The impact of follicular fluid phthalate metabolites on the ovarian reserve and ovarian function in Indian women undergoing intracytoplasmic sperm injection.

OBJECTIVE: To investigate the adverse effects of phthalate-induced ovarian toxicity on the ovarian reserve and ovarian function. To assess whether the accumulation of higher levels of selected phthalate metabolites in the follicular fluid (FF) of Indian women undergoing intracytoplasmic sperm injection (ICSI) was associated with a decline in their antral follicle count (AFC) and/or serum antimüllerian hormone (AMH) levels, suggesting a negative impact on the ovarian reserve. To evaluate the effects of follicular phthalate metabolites on peak serum estradiol (E2) levels and the total number of oocytes and mature metaphase II (MII) stage oocytes retrieved to assess the impact of phthalate toxicity on ovarian function. DESIGN: A subanalysis of an ongoing prospective cohort study was conducted to examine the association between the levels of six phthalate metabolites, namely, mono-n-butyl phthalate (MBP), mono-ethyl phthalate (MEP), mono-isononyl phthalate (MiNP), mono-isodecyl phthalate (MiDP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate, in the FF of Indian women undergoing ICSI and their ovarian reserve markers (AFC and serum AMH levels). To investigate the association of these follicular phthalate metabolite levels with the peak E2 levels and the total number of oocytes and number of MII stage oocytes retrieved. SETTING: In vitro fertilization center in a referral hospital in India. PATIENT(S): A total of 245 consenting Indian women who had undergone oocyte retrieval between April 2017 and mid-March 2020 were included. Each woman contributed one FF sample to the study. This was screened for six phthalate metabolites. The samples were collected before the coronavirus disease 2019 pandemic. INTERVENTION(S): Using liquid chromatography-tandem mass spectrometry, the total levels of six phthalate metabolites were quantified in the FF of 245 women. Using linear regression models that were unadjusted and adjusted for maternal age and body mass index (BMI), we evaluated the association between the follicular metabolites in these women and their AFC, serum AMH levels, peak E2 levels, total number of oocytes, and MII stage oocytes. MAIN OUTCOME MEASURE(S): To evaluate the impact of phthalate-induced ovarian toxicity on the ovarian reserve and ovarian function in Indian women undergoing ICSI by studying their accumulated levels in their FF. RESULT(S): For MiNP (a metabolite of di-isononyl phthalate), in linear regression models adjusted for age and BMI, we found that with increasing quartiles of follicular MiNP, there was a significant trend in the decrease in mean AFC (P-trend = 0.023) and a suggestive trend in the decrease in mean serum AMH levels (P-trend = 0.077). For MiDP (a metabolite of di-isodecyl phthalate), in the unadjusted regression model, we found that with increasing quartiles of follicular MiDP, there was a significant trend in the decrease in mean serum AMH levels (P-trend = 0.045). For MBP (a metabolite of dibutyl phthalate), in linear regression models adjusted for age and BMI, we found that with increasing quartiles of follicular MBP, there were significant trends in the decrease in the mean number of total oocytes retrieved (P-trend = 0.003), a decrease in the mean number of MII stage oocytes retrieved, (P-trend = 0.003) and a decrease in the mean peak E2 levels (P-trend = 0.016). Although we found that with increasing quartiles of follicular mono(2-ethyl-5-oxohexyl) phthalate there was a decrease in the mean number of total and MII stage oocytes retrieved and higher follicular MEP levels were negatively associated with the mean AFC and serum AMH levels, neither trend was statistically significant. We also found that although follicular MEP levels did not show an adverse impact on ovarian function, follicular mono(2-ethyl-5-hydroxyhexyl) phthalate levels did not show an adverse impact on both the ovarian reserve and function. CONCLUSION: In this study of 245 Indian women, higher accumulated FF levels of MiNP and MiDP were negatively associated with AFC and serum AMH levels, suggesting an adverse effect on the ovarian reserve. Higher accumulated FF levels of MBP were negatively associated with the total number of oocytes, MII stage oocytes, and peak E2 values, suggesting a negative impact on ovarian function. Although we found that phthalate-induced ovarian toxicity was statistically significant for selected phthalate metabolites, the role of the cumulative effect of multiple phthalates in the ovarian microenvironment cannot be ruled out and needs to be investigated further.

