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   Table of Contents - Current issue
July-December 2017
Volume 4 | Issue 2
Page Nos. 69-125

Online since Friday, August 3, 2018

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Editor’s view point p. 69
Kuldeep Jain
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Stem cells—The new agents in infertility treatment: The light at the end of the tunnel? Highly accessed article p. 70
Gita Radhakrishnan
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Ovarian reserve p. 74
Pinkee Saxena, Surveen Ghumman, Shashi Prateek
Nowadays more and more couples are delaying childbirth. As the age of the couples advances, their chances of achieving pregnancy decrease. This is due to the natural process of ageing of gonads. During counselling and treatment of infertile couples, clinicians are often faced with questions like what is the chance of conception. Hence there is need to test for functional ovarian reserve. An ideal ovarian reserve test is affordable, convenient, reproducible and sensitive. Various clinical and biochemical markers have been used to predict the same. These tests help to predict the poor response or hyper response to ovarian stimulation and help to formulate the treatment plans in infertile couple. They however cannot predict future fertility or occurrence of pregnancy.
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A comparison of microdose flare versus antagonist protocol in poor responders chosen according to the Bologna criteria p. 81
Neena Malhotra, Latika Chawla, Reeta Mahey, Anupama Bahadur, Ashok K Bhatt, Alka Kriplani
Background: Uncertainty exists in deciding the optimal stimulation protocol in poor responders undergoing in-vitro fertilization (IVF). Our study aims to compare microdose flare and antagonist protocols in the management of patients considered to be poor responders, chosen according to Bologna criteria. Materials and Methods: In a prospective observational study, 66 poor responders as per the Bologna criteria were recruited to undergo IVF-ICSI cycles using either microdose flare protocol (Group I; n = 28) or the flexible antagonist (Group II; n = 38). Pregnancy rate per cycle was taken as the primary outcome. Total days of stimulation, total dose of gonadotropins, estradiol (E2) and progesterone levels on the day of human chorionic gonadotropin (hCG) trigger, cycle cancellation rate, total oocytes retrieved, total Metaphase II (MII) oocytes, number of embryos formed, number of Grade I embryos, fertilization and cleavage failure, total number of cycles that did not reach embryo transfer were taken as secondary outcome measures. Results: There was no significant difference in the pregnancy rates between the two groups. The microdose flare group (Group I) had higher levels of E2 on the day of hCG trigger (P = 0.03) and more number of MII oocytes (P = 0.04). Conclusion: Patients stimulated with the microdose flare protocol had significantly more E2 levels with the recovery of more MII oocytes, but this did not transform to higher pregnancy rates. A large multicentered randomized trial would be required to draw definite conclusion to achieve significant difference between the cycle cancellation and pregnancy rates between these two protocols for poor responders.
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Retrospective analysis of GnRH antagonist cycles to assess ovarian reserve parameters as the predictors of clinical pregnancy p. 87
Surveen Ghumman, Shipra Gupta, Sandesh Patel
Aim: The present study aims to correlate AMH and AFC, with the number of retrieved oocytes , number of Grade1 embryos and clinical pregnancy in IVF/ICSI cycles stimulated with GnRH-antagonist protocol. Materials and Methods: 49 women who underwent grade 1 cleavage stage fresh embryo transfer from May to August 2017 were included. Primary end point was clinical pregnancy i.e. positive cardiac activity at 6 weeks. Pearson’s correlation coefficient was calculated and stepwise regression analysis was done to identify the best predictor. Results: Out of 49 patients 21 patients (42.9%) were pregnant. Serum AMH and AFC significantly correlated with the number of oocytes obtained (P=0.00, P=0.00). A positive correlation of serum AMH and AFC was seen with number of grade 1 embryos , but it was not significant. AFC had a stronger correlation with number of oocytes and grade 1 embryos than AMH . Stepwise regression analysis indicated that number of grade 1 embryos was an independent predictor for clinical pregnancy (P= 0.19) with an overall accuracy of 63%. Conclusion: Counselling of patients regarding outcome of IVF cycle should be based on the number of grade1 embryos.
