Preimplantation genetic testing for aneuploidy (PGT-A)-a single-center experience.

PURPOSE: The aim of this study was to determine the prevalence and nature of human embryonic aneuploidy based on the preimplantation genetic testing for aneuploidy (PGT-A), the distribution of aneuploidy across the individual chromosomes, and their relationship to maternal age. METHODS: This is a retrospective cohort study conducted at a single center. The study includes subjects who opted for PGT-A in their in vitro fertilization (IVF) cycle from 2016 to 2020. PGT-A was performed on 1501 embryos from 488 patients in 535 cycles. PGT-A was performed using NGS-based technique on Ion Torrent PGM (Life Technologies). Analysis was performed to determine the (i) frequency of the aneuploidy, (ii) the chromosome most commonly affected, (iii) relationship between maternal age and the rate of aneuploidy, and (iv) incidence of segmental aneuploidy. RESULTS: The overall frequency of aneuploidy was observed to be 46.8%. The incidence of aneuploidy rate was ~ 28% at maternal age < 30 years which steadily increased to ~ 67% in women above 40 years. High frequency of aneuploidy was observed in chromosomes 16, 22, 21, and 15. Segmental abnormalities, involving loss or gain of chromosomal fragments, were observed at a frequency of 5.3%, and highest incidence of segmental gain was observed on the q-arm of chromosome 9. CONCLUSION: The study provides important information regarding the frequency of the aneuploidy in IVF cohort and the most frequent chromosomal abnormality. The study further emphasizes the relationship between maternal age and aneuploidy. This study has important implications which help clinicians and genetic counselors in providing information in patient counseling.

Automated Follicular Assessment Using a Novel Two-dimensional Ultrasound-based Solution.

BACKGROUND: High intra- and interobserver variability in the follicular assessment using two-dimensional (2D) ultrasound (US) is still a concern. To solve this issue, we have developed a novel software solution, which automatically provides follicles' count and their diameters using 2D US images obtained by a manual sweep of an ovary. The primary objective of this study was to compare the result of the automated solution with a manual 2D US-based assessment. METHODS: In the first phase, multiple follicular US sweeps were collected from 54 subjects; these sweeps were used to develop the software. In the second phase, data from 10 subjects were collected for validation of the developed solution. During each phase, for follicles ≥5 mm, their count and diameters were recorded by the sonologist using 2D US. RESULTS: For the total follicle count, a high correlation (0.787) was observed between the solution and manual assessment. The 95% limits of agreement between the two methods were in the range of 4.232 to -4.258. The two methods had an excellent correlation (0.817) for the measurement of mean follicular diameter. However, the solution had a tendency to underestimate the mean diameter by an average of 1.725 mm (±2.16 mm). The limits of agreement between the two methods for mean diameter measurement were from 2.508 to -5.960 mm. CONCLUSION: This study validates the feasibility of our solution for automatic assessment of follicle count and diameter with accuracy comparable to the 2D US-based manual assessment. We further observed that the solution's performance is better than known intra- and interobserver variability of the manual assessment. We recommend further validation of the solution to confirm these initial results and potential time gain with an automated assessment.

The Development of an International Oncofertility Competency Framework: A Model to Increase Oncofertility Implementation.

