The Journal of Obstetrics and Gynaecology of India
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VOL. 73 NUMBER 4 July-August 2023 Regular Issue

Enzyme-Disrupting Chemicals as the Elephant in the Room for Infertility

Geetha Balsarkar1


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In Contemporary Reproductive Medicine Human Beings are Not Yet Dispensable

Gautam N. Allahbadia1,2 · Swati G. Allahbadia2 · Akanksha Gupta3

In the past few years almost every aspect of an IVF cycle has been investigated, including research on sperm, color doppler in follicular studies, prediction of embryo cleavage, prediction of blastocyst formation, scoring blastocyst quality, prediction of euploid blastocysts and live birth from blastocysts, improving the embryo selection process, and for developing deep machine learning (ML) algorithms for optimal IVF stimulation protocols. Also, artificial intelligence (AI)-based methods have been implemented for some clinical aspects of IVF, such as assessing patient reproductive potential and individualizing gonadotropin stimulation protocols. As AI has the inherent capacity to analyze "Big" data, the goal will be to apply AI tools to the analysis of all embryological, clinical, and genetic data to provide patient-tailored individualized treatments. Human skillsets including hand eye coordination to perform an embryo transfer is probably the only step of IVF that is outside the realm of AI & ML today. Embryo transfer success is presently human skill dependent and deep machine learning may one day intrude into this sacred space with the advent of programed humanoid robots. Embryo transfer is arguably the rate limiting step in the sequential events that complete an IVF cycle. Many variables play a role in the success of embryo transfer, including catheter type, atraumatic technique, and the use of sonography guidance before and during the procedure of embryo transfer. In contemporary Reproductive Medicine human beings are not yet dispensable.

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Voices from Health Care Providers: Assessing the Impact of the Indian Assisted Reproductive Technology (Regulation) Act, 2021 on the Practice of IVF in India

Jaydeep Tank1 · Prabha Kotiswaran2 · Parikshit Tank1 · Dev Tank3 · Jash Tank4

The regulatory vacuum in the field of ART in India was filled when in December 2021, the Assisted Reproductive Technology (Regulation) Act, 2021 (ART Act) (https:// egaze tte. nic. in/ Write ReadD ata/ 2021/ 232025. pdf) and the Surrogacy (Regulation) Act, 2021 (SR Act) were passed. We surveyed medical professionals to understand their knowledge, attitude and perception towards the Acts and to offer an initial, snapshot assessment of their impact on the medical community. The government has already signalled its intent to implement the Acts and has published several notifications/gazettes to clarify and amend the issues surrounding the Acts (https:// artsu rroga cy. gov. in/ Natio nalAr tSurr ogacy/ faces/ HomeP age. xhtml#). We hope that these responses will help to voice the thoughts, concerns and suggestions from of ART service providers for ART to further clarify and rationalise the laws. Infertility is already a much stigmatised problem which deserves to be a higher public health priority. While the laws are a welcome step, changes in both laws is are the need of the hour to make ART more accessible, available and affordable to the millions of couples who need these services and for the health care providers who to be able to deliver them.

ART Act · ART · Survey · Donors · IVF · Doctors · Surrogacy · Gametes
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OBSTETRICS

Pregnancies in Elderly Mothers over 40 years: What to Expect from the Rising New Age High‑Risk Cohort?

Sunil E. Tambvekar1 · Shilpa Adki2 · Nozer K. Sheriar3

Introduction Elderly women are believed to experience many risks associated with pregnancy. Literature fails to provide a clear consensus on the age group in which there is a rise in risk and pathophysiology contributing. ‘Pregnancies over forty’ are increasing in society, owing to changing lifestyles and sensibilities of youth and the advent of assisted reproductive techniques. In India, studies on elderly pregnant women above 40 years of age are lacking. The aim of this study is to assess these pregnancies, their course, obstetric and perinatal outcomes in women delivering above 40 years.

Methods The study group (Group A) comprised of pregnancies in 50 women at age ≥ 40 years on the date of delivery. The control group (Group B) had 50 women who delivered subsequent to the study group and age < 40. Various parameters and outcomes including parity, gestational age, number of gestations, co-existing medical illnesses, the incidence of hypertensive diseases of pregnancy (HDP), gestational diabetes mellitus (GDM), pre-term labor, mode of delivery, birth weight and obstetric and neonatal outcomes were compared. Chi-square test and independent T test were used for statistical analysis.

