
Progestin primed ovarian stimulation (PPOS) is a novel controlled ovarian stimulation protocol. Prevention of endogenous luteinizing hormone surge is an important step in assisted reproductive technology cycles. Gonadotropin-releasing hormone (GnRH) analogs are used conventionally for preventing premature ovulation before egg retrieval. However, GnRH analogs – both agonists and antagonists – have certain disadvantages such as increased cost, the requirement of daily injections, patient inconvenience, and adverse effects, which have prompted us to search for possible alternatives. Oral progesterone has been used recently as an effective alternative to GnRH analogs. Although the use of progestin requires mandatory cryopreservation of all the embryos due to embryo-endometrium asynchrony, advances in freezing techniques have rendered it feasible. Moreover, progestin is cost-effective, administered orally, convenient, and easily accessible. Hence, this new PPOS protocol combined with freeze-all cycles is an effective alternative to GnRH analogs for pituitary suppression during ovarian stimulation. This review aims to evaluate the current status of the PPOS protocol, its mechanism, different regimes, advantages, and disadvantages.
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ORIGINAL ARTICLES Top

Influence of sperm morphology in ICSI cycle outcomes: a retrospective study p. 23
Sazda Khatoon, Sonia Malik, Ved Prakash, Aneesha Grover
DOI:10.4103/fsr.fsr_17_21  
Aim: To determine whether sperm morphology has any influence on the assisted reproductive technique (ART) outcome in in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) cycles. Objectives: To assess whether sperm morphology affects IVF-ICSI outcome. Method: This study was a retrospective analysis of data from 1000 couples who had undergone ART cycle at Southend Fertility & IVF, Delhi between January 2016 and January 2021. The recruited patients were divided into two groups: Group A: Group A was the study group, and included 600 patients with an abnormal sperm morphology (morphology of <4%); Group B: Group B was the control group, and included 400 patients with a normal sperm morphology (morphology of >4%). The two groups were compared in terms of fertilization rate, embryo development rate, grade A embryo development rate, grade B embryo development rate, grade C embryo development rate, cleavage rate, embryo discarded or damage rate, and pregnancy rate. Results: Of the total 1000 ART-ICSI cycles analyzed the baseline characteristics, such as age, type of infertility, and semen parameters such as volume, count, motility, debris, agglutinations, grade A motility, grade B motility, total progressive (A+B) motility, morphology assessments, and type of protocol used for stimulation were comparable between the two groups. In the 1000 patients analyzed, a total of 6871 oocytes were injected at ICSI, of which 4049 oocytes belonged to group A and 2822 oocytes belonged to group B of the 6871 oocytes injected, 6275 got fertilized, giving a fertilization rate of 91.3%. On comparing the fertilization rate of the two groups, a fertilization rate of 90.1% (3650/4049) was observed in group A and 93.01% (2625/2822) was observed in group B, which was statistically different (P < 0.001). Of the various outcome parameters, a statistically significant difference was reported in the fertilization rate, cleavage rate, embryo development rate, grade A embryo development rate, and grade C embryo development rate in the two groups. No statistically significant difference was observed in the pregnancy rate. It was also observed that once fertilization occurred, embryo quality was good for all types of abnormal spermatozoa (grade A, good- to excellent-quality embryos), except for spermatozoa with broken necks, with which only good to excellent quality, or poor quality grade B and group C embryos were obtained. Conclusion: Sperm morphology influences the fertilization rate, cleavage rate, and the embryo development rate but there is no significant influence of sperm morphology on pregnancy rate.
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Sperm DNA fragmentation − can it be a routine? p. 29
Sasikala Natarajamani
DOI:10.4103/fsr.fsr_41_21  
Aim: To assess the correlation between semen parameters and sperm DNA fragmentation (SDF) and to examine whether SDF can be recommended as a routine test along with semen analysis. Materials and methods: Retrospective analysis was conducted for 118 male infertile patients attending a fertility clinic obtained from the records between 2017 and 2019. Semen analysis and SDF were assessed according to World Health Organization − 2010 guidelines and sperm chromatin dispersion test, respectively. Patients were grouped based on their SDF scores as “low DNA fragmentation group (LDF)” if SDF ≤ 18% and as “high DNA fragmentation group (HDF)” if SDF > 18%. Mann–Whitney and Kruskal–Wallis tests were used to find the difference in the mean of semen parameters between SDF groups. Statistical analysis was carried out using STATA Version-14. Results: The mean value of sperm concentration, motility, and normal morphology was higher in LDF compared to HDF. Correlation analysis showed patients’ age to be positively associated with SDF (r = 0.125; P = 0.102). Sperm concentration, progressive motility, and normal morphology had a weak negative correlation with SDF. Around 63% and 69% of patients with normal morphology and normal motility respectively had high SDF. In the HDF category, nearly 42% had normal morphology, whereas a 66% demonstrated normal motility. The results of Kruskal–Wallis test for patients who had a treatment outcome (conception) showed that patients in LDF group had 1.5 times higher chance of “conception and live birth.” Conclusion: Men with normal semen parameters can still have a high level of SDF. SDF along with semen analysis can help assess the reproductive potential of a male better.