BACKGROUND: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. Currently, oncofertility competencies do not exist. The aim of this study was to develop an oncofertility competency framework that defines the key components of oncofertility care, develops a model for prioritizing service development, and defines the roles that health care professionals (HCPs) play. MATERIALS AND METHOD: A quantitative modified Delphi methodology was used to conduct two rounds of an electronic survey, querying and synthesizing opinions about statements regarding oncofertility care with HCPs and patient and family advocacy groups (PFAs) from 16 countries (12 high and 4 middle income). Statements included the roles of HCPs and priorities for service development care across ten domains (communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, oncofertility training, reproductive survivorship care and fertility-related psychosocial support, supportive care, and ethical frameworks) that represent 33 different elements of care. RESULTS: The first questionnaire was completed by 457 participants (332 HCPs and 125 PFAs). One hundred and thirty-eight participants completed the second questionnaire (122 HCPs and 16 PFAs). Consensus was agreed on 108 oncofertility competencies and the roles HCPs should play in oncofertility care. A three-tier service development model is proposed, with gradual implementation of different components of care. A total of 92.8% of the 108 agreed competencies also had agreement between high and middle income participants. CONCLUSION: FP guidelines establish best practice but do not consider the skills and requirements to implement these guidelines. The competency framework gives HCPs and services a structure for the training of HCPs and implementation of care, as well as defining a model for prioritizing oncofertility service development. IMPLICATIONS FOR PRACTICE: Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. The competency framework gives 108 competencies that will allow health care professionals (HCPs) and services a structure for the development of oncofertility care, as well as define the role HCPs play to provide care and support. The framework also proposes a three-tier oncofertility service development model which prioritizes the development of components of oncofertility care into essential, enhanced, and expert services, giving clear recommendations for service development. The competency framework will enhance the implementation of FP guidelines, improving the equitable access to medical and psychological oncofertility care.

HLA allele frequency of HLA-A, -B, -C, -DRB1 and -DQB1 in Indian recurrent implantation failure and recurrent pregnancy loss couples - A retrospective study.

The maternal-fetal interaction has been hypothesized to involve the human leucocyte antigen (HLA). It has been suggested that excessive HLA antigen sharing between spouses is a mechanism causing maternal hyporesponsiveness to paternal antigens encountered during pregnancy and thus leading to a miscarriage. Participants in this retrospective study are RIF and RPL couples who visited Gunasheela Surgical and Maternity Hospital, Bangalore, India from November 2019 to September 2022. A total of 40 couples with RIF and 195 couples with RPL are included in the study. We observed that the DQB1*02:01:01 allele is associated with an increase in risk of both RIF and RPL, while the C*12:02:01 allele increases risk of only RPL. On the contrary, DQB1*02:02:01 and DQB1*06:03 alleles appear to be protective against both RPL and RIF. In addition, the C*07:02:01 allele was observed to be protective against RPL. In conclusion, C*12:02:01 and DQB1*02:01:01 could play a major role in RPL which is consistent with other studies, while DQB1*02:01:01 is the risk allele in our RIF group. The protective alleles C*07:02:01 in the RPL group, DQB1*02:02:01, and DQB1*06:03 in both RIF and RPL, were discovered for the first time. Allele frequencies will vary in population-based studies depending on the ethnicities of the cohort. Meta-analysis and antibody testing will provide additional insights on whether and how this data can be adopted into clinical practices.

Cumulative Live Birth Rate per Oocyte Aspiration in Artificial Reproduction Technology: A Retrospective Observational Study of the Association between Maternal Age and the Number of Oocytes Retrieved in an Indian Population.

Background: The association between cumulative live birth rate (CLBR) and oocyte aspiration in the context of maternal age is not well understood in the Indian population. Aims: To find the relationship between CLBR and a single oocyte aspiration. Settings and Design: This is a retrospective study analysing the data of 1989 women who underwent in vitro fertilisation (IVF) between January 2015 and December 2019, at Gunasheela Surgical and Maternity Hospital, India. Materials and Methods: Participants were divided into two groups based on age: ≤35 (group I, n = 1665) and >35 (Group II, n = 324). CLBR per single oocyte aspiration in fresh and subsequent three frozen embryo transfer cycles was estimated. Statistical Analysis Used: Logistic regression analysis was used to show the likelihood of pregnancy rate, and CLBR per aspiration after treatment was represented as odd's ratios (OR) with 95% confidence intervals. Results: Maximal CLBR for Groups I and II was 81.25% with >25 oocytes and 75% with 16-20 oocytes, respectively. In the fresh ET cycle, maximal pregnancy and live birth rates were observed in 6-10 oocytes for Group I (54% and 41%) and in 16-20 oocytes for Group II (75% and 75%). The ORs for pregnancy rate (P = 0.01) and CLBR (P = 0.007) increased with an increase in the number of oocytes retrieved. The ORs for pregnancy rate and CLBR for Group II were 0.68 (P = 0.002) and 0.58 (P = 0.00002), respectively as compared to Group I. Optimal oocytes required to achieve positive IVF outcomes in fresh/frozen ET cycles were low in Group I (6-10 oocytes), but higher in Group II (16-20 oocytes). Conclusion: Robust positive relationship was observed between the number of oocytes retrieved and CLBR in women of both age groups.