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Ovarian interleukin profile and pregnancy outcome in women undergoing assisted reproduction: A prospective study p. 93
Yogesh Kumar, Saumya Prasad, Mohammad A Khan, Syed A Husain, Sudha Prasad, Shashi Sharma
Context: Ovarian interleukins (ILs) mediate folliculogenesis, gametogenesis, fertilization, embryo development and implantation. Aims: Evaluation of the role of the quantitative levels of follicular fluid (FF) IL-1Beta (1β), IL-10 and IL-12B (p-40 subunit) in women underwent assisted reproduction. Setting and Design: Prospective observational study conducted between July 2013 and August 2015 at University Hospital’s in vitro fertilization (IVF) set up in North India. Materials and Methods: Women (n = 168) were worked up for IVF/intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles. FF samples were pooled and collected from ovarian follicles of size ≥16 mm for each woman on the day of oocyte retrieval. Quantitative levels of IL-1β, IL-10 and IL-12B were estimated by enzyme-linked immunosorbent assay technique. Quantitative levels along with demography, cycle characteristics, endometrial thickness, number of retrieved oocytes, fertilization rate and embryos quality were compared between pregnant and nonpregnant groups of women. Student T-test, Mann–Whitney U-test, chi-squares test and logistic regression were applied as appropriate. Statistical significance level was calculated at P < 0.05. Results: Women (n = 168) were divided into pregnant (Group A; n = 75) and nonpregnant (Group B; n = 93) groups. The median levels of IL-1β, IL-10 and IL-12B levels were found significantly lower in women in Group A as compared to Group B [41.2 pg/mL (1.7–370) vs. 78.5 (5.6–313.58); P < 0.001**, 53.2 pg/mL (1.8–183.7) vs. 135.2 pg/mL (1.3–385.4); P < 0.001** and 115.3 pg/mL (3.8–822.9) vs. 178.3 pg/mL (36.1–1938.3); P < 0.009*, respectively]. Conclusion: Lower concentrations of IL-1β, IL-10 and IL-12B in FF were found in a protagonist with positive pregnancy outcome and can be served as a reliable predictive marker of successful IVF/ICSI-ET outcome in women underwent assisted reproduction.
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Comparison of fresh versus frozen embryo transfer in women with polycystic ovary syndrome p. 102
Kanad Dev Nayar, Rhythm A Gupta, Monica Gupta, Minal Singh, Gaurav Kant, Divya Nayar
Introduction: Transfer of fresh embryos is a usual practice but in women at risk of ovarian hyperstimulation due to excess follicle development, elective cryopreservation of all embryos followed by transfer in subsequent cycle is preferred. Fresh cycles have supraphysiological steroid levels which may alter the endometrial receptivity and probably affect placentation adversely whereas frozen embryo transfer is performed to the uterus after a programmed physiologic cycle of hormone replacement to prepare the endometrium. Objective: To find out whether frozen embryo transfer in subsequent cycle is better than that in fresh transfer in women with polycystic ovary syndrome (PCOS) when human chorionic gonadotropin (hCG) is used as a trigger in antagonist cycles. Study Design, Size, Duration: It is a prospective cohort study. Infertile women <35 years with the PCOS diagnosed by Rotterdam criteria who were undergoing their first in vitroPlease check whether the suggested full form for the acronyms in vitro fertilization (IVF) and assisted reproductive techniques (ART) provided in the article is correct. fertilization cycle from 1st January 2015 to 28th February 2016 were included. Cycles complicated by ovarian hyperstimulation syndrome were excluded. Participants/Materials, Setting, Methods: Women (N = 126) with terminal estradiol levels below 2500 pg/ml were triggered with recombinant hCG, and based on the number of retrieved oocytes, they were divided into two groups: Group A <15 oocytes retrieved had fresh embryo transfer on day 3 and Group B where >15 oocytes were retrieved, but all embryos were frozen on day 3 and transferred in subsequent cycle. Primary outcomes were clinical pregnancy rates and live birth rates. Secondary outcomes were fertilization, implantation and miscarriage rates. Results: Group A had 73 fresh transfer, and Group B had 53 frozen embryo transfer. Both groups were comparable regarding age, body mass index, basal follicular stimulating hormone, antimullerian hormone and antral follicle count. Categorical data were represented as frequency and percentages, differences in these measures between the groups were compared using chi-square tests, and quantitative data were analyzed by using student t test. Clinical pregnancy rates (Group A: 38.4% versus Group B: 41.5%, P = 0.88) and live birth rate (Group A: 26.0% versus Group B: 33.9%, P = 0.25) were slightly higher in Group B though not statistically significant. The miscarriage rate in both the groups was comparable (Group A: 15.1% and Group B: 15.1%, P = 0.8).