Results While a good number of patients conceived spontaneously and with basic infertility management, i.e., 84% in the elderly gravid group (Group A) and 96% in the control group (Group B), the number of patients who required ART in Group A were statistically significant (Group A 16% and Group B 4%). Incidence of pre-existing medical diseases like hypertension, diabetes mellitus, thyroid dysfunction, other auto-immune diseases and chronic diseases were noted to be high (26%) in Group A (statistically significant difference). Incidence of HDP, GDM and fetal growth restriction were high in Group A. Tendency to have the presence of fibroid uterus was high in patients in Group A, i.e., 24%, compared to only 8% in the control group; difference was statistically significant. Proportion of pre-term deliveries were high in Group A. Cesarean section rate was high in Group A, though it was not statistically significant. Other perinatal observations and neonatal outcomes were comparable in both groups; differences were not statistically significant.

Conclusion The study reveals an association of a high-risk course of pregnancies in women above the age of 40 years. Proportions of IVF pregnancies are higher in elderly women. Interestingly, the proportion of women in elderly group who conceived spontaneously and with basic infertility management including IUI was 84% in the present study. Medical comorbidities and incidence of fibroids were high in elderly women. Obstetric and neonatal outcomes of these pregnancies when managed efficiently are favorable.

Advanced maternal age · Pregnancy above 40 years of age · High-risk pregnancy
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GYNECOLOGY

Impact of Ovarian Factor Mediums on the Apoptotic Gene Expression and Embryo Quality Derived From Vitrified Immature Human Oocytes

Hakimeh Akbari1 · Hossein Foruozandeh1 · Masoud Mohammadi1

Background Condition mediums have a potential role in oocyte development. In this study, we evaluated the effects of different mediums on the developmental potential of vitrified immature human oocyte after IVM and parthenogenesis by ionomycin.

Methods Immature oocytes were collected from 184 women after vitrification/thawing and maturation, in three types of IVM mediums separately. Finally, 151 IVM MΙΙ oocytes were obtained and randomly divided into six groups and underwent the following intervention. Fresh and vitrified-thawing MΙΙ oocytes were activated after IVM in three conditioned mediums by ionomycin. Mediums included 1) Minimum Essential Medium Alpha (α-MEM) (as control medium), 2) α-MEM supplemented with supernatants of Mesenchyme bone marrow (B.M), 3) α-MEM with ovarian growth factors (O.F). Then, scoring of parthenote embryos was undertaken in accordance with pertinent morphological properties. Moreover, the expression of Bax and Bcl2 were determined in the parthenote embryos.

Result Percentage of the degenerated oocyte, 2–4 cells, 4–8 cells, and 16 cells, was different in the experimental groups. Also, cytoplasmic maturation and blastocyst formation rates were significantly different (p < 0.05) between the control and the other mediums. The highest mRNA expression levels of Bcl2 and Bax genes in parthenotes were observed in the fIVM O.F and vIVM α-MEM mediums, respectively. vIVM, α-MEM and fIVM O.F showed the lowest expression of Bcl2 and Bax genes, respectively.

Conclusion Our findings indicate that the O.F. medium had more potent effects on oocyte growth and cytoplasmic maturation up to the blastocyst stage with the highest expression level of the BCL2 gene and the lowest relative amount of the BAX gene in this medium. The results of the present study have been verified only for parthenogenetically activated embryos, and any positive effect of the environment on the egg/embryo fertilized with sperm requires more extensive studies.

IVM · Conditioned medium · Parthenogenesis · Developmental potential · Oocyte activation
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GYNECOLOGY

The effect of zinc supplementation on improving sperm parameters in infertile diabetic men

Hakimeh Akbari1 · Leila Elyasi2 · Ali Asghar Khaleghi1 · Masoud Mohammadi1

Background and aims Diabetes mellitus (DM) may have different adverse effects on the male reproductive system. Zinc (Zn) is one of the necessary elements in the human and mammalian diet that plays an important role in scavenging reactive oxygen species (ROS) by providing antioxidant and anti-apoptotic properties. The aim of this study was to determine the protective effects of zinc supplements on sperm chromatin and the evaluation of sperm deoxyribonucleic acid (DNA) integrity in diabetic men.

Methods In this interventional study, 43 infertile Iranian men in diabetic and non-diabetic groups were included. They were then randomly divided into two subgroups: normal saline intake and zinc sulfate intake (25 mg orally for 64 days each). Different indices of sperm analysis (number, morphology and motility) and testosterone levels were evaluated in four groups. Protamine deficiency and DNA fragmentation were assessed using chromomycin A3 (CMA3) and sperm chromatin dispersion (SCD) methods, respectively.

Results Zinc supplementation reduced the deformity of neck and head of sperms (p < 0.05), as well as deformity of sperm tail in infertile diabetic men. Zinc administration ameliorated sperm motility types A, B and C (p < 0.05). Moreover, zinc administration reduced abnormal morphology and DNA fragmentation of sperms, which increased the SCD1 and SCD2 and reduced the SCD3 and SCD4 in both treated groups.