Oncofertility and Pregnancy in Adolescent and Young Adult Cancers: Physicians' Knowledge and Preferences in India.

PURPOSE: The treatment outcomes of adolescent and young adult (AYA) cancers have improved with advanced oncology care. Hence, fertility preservation (FP) and post-therapy pregnancies (PTPs) become vital issues. MATERIALS AND METHODS: An online survey link with 17 questions regarding oncofertility and PTPs was circulated among oncologists to assess the knowledge, understand the oncofertility care patterns, and seek suggestions to improve oncofertility services. RESULTS: The median age of 179 respondents, predominantly medical oncologists (68.7%), was 37 years (IQR, 10; range, 29-74), working in academic centers (39%) having a median experience of 4 years (IQR, 4; range, 1-42); 23 (12.8%) had dedicated AYA cancer units. Although a quarter (19%-24%) of respondents discussed fertility issues in >90% of AYA patients with cancer, only a tenth (8%-11%) refer >90% for FP, with significantly higher (P < .05) discussions and referrals in males and by more experienced oncologists (P < .05). Forty-six (25.6%) were not well versed with international guidelines for FP. Most (122, 68.1%) oncologists knew about the referral path for semen cryopreservation; however, only 46% were knowledgeable about additional complex procedures. One hundred and ten (61.5%) oncologists never or rarely altered the systemic treatment for FP. Prominent barriers to FP were ignorance, lack of collaboration, and fear of delaying cancer treatment. Lead thrust areas identified to improve FP practices are education, and enhanced and affordable access to FP facilities. Seventy-four (41.3%) respondents knew about international guidelines for PTPs; however, only half (20%) of them often monitored fertility outcomes in survivors. Oncologists have conflicting opinions and uncertainties regarding pregnancy safety, assisted reproductive techniques, breastfeeding, and pregnancy outcomes among survivors. CONCLUSION: Oncologists are uncertain about the guidelines, FP practices, referral pathways, and PTPs. Multipronged approaches to improve awareness and provision for affordable oncofertility facilities are needed to enhance AYA cancer outcomes in India, which will be applicable to other low- and middle-income countries too.

Semen proteomics reveals alterations in fertility-related proteins post-recovery from COVID-19.

Introduction: Changes to sperm quality and decline in reproductive function have been reported in COVID-19-recovered males. Further, the emergence of SARS-CoV-2 variants has caused the resurgences of COVID-19 cases globally during the last 2 years. These variants show increased infectivity and transmission along with immune escape mechanisms, which threaten the already burdened healthcare system. However, whether COVID-19 variants induce an effect on the male reproductive system even after recovery remains elusive. Methods: We used mass-spectrometry-based proteomics approaches to understand the post-COVID-19 effect on reproductive health in men using semen samples post-recovery from COVID-19. The samples were collected between late 2020 (1st wave, n = 20), and early-to-mid 2021 (2nd wave, n = 21); control samples were included (n = 10). During the 1st wave alpha variant was prevalent in India, whereas the delta variant dominated the second wave. Results: On comparing the COVID-19-recovered patients from the two waves with control samples, using one-way ANOVA, we identified 69 significantly dysregulated proteins among the three groups. Indeed, this was also reflected by the changes in sperm count, morphology, and motility of the COVID-19- recovered patients. In addition, the pathway enrichment analysis showed that the regulated exocytosis, neutrophil degranulation, antibacterial immune response, spermatogenesis, spermatid development, regulation of extracellular matrix organization, regulation of peptidase activity, and regulations of calcium ion transport were significantly dysregulated. These pathways directly or indirectly affect sperm parameters and function. Our study provides a comprehensive landscape of expression trends of semen proteins related to male fertility in men recovering from COVID-19. Discussion: Our study suggests that the effect of COVID-19 on the male reproductive system persists even after recovery from COVID-19. In addition, these post-COVID-19 complications persist irrespective of the prevalent variants or vaccination status.