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Retrospective analysis on the effect of duration of ejaculatory abstinence on fertilization, embryo development, and pregnancy rates in patients undergoing conventional in vitro fertilization p. 38
Sweta Gupta, Rahul Kumar Gupta, Sapna Yadav, Vikram Jeet Singh, Ajay Srivastava
DOI:10.4103/fsr.fsr_44_21  
Aim: This study aims to find out how different sexual abstinence period influences semen parameters, fertilization, embryo development, and pregnancy rates in patients undergoing conventional in vitro fertilization. Setting and designs: A retrospective analysis was conducted at a tertiary level infertility care clinic. Materials and methods: The clinical study included 532 patients between January 2017 and July 2021 who had been treated with conventional in vitro fertilization. The effect of sexual abstinence on primary outcomes such as semen volume, total sperm concentration, total motile sperm concentration, sperm morphology, and secondary outcomes such as fertilization rate, cleavage rate, top quality day 3 and day 5 embryo development rate, implantation and clinical pregnancy rate between fresh versus frozen embryo transfer on day 3 and day 5 of conventional in vitro fertilization under three groups, that is, sexual abstinence of less than or equal to 1, 2 to 5, and 6 to 7 days was evaluated. Statistical analysis used: Chi-square test was used to evaluate the qualitative variables whereas one-way analysis of variance was used to evaluate the quantitative variables. Results: Group II with 2 to 5 days of abstinence, observed a positive correlation between abstinence period and semen volume, total sperm concentration, total motile sperm concentration, and morphology. Fertilization rate was higher in groups II and III than group I (P = 0.21) with no significant difference in cleavage rate (P = 0.4) and embryo development on day 3 (P = 0.1057). The formation of AA grade blastocyst between group I and group II was 27.54 % and 23.47 %, respectively, with a P-value of 0.007154. Both fresh and frozen embryo transfers of groups II and III of abstinence period had implantation and clinical pregnancy rates of 23.39% and 43.83%, respectively. Conclusion: Our study did not find any significant difference in primary and secondary outcomes of conventional in vitro fertilization between the three groups. We recommend further prospective large randomized control studies to prove any association between duration of abstinence and pregnancy outcomes.
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Dual trigger increases the number of top quality embryos in normal responders p. 46
Priyanka Kalra, M Gouri Devi, Meeta Sharma
DOI:10.4103/fsr.fsr_1_22  
Context: Human chorionic gonadotropin (hCG) has been used for years for oocyte maturation in IVF cycles,however, with the risk of a few complications like ovarian hyperstimulation. The introduction of gonadotropin-releasing hormone (GnRH) agonist along with hCG as a dual trigger has helped to reduce the incidence of such complications. Aims: The study aims to compare the outcomes of IVF cycles in hCG versus hCG plus GnRH (dual trigger). Settings and Design: Retrospective center-based study. Materials and Methods: Retrospective center-based study to compare the effect of hCG and dual trigger on the cycle outcomes in normal responders. Statistics: Data analysis was done using ClinCalc online calculator through chi-square test, two-independent t test. P < 0.05 was considered to indicate statistical significance. Results: The number of oocytes and clinical pregnancy rates was higher in the dual trigger group. A higher number of top quality embryos were formed in the dual trigger group with statistical significance. Conclusions: Dual trigger can help to improve the outcomes of IVF in normal responders too.
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Impact of peak serum estradiol levels on the outcomes of hormone replacement therapy (HRT) frozen embryo transfer (FET) cycles p. 51
Priyanka Kalra, M. Gouri Devi, Meeta Sharma
DOI:10.4103/fsr.fsr_5_22  
With the improvised ovulation induction methods coming up, FET (Frozen Embryo Transfer) has gained preference over fresh transfers. Several strategies have been devised for preparing the endometrium for FET, out of which the hormone replacement regimen (HRT) with exogenous estrogen and progesterone supplementation still remains the most popular one. There are different clinical protocols for the transfer of frozen-thawed embryos. However, there has always been a debate about the impact of hyperestrogenism on endometrial development and implantation, particularly when controlled ovarian hyperstimulation is used in conjunction with fresh embryo transfers. We conducted this study with an objective to investigate the impact of variable serum estradiol (E2) levels achieved in the late follicular phase on implantation and pregnancy outcomes of cryopreserved/thawed embryos transferred in programmed cycles with exogenous hormonal replacement.
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Dose vitamin D supplementation affect reproductive outcomes in patients with polycystic ovary syndrome? p. 55
Ramy M Elnaggar, Ahmed S Soliman, Ayman S Dawood
DOI:10.4103/fsr.fsr_6_22  
Objective: To evaluate the effect of vitamin D supplementation on ovulation and pregnancy rates in patients with polycystic ovary syndrome (PCOS). Material and Methods: This multicenter randomized controlled clinical trial was performed in the infertility clinics of Tanta University Hospital and Benha University Hospital. One hundred and sixty patients were recruited and allocated into two groups; group 1 served as a control group and group 2 (study group) where patient received vitamin D supplementation. Induction of ovulation with clomiphene citrate. Results: No significant differences were seen in in demographic data: basal hormonal levels, mature follicle size, serum progesterone levels, or pregnancy rate between both groups. Insulin resistance was greater in the control group and resumption of the cycle was higher in the study group. Conclusion: Vitamin D supplementation as an adjuvant to induction of ovulation in women with PCOS resulted in enhancement of ovulation and pregnancy rates.