Conclusion Zinc supplementation, as a powerful complement, is able to balance the effect of diabetes on sperm parameters, sperm chromatin and DNA integrity. Consequently, zinc supplementation can probably be considered a supportive compound in the diet of diabetic infertile men.

Sperm · Infertile · Male · Semen · Zinc
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GYNECOLOGY

Effects of Non‑Cavity‑Distorting Intramural Fibroids on IVF Outcomes in Patients with Recurrent IVF Failure: Does Myomectomy Change IVF Outcomes ?

Ugur Deger1 · Ekin Altinbas2 · Melis Karabay2 · Yagmur Karatas2 · Zeynep Deniz2 · Ceyda Buyuker2 · Sule Yildirim Kopuk3 · Bulent Tiras2,3 · Yigit Cakiroglu2,3

Background Uterine fibroids are the most common benign smooth muscle tumors of the uterus. However, there is no consensus on whether myomectomy improves IVF success in women with non-cavity-distorting intramural fibroids. The aim of this study was to compare the IVF and pregnancy outcomes of women who had non-cavity-distorting intramural fibroids and underwent myomectomy vs women who had intramural fibroids, but did not undergo myomectomy.

Methods A retrospective cohort study at Acibadem Maslak Hospital, IVF Center, between 2019 and 2020. Data of 128 women aged between 25 and 43 years who have at least 2 intramural non-cavity-distorting fibroids of 2–6 cm in size were used. All patients had at least two IVF failure. The intervention group comprised women who decided to proceed to myomectomy before IVF (Group 1, n = 56). The control group was established women with intramural fibroids who reject myomectomy (Group 2, n = 71).

Results In regard to IVF result parameters and perinatal outcomes, there was no statistically significant difference between the two groups. Between study groups, there were no statistically significant differences in the perinatal outcomes. Myomectomy surgery did not increase miscarriage and biochemical pregnancy rate (odds ratio (OR) 0.9; 95% confidence interval (CI) 2.8–3.7). Conclusion Myomectomy does not impact on pregnancy or live birth rates substantially, according to the results of this study.

Intramural fibroids · Non-cavity-distorting · In vitro fertilization · Myomectomy · Perinatal outcome
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GYNECOLOGY

Elective Single Cleavage‑Stage Embryo Transfer in IVF Patients with Suboptimal Ovarian Response is Not Detrimental to Cumulative Pregnancy and Reduces Multiple Pregnancy Rates.

Alessio Paffoni1 · Sabrina Cesana1 · Laura Corti1 · Hilda Wyssling1 · Alessandro Kunderfranco1 · Marco Claudio Bianchi1

Purpose To evaluate whether elective single embryo transfer in patients with suboptimal response to ovarian stimulation is
detrimental to pregnancy rates compared to double embryo transfer.
Methods A case–control retrospective study was performed in a cohort of couples undergoing IVF at the Infertility Unit of
the ASST Lariana with ≤ 9 oocytes and at least 2 viable embryos. A total of 424 women were analyzed in the “double embryo
transfer” group (n = 212) and elective “single embryo transfer” group (n = 212); they were matched 1:1 for female age, ovarian
reserve and number of previous cycles. Cumulative clinical pregnancy rate per oocyte retrieval was the main outcome.
Results The cumulative pregnancy rate per cycle, including the fresh embryo and subsequent frozen embryo transfers, was
26% and 26%, respectively. Considering the main confounding factors, a binomial logistic model indicated that the cumulative
clinical pregnancy rate was not significantly affected when a single embryo transfer was performed in women recovering
up to nine oocytes.
Conclusion Live birth rate was similar between the two groups, while twin pregnancies were significantly reduced in women
receiving single embryo transfer suggesting that elective single embryo transfer in patients with a limited number of embryos
is not detrimental to pregnancy rates.

Poor ovarian response · Single embryo transfer · In vitro fertilization · Twin pregnancy
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GYNECOLOGY

Aspiration with Diosmin Intake in Endometrial Cavity Fluid Accumulation in ART Cycles: A Randomized Controlled Trial

Ahmed Samy Saad1 · Khalid Abd Aziz Mohamed1

Background This was a prospective randomized controlled trial in 200 cases presented with endometrial cavity fluid at the day of oocyte retrieval at a private fertility center from 2013 to 2021. The cases were randomized at day of ovum pickup into 2 groups: Group 1 (control group) (n = 100): conventional management with follow-up and reassessment by transvaginal ultrasound on day 5. Group 2 (interventional group) (n = 100): aspiration of the fluid was done and cases were given diosmin 500 mg 3 times per day till reassessment at embryo transfer day. In both groups, we proceeded with fresh embryo transfer if no fluid is present on day 5 or freeze-all policy if persistent fluid was detected.