The status of anti-ovarian antibody immunoassays: Valid or invalid, in or out?

There has been a paradign shift in the status of immunoassays. There used to be a time where immunoassays had a very narrow role in clinical medicine, but that is not the case in today's world. Immunoassays have taken a central role in helping us better understand and treat human diseases. The literature around anti-ovarian antibodies (AOA) immunoassay testings have been conflicting. Researchers challenged the specificity of the reported assays, but a systematic study was never elucidated on what/who the trouble maker was in rendering these tests so nonspecific. Attempts were made by our group in Mumbai, India, to throw light on the culprit behind the nonspecificity casative factor in the immunoassays and a method to overcome this was reported and published. This review highlights the stories back five and a half decades to date, to demonstrate where the status of AOA testing was, is and will be.

Genetic counseling for pre-implantation genetic testing of monogenic disorders (PGT-M).

Pre-implantation genetic testing (PGT) is a vital tool in preventing chromosomal aneuploidies and other genetic disorders including those that are monogenic in origin. It is performed on embryos created by intracytoplasmic sperm injection (ICSI). Genetic counseling in the area of assisted reproductive technology (ART) has also evolved along with PGT and is considered an essential and integral part of Reproductive Medicine. While PGT has the potential to prevent future progeny from being affected by genetic conditions, genetic counseling helps couples understand and adapt to the medical, psychological, familial and social implications of the genetic contribution to disease. Genetic counseling is particularly helpful for couples with recurrent miscarriages, advanced maternal age, a partner with a chromosome translocation or inversion, those in a consanguineous marriage, and those using donor gametes. Partners with a family history of genetic conditions including hereditary cancer, late onset neurological diseases and with a carrier status for monogenic disorders can benefit from genetic counseling when undergoing PGT for monogenic disorders (PGT-M). Genetic counseling for PGT is useful in cases of Mendelian disorders, autosomal dominant and recessive conditions and sex chromosome linked disorders and for the purposes of utilizing HLA matching technology for creating a savior sibling. It also helps in understanding the importance of PGT in cases of variants of uncertain significance (VUS) and variable penetrance. The possibilities and limitations are discussed in detail during the sessions of genetic counseling.

First Report of an α Chain Variant [Hb Coombe Park (HBA2: c.382A>G)] from India, Coinherited with a Novel SERPINC1 Gene Mutation: A Double Whammy?

Coinheritance of a high oxygen affinity structural hemoglobin (Hb) variant along with a thrombophilia marker is a rare occurrence. This may lead to a multi fold increase in the risk of thrombosis in patients. We report here a first case of Hb Coombe Park (HBA2: c.382A>G; p.Lys128Glu) from India, coinherited with a novel mutation (c.839C>G; p.Ser280Ter) on the SERPINC1 gene. This coinheritance has not been reported before. Though the patient is presently asymptomatic, identification of these variants will help in genetic counseling and to decide the future course of action in case of any clinical complications.

Dysfunctional regulation of pivotal and key inflammatory pathways in infertile Indian women with genital tuberculosis.

PROBLEM: Diagnosis of female genital tuberculosis (FGTB) remains elusive due to the paucibacillary nature of the disease. We evaluated if analysis of inflammatory pathways of endometrial tissue could establish a better diagnosis of FGTB. METHOD OF STUDY: One hundred and four infertile women suspected of having GTB or having been treated for GTB in the past, underwent endometrial biopsies for diagnosis and Gene Inflammatory Pathways analysis at our center between 2018-2020. Diagnosis of FGTB was based on acid-fast bacilli culture, immunocytochemistry, nested-polymerase chain reaction, histopathological examination, TB GeneXpert, or combinations thereof. Gene expression profiles were also analyzed. RESULTS: Based on diagnostic tests of 104 women, 44 (42%) were considered TB-positive, 35 (34%) TB-negative, and 25 (24%) TB-negative after TB treatment in the past. Inflammatory pathways were significantly upregulated in TB-positive women versus TB-negative (41% vs. 6%; p = .0005), and in women who were TB-negative after TB treatment in the past versus TB-negative (never treated for TB in the past) (38% vs. 6%; p = .0037). Two-hundred seventy-one genes were upregulated, and 61 genes were downregulated in TB-positive women versus those who were TB-negative. Differentially expressed genes were mapped to various interlinked inflammatory signaling pathways, including mitogen-activated protein kinase (MAPK), Natural Killer (NK) cells, nuclear factor kappa-B (NF-kB), tumor necrosis factor (TNF), and Toll-like receptors (TLR) signaling. CONCLUSIONS: Inflammatory pathways and gene expression profiles add to the diagnostic tools to identify TB-positive women at an early stage. The results from this study are still experimental and large multi-centric studies are suggested before their recommendation in routine clinical practice.