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Medical management of ectopic pregnancy with two different regimens of methotrexate: A comparative study p. 61
Poonam Laul, Rubi Gupta, Vidushi Saxena, Pinkee Saxena
DOI:10.4103/fsr.fsr_7_22  
Background: The timely and early diagnosis of ectopic pregnancy has made medical management of ectopic pregnancy the preferred treatment. Methotrexate is used in various regimens to treat ectopic pregnancy. A study was carried out to compare the effectiveness of double-dose and single-dose methotrexate regimen in medical management of unruptured ectopic pregnancy. Materials and Methods: The study included 80 hemodynamically stable patients with unruptured ectopic pregnancy. They were then randomly assigned in to two groups. Group A patients received two doses of methotrexate 50 mg/m2 on day 1 and day 4 whereas group B patients received single dose 50 mg/m2 methotrexate on the day 1. Serum β human chorionic gonadotropin (β-hCG) and blood parameters were measured in both the groups on day 4 and day 7 followed by serial serum β-hCG weekly till negative value was obtained. Outcome measures were success rate of treatment, need for extra dose of methotrexate, need of laparotomy, and side effects of methotrexate. Results: The two groups were comparable in demographic parameters, baseline serum β-hCG, and blood parameters. The treatment success rate was slightly more in group A (70%) than group B (65%); however, it was statistically insignificant. Need of extra dose of methotrexate was 5% in group A and 17.5% in group B, respectively. Ten patients in group A and seven patients in group B underwent laparotomy for rupture of the ectopic mass. The reported side effects of methotrexate was comparable in both the groups. Conclusion: Study shows that double-dose methotrexate is as effective as single dose in the medical management of ectopic pregnancy. It has slightly better success rate though statistically insignificant, with less need for extra dose and less duration of follow-up.
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CASE REPORTS Top

A rare case of bowel obstruction and intraperitoneal adhesions following uterine artery embolization p. 66
Akanksha Sood, Wal Baraza, Nikolaos Tsampras
DOI:10.4103/fsr.fsr_2_22  
Uterine artery embolization (UAE) is considered a safe and effective alternative to surgery for the treatment of fibroids. Vaginal discharge, hematoma, fever, postembolization syndrome, fibroid expulsion, and failure are commonly reported complications, while severe vascular complications are rare. Retrospective studies including patients having hysterectomy after UAE indicated the increased prevalence of intra-abdominal adhesions. We are presenting a rare case of severe intra-abdominal adhesions causing bowel obstruction, in need of emergency laparotomy, following UAE.
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Successful pregnancy in recurrent thin endometrium: a case report p. 68
Madhuprita Agrawal, Suresh K Agrawal, RB Agrawal, Akash Agrawal, Shweta Agrawal
DOI:10.4103/fsr.fsr_3_22  
Human endometrium plays an important role in the implantation process. Endometrial thickness is considered to be one of the valuable parameters contributing to the successful outcome of the assisted reproductive technique. Young patients less than 35 years have a better chance of conceiving even if they have thin endometrium. It is suggested that a frozen cycle instead of fresh transfer allows for a better and more detailed study of the endometrium. Many modalities have been applied to improve endometrial thickness but their effectiveness remains controversial. Here we present a 30-year-old female trying for conception for 8 years and has a history of four times recurrent IVF failure. On ultrasonography, the endometrium lining was always in the range of 5 to 6.5 mm. Frozen embryo transfer (FET) was done with mild-ovarian stimulation (OS) protocol, the dominant follicle was tracked, and trigger given and was followed by three blastocyst transfers. The patient came positive with a twin pregnancy. Endometrium potential cannot be judged only based on thickness, other parameters like endometrial blood flow and its pattern equally should be considered. Although hormone replacement therapy and NC (natural cycle)/modified NC are the most commonly used protocols, the present case suggests that mild OS may be an emerging and viable option for FET.
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Spontaneous conception during in vitro fertilization prior to embryo transfer during the COVID-19 lockdown p. 71
Swati Kumari
DOI:10.4103/fsr.fsr_4_22  
Intercourse during IVF treatment traditionally had been discouraged for the purpose of avoiding trauma to the hyperstimulated ovaries, optimizing semen parameters, and preventing multifetal conception and ovarian hyperstimulation syndrome. The probability of spontaneous conception during an IVF cycle is minimal; however, a few cases have been reported in the literature. Recently, there was a case of unexplained infertility with no conception for 12 years and she conceived spontaneously post ovum pickup prior to embryo transfer. Previously she underwent six cycles of follicular monitoring timed intercourse and six cycles of IUI. Given the infrequent prevalence of such an occurrence, we aim to present and discuss this case.
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