The Use of Integrative Medical Services to Address Psychological Concerns around Infertility in an Indian Academic Medical Centre.

Background: Alternative and complementary therapies have been gaining popularity as ways to reduce anxiety in patients. Aim: This study aimed to assess whether yoga and meditation could decrease the severity of anxiety in Indian women diagnosed with infertility Study. Study Setting and Design: This was a retrospective data analysis of anxiety score of 354 women undergoing treatment at a tertiary infertility hospital between January 2016 and December 2018. Materials and Method: Women participated in group yoga, meditation and counselling therapy intervention during their treatment period. A self-reported questionnaire that used the Generalised Anxiety Disorder-7 criteria measured the participants' severity of anxiety at the start of and again at the end of the intervention. Statistical Analysis: Demographic analysis and a two-tailed paired t-test were applied between groups. Results: The results indicated that there was a statistically significant mean reduction (7.3 ± 2.7) in the anxiety scores of the participants between entry (12.94 ± 2.65) and following exposure (5.39 ± 1.99) to the intervention (P < 0.0001). The mean reduction in scores remained similar between participants who received ≤6 sessions (7.50 ± 2.68) and participants who received >6 sessions (7.10 ± 2.64) (P > 0.05). Among the participants that experienced mild anxiety at baseline (n = 43), 72.1% (n = 31) reported experiencing minimal anxiety following the intervention (P < 0.0001). Among those that experienced moderate anxiety at baseline (n = 213), 32.4% (n = 69) reported experiencing minimal anxiety post-intervention (P < 0.0001). Participants who expressed severe anxiety at baseline (n = 94, 26.6%), reported experiencing minimal anxiety (13.8% [n = 13)], mild anxiety (81.9% [n = 77]) and moderate anxiety (4.3% [n = 4]) after exposure to the intervention (P < 0.0001). None of the participants reported experiencing severe anxiety post-intervention. Conclusion: The benefits of alternative anxiety-reduction therapies for women diagnosed with infertility have been demonstrated in this study. These therapies can be used to complement the routine treatment of such patients.

Preimplantation Genetic Testing for Couples with Balanced Chromosomal Rearrangements.

Background: Chromosomal rearrangements play an important role in infertility. Carriers of chromosomal rearrangements have a lower chance of producing normal or balanced gametes due to abnormal segregation of chromosomes at meiosis, which leads to recurrent spontaneous abortions and infertility. Preimplantation genetic testing for structural chromosome rearrangements (PGT-SR) is offered to couples who have balanced chromosomal rearrangements in order to select embryos with a balanced karyotype prior to implantation, thereby increasing the chances of pregnancy. The purpose of the current study was to assess the outcomes of PGT-SR in patients carrying various balanced chromosomal rearrangements and to assess their clinical pregnancy outcome after in vitro fertilization (IVF). Methods: In this study, infertile couples with balanced chromosomal abnormalities undergoing PGT-SR were retrospectively analyzed at a single fertility center from January 2016 to December 2019. Results: PGT-SR was performed on 87 embryos from 22 couples in whom one partner carried a balanced translocation or an inversion. Fifty-seven (65.5%) of these embryos had unbalanced or sporadic aneuploidies, 30 (34.5%) embryos were normal or chromosomally balanced, which were then transferred in 18 couples. A higher rate of unbalanced translocations in comparison to sporadic aneuploidies was observed in couples with reciprocal translocation. The live birth rate per embryo transfer was found to be 66.6% (12/18). Conclusion: PGT-SR is a useful tool in selecting normal or balanced embryos for transfer in IVF, which could lead to a pregnancy by reducing the chance of miscarriages due to chromosome aneuploidy in couples with balanced chromosomal rearrangements.

A Study to Find Optimal Intra-cytoplasmic Sperm Injection Timing of Oocytes Matured from Germinal Vesicle in in Vitro Maturation Cycles Using a Time Lapse System.