Significant changes in follicular fluid phthalate metabolite levels reflect the lifestyle changes brought about by the strict COVID-19 lockdown in India.

OBJECTIVE: To assess if the unprecedented changes in lifestyle because of the lockdown initiated by the COVID-19 pandemic, which altered human behavior, and influenced purchase and consumption patterns, may have had an impact on the exposure to phthalates in Indian women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). To evaluate if the effects of the strict and lengthy lockdown in India, which promoted the new norms of stay-at-home and work-from-home, closure of beauty parlors, and restriction on public gatherings, may have contributed to a decrease in the exposure to phthalates like dibutyl phthalate and diethyl phthalate. These chemicals are found in many personal care products (PCPs) which include cosmetics and fragrances. To investigate if the extensive use of flexible single-use plastic in personal protective equipment like face masks/gloves and in plastic packaging used for online purchases, food takeaways, and home deliveries of essentials and groceries during the COVID-19 pandemic, in an attempt to provide a contact-free delivery system may have inadvertently led to an increase in exposure to phthalates like di(2-ethylhexyl) phthalate, di-isononyl phthalate, and di-isodecyl phthalate which are plasticizers used in manufacturing flexible plastic. DESIGN: A comparative study of the levels of six phthalate metabolites detected in follicular fluid (FF) of Indian women undergoing IVF/ICSI 1 year before and immediately after the lockdown initiated by the COVID-19 pandemic. SETTING: In vitro fertilization center in a large referral hospital in India. PATIENT(S): A total of 176 Indian women seeking treatment for infertility and undergoing oocyte retrieval were included after obtaining consent. Each woman contributed one FF sample to the study. Group A (n = 96) women (mean age, 34.0 [±3.9] years, and mean BMI, 25.4 [±4.8]) had their FF samples collected and screened between January 2019 and mid-March 2020, 1 year before the lockdown. Group B (n = 80) women (mean age, 33.9 [±4.1] years, and mean BMI, 25.0 [±4.4]) had their FF collected and screened post the lockdown between October 2020 and June 2021. Both groups were matched by age and BMI. INTERVENTION(S): The cryopreserved FF samples of 176 women were processed using enzymatic deconjugation as well as the solid-phase extraction technique, and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect the total levels of six phthalate metabolites. MAIN OUTCOME MEASURE(S): To evaluate the impact of the COVID-19 lockdown on the change in the phthalate metabolite levels in the FF of Indian women undergoing IVF/ICSI pre and post the lockdown. RESULT(S): The median levels of mono-n-butyl phthalate (1.64 ng/ml in group A vs. 0.93 ng/ml in group B; P<.001) and mono-ethyl phthalate (5.25 ng/ml in group A vs. 3.24 ng/ml in group B; P<.001) metabolites of dibutyl phthalate and diethyl phthalate found in PCPs including cosmetics and fragrances were significantly higher in the FF of 96 women (group A) compared with the levels seen in the FF of 80 women (group B). However, the median levels of mono-isononyl phthalate (0.11ng/ml in group A vs. 0.13 ng/ml in group B; P<.001), mono-isodecyl phthalate (0.11 ng/ml in group A vs. 0.14 ng/ml in group B; P<.001), and mono(2-ethyl-5-oxohexyl) phthalate (0.13 ng/ml in group A vs. 0.14 ng/ml in group B; P=.023) metabolites of di-isononyl phthalate, di-isodecyl phthalate, and di(2-ethylhexyl) phthalate used as plasticizers were significantly higher in the FF of women in group B compared with women in group A. CONCLUSION(S): The significant drop in mono-n-butyl phthalate and mono-ethyl phthalate levels, accumulated in the FF of 80 Indian women in group B reflects a decrease or absence of usage patterns of PCPs, including cosmetics and fragrances, thereby suggesting that these women may have deprioritized their use during the COVID-19 pandemic giving preference to personal hygiene and safety. Whereas the unprecedented increase in the use of flexible single-use plastic that became our first line of defense against the coronavirus during the COVID-19 pandemic might be responsible for the accumulation of significantly higher levels of mono-isononyl phthalate, mono-isodecyl phthalate, and mono(2-ethyl-5-oxohexyl) phthalate in FF of the same group.