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Single versus double intrauterine insemination—in artificial insemination donor stimulated cycles—impact on the clinical pregnancy rate: A randomized trial p. 106
Vinu Choudhary, Manisha Choudhary, Usha Shekhawat
Introduction: Male factor infertility affects almost 30–50% of infertile couples worldwide. The use of donor sperm intrauterine insemination (IUI) is an option for couples with absolute azoospermia, severe male factor infertility, sexual dysfunction and unaffordability for in-vitro fertilization. The data on the utility of double IUI using donor sperm are limited due to the lack of randomized controlled trial’s and conflicting conclusions. The objective of this study was to evaluate the utility of frozen double donor sperm IUI to improve clinical pregnancy rate. Materials and Methods: A total of 200 participants that fulfilled the inclusion criteria were enrolled for the study following randomization after preliminary work up. Random distribution was made using sequentially numbered envelope method in both groups (single and double IUI). Results: In this dataset comparing single and double donor sperm IUI, there was no significant difference in clinical pregnancy rates. The clinical pregnancy of 11 participants (11%) (out of 100 participants) in single IUI group and 13 participants (13%) (out of 100 participants) in double IUI group was seen. Conclusion: However, clinical pregnancy rate was statistically significant with gonadotrophins in double IUI group in our study.
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Correlation of basal serum anti-Mullerian hormone level with oocyte quality and embryo development potential in women undergoing IVF-ICSI p. 112
Sweta Gupta, NarendraBabu Karuputhula, Nancy Kumar, Ajay Srivastava, Bikramjit Singh, Kamta Dubey
Objectives: To assess and correlate the oocyte morphological characteristics and embryo development in women with normal serum anti-Mullerian hormone (AMH) levels for different age groups women undergoing in vitro fertilisation (IVF). Materials and Methods: It is a retrospective study. A total of 92 women undergoing IVF treatment with normal AMH levels within two different age groups were included in the study based on retrospectively collected data from medical records. Based on age, women were subdivided into two groups: Group A with age >23 to <30 years (n = 40) and Group B with age >30 to <38 years (n = 52). The oocyte morphological characteristics were assessed and scored based on previously published method with minor modifications. Oocytes and embryo development were correlated in both groups with different age women (>23 to <30) Group A and (>30 to <38) Group B. Results: Patients’ demographic characteristics did not show significant difference in Groups A and B, except age (P < 0.05). Number of oocyte retrieved, number of mature MII oocytes and fertilization rate have not changed in both the groups. Good quality embryo development significantly improved in Group A than that in B (P < 0.05). Even mature oocyte number in both the groups was not statistically significant. However, oocyte morphological characteristics such as (1) oocyte overall morphology, (2) zona pellucida color and thickness, (3) size of perivitelline space (PVS), (4) presence of granules and (5) morphology of polar body and pattern of cytoplasm were significantly affected in Group B older age group women when compared with younger group women (Group A). Conclusion: AMH seems to be a better predictor of quality of oocytes and subsequently embryo development in older age group women when compared to the younger group women. Normal AMH level is a better predictor for ovarian reserve and along with this, it may help to predict oocyte quality and embryo development in older women undergoing IVF. Statistical Analysis: A student t test was applied to compare the means of two groups by online GraphPad software (www.graphpad.com/quickcalcs/, GraphPad Software, La Jolla, CA, USA). A P < 0.05 was considered statistically significant. Ethics: This is a retrospective study, and informed, signed consent was obtained from every couple prior to IVF treatment. Further, permission to use their data for analysis with guarantees of confidentiality was obtained. This study was exempted of institutional review board approval, since it involved only the analysis of medical records from established clinical practices.
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A prospective study to assess the mental health and quality of life in women undergoing assisted reproduction p. 117
Sudha Prasad, Yogesh Kumar, Poonam Nayar, Saumya Prasad, Garima Sharma
Context: Infertile women may experience high levels of psychological distress. The assessment of stress levels specifically related to infertility and the quality of life during infertility management needs to be evaluated. Aims: To study the psychological health of women undergoing assisted reproduction. Settings and Design: A cross-sectional study conducted between March 2014 and April 2015 at a tertiary care in-vitro fertilization setup in India. Subjects and Methods: Clinical interview and self-report measures were applied for an assessment of the psychological state of infertile women (N = 186). Anxiety was evaluated by Hamilton’s Rating Scale and Sinha’s Comprehensive Anxiety Test. Depression was assessed using Hamilton’s Rating Scale, Amritsar Depressive Inventory. Fertility and Quality of Life Questionnaire (FertiQoL) was applied to measure infertility specific stress. Overall life stress, covering all areas of life, was assessed using Presumptive Stressful Life Events Scale. Cornell Medical Index was applied to evaluate overall physical and mental health. Statistical Analysis: Student’s t-test and chi-square test were applied, and statistical significant levels were calculated at P < 0.05. Results: Clinically, significant depression was identified in 60.11–64.86% of the women. However, relatively lesser frequency of anxiety (27–37%) was observed. FertiQoL scores suggest that infertility treatment in itself is stressful, and nearly 80% of women reported increased levels of general life stresses. Conclusion: Being infertile has profound detrimental psychological impact on the life of women. Women undergoing treatment had significant high levels of psychological stress, depression and anxiety along with a lowered quality of life.
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