BACKGROUND: The use of in vitro maturation (IVM) has allowed patients with polycystic ovary syndrome (PCOS) to have a positive fertility outcome, as it allows utilisation of immature oocytes to mature in vitro. AIM: The aim of the study is to establish an optimum intra-cytoplasmic sperm injection (ICSI) timing for IVM oocytes (germinal vesicles [GV] →, metaphase I [MI]→ and metaphase II [MII]) using time lapse system (TLS) for patients with PCOS. SETTING AND DESIGN: Patients included in this study were diagnosed with PCOS, ≤35 years of age, anti-Müllerian hormone levels >6 ng/ml and antral follicle counts <40. Furthermore, we included only GV oocytes at the time of denudation in our study. MATERIALS AND METHODS: Patients were minimally stimulated and their oocytes were retrieved. In vitro maturated oocytes were monitored using TLS to a maximum of 30 h. MII oocytes were further cultured and injected at five different time intervals (1-2 h, 3-4 h, 5-6 h, 7-8 h and >8 h) to observe for fertilisation, cleavage and utilisation rate. STATISTICAL ANALYSIS: Chi-square test was applied to compared the treatment groups. RESULTS: Amongst 328 oocytes retrieved from 27 female patients, 162 oocytes were in the time-monitored cohort and 162 oocytes were grouped as the control cohort. Maturation rate between GV→ MII was highest at 18 h in the time-monitored cohort MII (n = 57). Utilisation rate was highest when ICSI was performed between 5 and 6 h after the first polar body extrusion, n = 17 (63%). CONCLUSION: This study provides valuable insight into the optimal maturation timing using a TLS to yield the good number of oocytes. In addition, optimising ICSI timing is important to provide the best utilisation rate in an IVM cycle to achieve synchrony between nuclear and cytoplasmic maturation.

A Descriptive Study Exploring Semen Quality Among Indian Cancer Patients.

Purpose: To descriptively explore semen quality among Indian men with various types of malignancies. We evaluated semen parameters of male patients referred to our hospital before commencing their cancer treatment. Methods: Four hundred sixty-one male patients who were within the age range of 15-50 years were recruited with diagnosed malignancies. Pre-treatment semen analyses were performed on these patients to collect data on the volume, sperm concentration, motility, and normal forms (morphology). These semen parameters were compared between cancer groups (testicular cancer, hematological cancer, and other cancers). Further comparisons were also drawn to World Health Organization (WHO) semen parameter levels (2010, fifth edition) for normal outcomes. Results: There were no notable variations observed in semen volume (mL) and progressive motility (%) between cancer groups. These parameters were within the WHO normal semen criteria. Differences in normal forms (%) between cancer groups were not observed either; however, they were marginally lower compared with the WHO criteria. Sperm concentration was evidently lower in testicular cancer 34 × 106/mL (IQR: 10.1-60 × 106/mL) compared with hematological cancers 66 × 106/mL (IQR: 23-84.21 × 106/mL) and other cancers (IQR: 27-86.3 × 106/mL). Testicular cancer patients also presented with the largest semen disorder diagnosis (Asthenozoospermia, Oligoasthenozoospermia, Oligozoospermia, and Azoospermia) compared with two other groups. Conclusion: Males with testicular cancer have shown to have lower semen quality between cancer groups and compared with WHO criteria, increasing their likelihood of them being infertile. This study further allows us to understand these outcomes, particularly in the Indian subpopulation, propagating changes in guidelines in oncofertility and medical counseling. Clinical Trials Registry-India number: CTRI/2020/09/027720.

Age-Specific Distribution of Serum Anti-Mullerian Hormone and Antral Follicle Count in Indian Infertile Women.