Semen Proteomics of COVID-19 Convalescent Men Reveals Disruption of Key Biological Pathways Relevant to Male Reproductive Function.

A considerable section of males suffered from COVID-19, with many experiencing long-term repercussions. Recovered males have been documented to have compromised fertility, albeit the mechanisms remain unclear. We investigated the impact of COVID-19 on semen proteome following complete clinical recovery using mass spectrometry. A label-free quantitative proteomics study involved 10 healthy fertile subjects and 17 COVID-19-recovered men. With 1% false discovery rate and >1 unique peptide stringency, MaxQuant analysis found 1099 proteins and 8503 peptides. Of the 48 differentially expressed proteins between the healthy and COVID-19-recovered groups, 21 proteins were downregulated and 27 were upregulated in COVID-19-recovered males. The major pathways involved in reproductive functions, such as sperm-oocyte recognition, testosterone response, cell motility regulation, adhesion regulation, extracellular matrix adhesion, and endopeptidase activity, were downregulated in COVID-19-recovered patients according to bioinformatics analysis. Furthermore, the targeted approach revealed significant downregulation of semenogelin 1 and prosaposin, two proteins related to male fertility. Therefore, we demonstrate the alteration of semen proteome in response to COVID-19, thus disrupting the male reproductive function despite the patient's clinical remission. Hence, to understand fertility-related biological processes triggered by this infection, a protracted evaluation of the consequences of COVID-19 in recovered men is warranted.

Evolution and Utility of Preimplantation Genetic Testing for Monogenic Disorders in Assisted Reproduction - A Narrative Review.

Preimplantation genetic testing (PGT) for monogenic disorders and assisted reproductive technology have evolved and progressed in tandem. PGT started with single-cell polymerase chain reaction (PCR) followed by fluorescent in situ hybridisation for a limited number of chromosomes, later called 'preimplantation genetic diagnosis (PGD) version 1'. This review highlights the various molecular genetic techniques that have evolved to detect specific inherited monogenic disorders in the preimplantation embryo. Literature review in English was performed in PubMed from 1990 to 2021, using the term 'preimplantation genetic diagnosis'. With whole-genome amplification, multiple copies of embryonic DNA were created. This helped in avoiding misdiagnosis caused by allele dropout. Multiplex fluorescent PCR analysed informative short tandem repeats (STR) and detected mutations simultaneously on automated capillary electrophoresis sequencers by mini-sequencing. Comparative genomic hybridisation (CGH) and array CGH were used for 24 chromosome aneuploidy screening. Subsequently, aneuploidies were detected by next-generation sequencing using single-nucleotide polymorphism arrays, while STR markers were used for haplotyping. 'PGD version 2' included accurate marker-based diagnosis of most monogenic disorders and detection of aneuploidy of all chromosomes. Human leukocyte antigen matching of embryos has important implications in diagnosis and cure of haemoglobinopathies and immunodeficiencies in children by means of matched related haematopoietic stem cell transplantation from an unaffected 'saviour sibling' obtained by PGT.