Results Endometrial fluid on the 5th day was significantly higher in the control group (28.0%) than in the interventional group (6.0%) (P < 0.001). Regarding pregnancy rate, although being higher in the interventional group (54.3% vs 50.0%), the difference was not statistically significant (P = 0.5). It was found that the intervention was associated with risk reduction of endometrial fluid (OR = 0.168, 95% CI = 0.065–0.429, P < 0.001.

Conclusion Aspiration of endometrial cavity fluid with diosmin intake increased the likelihood of fresh embryo transfer and with a slightly better pregnancy rate compared to conservative management. Clinical trial number: NCT02158000, Date of registration: 6/6/2014, Date of initial enrollment (first patient recruiting): 1/11/2014, URL: https:// clini caltr ials. gov/ ct2/ show/ NCT02 158000.

Endometrial fluid · Diosmin · Complications of ART cycles
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GYNECOLOGY

Deep Inception‑ResNet: A Novel Approach for Personalized Prediction of Cumulative Pregnancy Outcomes in Vitro Fertilization Treatment (IVF)

Gaurav Majumdar2 · Abhishek Sengupta1 · Priyanka Narad1 · Harshita Pandey1
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GYNECOLOGY

Improved Pregnancy Outcomes and Endometrial Receptivity by Thawed Frozen Embryo Transfer in Mildly Stimulated Cycles with Letrozole Combined with Estrogen in Women with Unresponsive Thin Endometrium Compared to Standard Endometrial Preparation with Estrogen Alone: A Retrospective Study

Narayana Nagaraja1 · S. D. Poddar2 · Seema Rai1 · Vishesh Verma3 · Kumar Abhisheka4 · Abha Khurana1

Context Infertile women undergoing frozen embryo transfer (FET) cycles may not show optimal endometrial growth with estrogens alone. Aim To evaluate clinical effect of mild stimulation with letrozole and estrogens on endometrial growth in comparison to standard endometrial preparation with oral and topical estrogens in infertile women with unresponsive thin endometrium undergoing FET. Settings and design Retrospective observational case–control study.

Material and methods Forty women unresponsive to first AC-FET cycle were given mild stimulation with letrozole and estrogens as second LE-FET cycle for endometrial preparation (LE-FET study group) and compared with 40 historical controls who had received two cycles of AC-FET (AC-FET control group). Responses were assessed by optimal endometrial thickness (≥ 7 mm) and clinical pregnancy.

Statistical analysis Descriptive statistics were elaborated by mean ± SD and percentages. Results were expressed by mean ± SD, unpaired t test for difference in endometrial thickness, chi square and Fisher exact test to compare the difference in pregnancy among both groups.

Results Mean endometrial thickness was significantly increased in LE-FET study group (6.68 ± 2.09 mm) versus AC-FET control group (5.35 ± 1.90 mm). Higher clinical pregnancy rate was noted in study group as compared to control group (35% versus 12.5%).

Conclusion This study suggests that letrozole with estradiol (LE-FET) compared to estradiol alone (AC-FET) for second cycle significantly increased endometrial thickness and improved clinical pregnancy rates in women with unresponsive thin endometrium after first AC-FET cycle with estradiol alone. Addition of letrozole to estrogen upfront for FET cycles may enhance endometrial receptivity and might improve pregnancy outcomes.

Letrozole · Infertility · Frozen embryo transfer · Endometrial thickness
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Compare Two Kinds of Recurrent MI‑Arrest Oocytes

Yan Jiang1 · Jing‑chuan Yuan1 · Ge Song1 · Xiao‑hua Wu1
ICSI · Re-ICSI · Recurrent MI-arrest oocytes · Indented ZP
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Infertility Management in India: Issues and Potential Solutions

Kandala Neela Amodini1 · Sirshendu Chaudhuri1
Infertility is a significant global issue affecting numerous couples, with India experiencing a considerable prevalence. Limited access to assisted reproductive technology centers and social stigmas result in underreporting and low service utilization. The financial burden of infertility treatment is substantial due to high costs and lack of insurance coverage. The absence of national guidelines and monitoring raises concerns about unethical practices. Standardizing ART practice and infertility management guidelines, integrating care into primary healthcare, and raising awareness to reduce social stigma can enhance the quality and accessibility of infertility treatment. India · Infertility · Reproductive Health · Reproductive health services
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