BACKGROUND: Ovarian reserve declines with age. However, there are considerable ethnic differences in the decline of ovarian reserve between individuals. AIM: This study aimed to make age-specific percentile charts of anti-Mullerian hormone (AMH) and antral follicle count (AFC) in Indian infertile women and to find the proportion of young women with low ovarian reserve. SETTING AND DESIGN: This was a retrospective data analysis of AMH and AFC of 5525 infertile women from August 2015 to December 2018. MATERIALS AND METHODS: Infertile women aged 20- 44 years, with body mass index 18-32 kg/m2 and having both ovaries were included in the study. Women with pituitary/adrenal disorders, malignancy, total AFC >40, tuberculosis, endometriosis, autoimmune disorders, smoking, chemotherapy, radiotherapy and recent ovarian surgery were excluded from the study. STATISTICAL ANALYSIS: Comparison between groups was done by Chi-square test. RESULTS: About 14.5% of women <35 years and 50.5% of women >35 years had low AMH values (<1.1 ng/ml). In addition, 5.6% of women <35 years and 23.6% of women >35 years had a low AFC of ≤5. In this study, 55.7% of women who had low AMH and 50.7% who had low AFC were <35 years of age. The median AMH values were 4.23 ng/mL in 20-25 years' age group, 3.48 ng/mL in women aged 26-30 years, 2.43 ng/mL in women aged 31-35 years, 1.28 ng/mL in women aged 36-40 years and0.52 ng/mL in 40-44 years' age group. The median AFCs were 20, 18, 14, 10 and 6 for each of the age groups, respectively. CONCLUSION: This study suggests that approximately more than half of the infertile women who were tested to have low ovarian reserve were <35 years of age.

A Study on Diagnostic Evaluation of Two Different Rapid DNA Polymerase Chain Reaction Techniques Namely Gene Xpert Mycobacterium Tuberculosis/Rifampin (MTB/RIF) and Mycoreal Polymerase Chain Reaction in the Diagnosis of Endometrial Tuberculosis Considering Culture as Gold Standard.

CONTEXT: The study involves the evaluation of two polymerase chain reaction (PCR) techniques one of which has been endorsed by the WHO for their diagnostic capabilities. AIMS: The aim of this study is to evaluate the diagnostic accuracy of GeneXpert mycobacterium tuberculosis/Rifampin (MTB/RIF) and mycoreal PCR techniques in the diagnosis of endometrial tuberculosis (TB) considering culture as the gold standard. SETTINGS AND DESIGN: A retrospective study conducted at Gunasheela surgical and maternity hospital. Patients who attended the outpatient department between January 2013 and August 2016, satisfying the eligibility criteria, were included in the study. METHODOLOGY: Women included in the study underwent endometrial pipelle sampling premenstrually after ruling out pregnancy in that cycle. Endometrial samples were tested for TB by Mycoreal PCR, Gene Xpert and BACTEC culture. STATISTICAL ANALYSIS USED: Statistical analysis was done using the R software version 3.6.1. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of test were calculated. RESULTS: A total of 3229 samples were analyzed, of which 1754 were evaluated by Mycoreal TB PCR and 1475 were evaluated by Gene Xpert MTB/RIF assay. The sensitivity of mycoreal TB PCR technique was 34.78%, specificity was 99.08%, PPV was 33.33%, NPV was 99.13%, and accuracy was 98.23%. The sensitivity of GeneXpert MTB/RIF technique was 6.90%, specificity was 99.79%, PPV was 40.00%, NPV was 98.16%, and accuracy was 97.97%. CONCLUSIONS: MYCOREAL seemed to be more sensitive than Gene Xpert (MTB/RIF) considering culture as the gold standard in the diagnosis of endometrial TB.

How can we improve oncofertility care for patients? A systematic scoping review of current international practice and models of care.