Anti-Mullerian Hormone Levels in Indian Women Seeking Infertility Treatment: Are Indian Women Facing Early Ovarian Senescence?

BACKGROUND: Antimullerian hormone (AMH) is a key marker of ovarian reserve and predictor of response to fertility treatment. AIM: To understand the prevalence of low ovarian reserve in Indian women seeking infertility treatment, compare their AMH with age-matched fertile Indian controls and understand ethnic differences with Caucasian women. SETTING AND DESIGN: Retrospective observational study done as collaboration between our in vitro fertilization centre and a laboratory with Pan-India presence. MATERIALS AND METHODS: Women aged 20-44 years were selected as Group A (seeking infertility treatment n = 54,473), Group B (conceived naturally in the past; n = 283) and Group C (data of Caucasian women; n = 718). Serum AMH levels were measured and descriptive analysis done. STATISTICAL ANALYSIS: Descriptive statistics and Chi-square test. RESULTS: In Group A, 28.7%, 48.7% and 70.6% of women aged <30 years, 30-34 years and 35-39 years had serum AMH levels ≤2 ng/mL and the proportions were higher than Group B. The rate at which median AMH decreased was 1.1-2 times faster in Group B as compared to Group C. The decrease in median AMH across age groups in Group A was similar to Group B. CONCLUSIONS: Indian women in their late twenties and early thirties visiting fertility centers showed a worrisome trend of low AMH. Our study can be used as a reference for those women considering postponing pregnancy. It may be time to look at intangible cultural factors linked to social habits, ethnicity, diet, genetic predispositions, and environmental factors like endocrine disrupting chemicals contributing to premature ovarian senescence.

Hematological and Molecular Findings in the First Case of Hb J-Norfolk [HBA2: c.173G>A (or HBA1] in an Indian Patient.

We here report a case of a 23-year-old female from Mumbai, Maharashtra, India who was detected to carry the α chain variant Hb J-Norfolk [HBA2: c.173G>A (or HBA1]. She had no clinical symptoms and was referred to us for routine investigations and screening. An abnormal peak was detected on both high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) with a fast-moving band on cellulose acetate electrophoresis. There is no detailed study on the HPLC and CE pattern of this hemoglobin (Hb) variant, and therefore, this study will help in detecting and avoiding missing these variants during routine investigations and population screening. This is the first report of this variant in the Indian population.

Preimplantation Genetic Testing: Its Evolution, Where Are We Today?

Preimplantation genetic testing (PGT) is an early form of prenatal genetic diagnosis where abnormal embryos are identified, thereby allowing transfer of genetically normal embryos. This technology has become an integral part of Assisted Reproductive Technology (ART) procedures. Initial experiments with animals as early as 1890 and those in the mid and later part of the last century paved the forward path of ART and PGT. This review article covers the evolution of PGT and is a pointer toward current and fast-evolving technology, allowing scientists and doctors to better comprehend human reproduction, and ensure healthy pregnancy outcomes.

Detection of t(14;16)(q32;q22) and Monosomy 13 by FISH Analysis in a Patient with Multiple Myeloma Associated with Sjögren's Syndrome: The First Case Report from India.

Sjögren's syndrome (SS) is a chronic slowly progressive autoimmune disorder characterized by symptoms of oral and ocular dryness, exocrine dysfunction, and lymphocytic infiltration of exocrine glands. Multiple myeloma (MM) is a bone-marrow-based malignant neoplasm of plasma cells associated with serum/urine monoclonal paraproteins and lytic skeletal lesions. There have been very few reported cases of MM, who had SS as the first presentation. We report a case of a woman diagnosed with Sjögren's syndrome, who was later suspected to have multiple myeloma on serum protein electrophoresis. Fluorescence in situ hybridization (FISH) was carried out to check for deletions of loci 13q14.3, ATM, p53, and IGH (14q32) rearrangements on a bone marrow aspirate. Monosomy 13 was observed in 49% of cells, and a rearrangement at the IGH locus was seen in 42% of cells. To determine the partner chromosome associated with the IGH rearrangement, further FISH tests were set up for t(4;14)(p16;q32) followed by t(14;16)(q32;q22) on fresh slides. The test was negative for t(4;14) but positive for t(14;16) in 27% of cells. This confirmed the diagnosis of MM. We report the first case from India, having an association of Sjögren's syndrome with multiple myeloma, which showed t(14;16) and monosomy 13 by FISH analysis.

Identification and validation of candidate biomarkers involved in human ovarian autoimmunity.

Antibodies to multiple ovarian antigens have been proposed as markers of ovarian autoimmunity. The role of ovarian autoantibodies has been widely discussed in the pathophysiology of premature ovarian failure and unexplained infertility, but the autoantigens are yet to be identified. Three immunodominant ovarian autoantigens, α-actinin 4 (αACTN4), heat shock 70 protein 5 (HSPA5) and ß-actin (ACTB), have been identified using anti-ovarian antibody-positive sera from women with idiopathic premature ovarian failure (n=50) and women undergoing IVF (n=695), using mass spectrometry. These autoantigens were subsequently validated using Western blot, immunohistochemistry and enzyme-linked immunosorbent assay. These autoantigens are localized to different components of the ovary such as the ooplasm of the oocyte, theca, granulosa, corpus luteum and zona pellucida. All the above antigens were found to be expressed in the ooplasm throughout follicular development. All the autoantigens are expressed specifically in the oocyte except αACTN4. The three autoantigens could contribute to the array of biomarkers to be used for developing specific and sensitive tests for diagnosis of women at risk of premature ovarian failure and IVF failure due to ovarian autoimmunity and could give an insight into the molecular mechanisms involved in the pathophysiology of these conditions.

Can anti-ovarian antibody testing be useful in an IVF-ET clinic?

OBJECTIVE: To establish importance of anti-ovarian antibodies (AOA) testing in infertile women. DESIGN: A clinical reproductive outcome comparative study between two groups of women undergoing IVF-ET. Group 1 consists of women tested positive for AOA, put on corticosteroid therapy, reverted to AOA negative and then taken up for IVF-ET. Group 2 were seronegative for AOA. SETTING: Major urban infertility reference centre and National research institute. PATIENT(S): Five hundred seventy infertile women enrolled for IVF-ET. INTERVENTION(S): AOA testing, corticosteroid therapy and IVF-ET/ICSI. MAIN OUTCOME MEASURE(S): Comparable clinical outcome and significance of AOA testing established. RESULTS: AOA positive serum samples were sent periodically to re-investigate presence of AOA after corticosteroid therapy and women turned AOA negative were taken up for IVF-ET. Of the 70/138 women in group 1 who were treated with corticosteroids and turned seronegative for AOA, 22/70 were poor responders and needed donor oocyte-recipient cycles. Results demonstrated that fertilization and clinical pregnancy rates between both groups are comparable. Nevertheless, it is also observed that there is poor response to stimulation protocol, smaller number of oocytes retrieved and more spontaneous abortions in group 1 women. Hence not all outcomes following the treatment are comparable between the two groups. Usefulness of the test was established in two case studies. CONCLUSIONS: AOA testing could be included in the battery of tests investigating and treating infertility.

Epigenetic regulatory mechanisms associated with infertility.

Infertility is a complex human condition and is known to be caused by numerous factors including genetic alterations and abnormalities. Increasing evidence from studies has associated perturbed epigenetic mechanisms with spermatogenesis and infertility. However, there has been no consensus on whether one or a collective of these altered states is responsible for the onset of infertility. Epigenetic alterations involve changes in factors that regulate gene expression without altering the physical sequence of DNA. Understanding these altered epigenetic states at the genomic level along with higher order organisation of chromatin in genes associated with infertility and pericentromeric regions of chromosomes, particularly 9 and Y, could further identify causes of idiopathic infertility. Determining the association between DNA methylation, chromatin state, and noncoding RNAs with the phenotype could further determine what possible mechanisms are involved. This paper reviews certain mechanisms of epigenetic regulation with particular emphasis on their possible role in infertility.