BACKGROUND: Fertility preservation (FP) is an important quality of life issue for cancer survivors of reproductive age. Despite the existence of broad international guidelines, the delivery of oncofertility care, particularly amongst paediatric, adolescent and young adult patients, remains a challenge for healthcare professionals (HCPs). The quality of oncofertility care is variable and the uptake and utilization of FP remains low. Available guidelines fall short in providing adequate detail on how oncofertility models of care (MOC) allow for the real-world application of guidelines by HCPs. OBJECTIVE AND RATIONALE: The aim of this study was to systematically review the literature on the components of oncofertility care as defined by patient and clinician representatives, and identify the barriers, facilitators and challenges, so as to improve the implementation of oncofertility services. SEARCH METHODS: A systematic scoping review was conducted on oncofertility MOC literature published in English between 2007 and 2016, relating to 10 domains of care identified through consumer research: communication, oncofertility decision aids, age-appropriate care, referral pathways, documentation, training, supportive care during treatment, reproductive care after cancer treatment, psychosocial support and ethical practice of oncofertility care. A wide range of electronic databases (CINAHL, Embase, PsycINFO, PubMed, AEIPT, Education Research Complete, ProQuest and VOCED) were searched in order to synthesize the evidence around delivery of oncofertility care. Related citations and reference lists were searched. The review was undertaken following registration (International prospective register of systematic reviews (PROSPERO) registration number CRD42017055837) and guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). OUTCOMES: A total of 846 potentially relevant studies were identified after the removal of duplicates. All titles and abstracts were screened by a single reviewer and the final 147 papers were screened by two reviewers. Ten papers on established MOC were identified amongst the included papers. Data were extracted from each paper and quality scores were then summarized in the oncofertility MOC summary matrix. The results identified a number of themes for improving MOC in each domain, which included: the importance of patients receiving communication that is of a higher quality and in different formats on their fertility risk and FP options; improving provision of oncofertility care in a timely manner; improving access to age-appropriate care; defining the role and scope of practice of all HCPs; and improving communication between different HCPs. Different forms of decision aids were found useful for assisting patients to understand FP options and weigh up choices. WIDER IMPLICATIONS: This analysis identifies core components for delivery of oncofertility MOC. The provision of oncofertility services requires planning to ensure services have safe and reliable referral pathways and that they are age-appropriate and include medical and psychological oncofertility care into the survivorship period. In order for this to happen, collaboration needs to occur between clinicians, allied HCPs and executives within paediatric and adult hospitals, as well as fertility clinics across both public and private services. Training of both cancer and non-cancer HCPs is needed to improve the knowledge of HCPs, the quality of care provided and the confidence of HCPs with these consultations.

Strategies for fertility preservation in young patients with cancer: a comprehensive approach.

As a result of treatment innovations, the survival rates of young people with cancer have increased substantially. The cancers most frequently diagnosed in adults aged 25-49 years include breast, colorectal and cervical cancer and malignant melanoma (Cancer Research UK, 2009). The 5-year survival rates of over 90 % for many malignancies are now reported in young people. But the diagnosis and treatment of cancer often poses a threat to fertility. Methods of fertility preservation are evolving quickly and awareness needs to grow in the medical community regarding these methods. Studies suggest that the ability to have biological children is of great importance to many people. The possible future effects of chemotherapy or radiotherapy on fertility should be discussed with all cancer patients who have reproductive potential. Moreover, fertility preservation should be considered for all young people undergoing potentially gonadotoxic treatment. This article covers the various methods of fertility preserving options in young men and women with respect to the various treatment modalities that they may be subjected to. Sperm banking is a simple and low cost intervention. Embryo cryopreservation is the only established method of female fertility preservation. Oocyte cryopreservation offers a useful option for women without a male partner. Emergency ovarian stimulation and cryopreservation of ovarian tissue (followed by tissue transplantation or in-vitro maturation of oocytes) are experimental techniques for women who require urgent cancer treatment. Large, well-controlled studies are also required to identify any unexpected long-term sequelae of cryopreservation of oocytes and ovarian tissue.

Luteinizing hormone and follicle stimulating hormone synergy: A review of role in controlled ovarian hyper-stimulation.

Luteinizing hormone (LH) in synergy with follicle stimulating hormone (FSH) stimulates normal follicular growth and ovulation. FSH is frequently used in assisted reproductive technology (ART). Recent studies have facilitated better understanding on the complementary role of the LH to FSH in regulation of the follicle; however, role of LH in stimulation of follicle, optimal dosage of LH in stimulation and its importance in advanced aged patients has been a topic of discussion among medical fraternity. Though the administration of exogenous LH with FSH is obligatory for controlled ovarian stimulation in patients with hypogonadotropic hypogonadism, there is still a paucity of information of its usage in other patient population. In this review we looked in to the multiple roles that LH plays complementary to FSH to better understand the LH requirement in patients undergoing ART.