Clinical Presentations and Semen Characteristics of Men Attending the Secondary Referral Infertility Clinic at Mumbai, India.

BACKGROUND: Limited information is available on the aetiology and semen profiles of male infertility in Indian population. AIM: The aim of this study is to study the clinical and semen characteristics of men attending the infertility clinic and also to understand the impact of World Health Organization (WHO) 2010 reference values on the diagnosis of male infertility. SETTING AND DESIGN: A retrospective study evaluating the medical case records (January 2005 to December 2015, [n = 1906]) of men attending infertility clinic in Mumbai, India. MATERIALS AND METHODS: The aetiology was classified based on the andrology evaluation and other investigations. Semen profiles were compared during the years 2005-2010 and 2011-2015 using WHO 1999 and WHO 2010 criteria, respectively. STATISTICAL ANALYSIS: The Chi-square and Mann-Whitney U tests were performed using Open Source Epidemiological software and Social science calculators. RESULTS: The aetiology of male infertility was determined in 62% of the men; while the cause remained undetermined in 38%. Varicocele (25%), urogenital infections (10%), sexual dysfunctions (8%) and vas aplasia (8%) were identified as major aetiologies in our cohort. Men with sexual dysfunctions and vas aplasia were significantly higher during the years 2011-2015 as compared to 2005-2010. Men having normozoospermia (10%) and azoospermia (3%) were increased, whereas those having oligoasthenozoospermia (17%) were reduced in 2011-2015 as compared to 2005-2010. According to WHO 1999 criteria , 12-15% of men showed abnormal semen profiles. The semen parameters of these men became normal on using WHO 2010 reference values. CONCLUSIONS: Varicocele is the most common aetiology in infertile men. Idiopathic infertility was seen in a higher proportion among the infertile men.

Follicle stimulating hormone receptor gene variants in women with primary and secondary amenorrhea.

PURPOSE: This retrospective study was designed to analyze the FSHR gene variants in subjects with primary and secondary amenorrhea with hypergonadotropic hypogonadism. MATERIALS AND METHODS: Eighty six women with primary or secondary amenorrhea and 100 normally cycling proven fertile women of Indian origin were retrospectively studied. These subjects were systematically screened for entire FSHR gene. RESULTS: The frequency distribution of polymorphism at -29 position of FSHR gene is altered in women with primary and secondary amenorrhea as compared to controls. AA genotype at -29 position of FSHR gene seems to be associated with increased serum FSH levels in the study subjects. We have identified a novel homozygous mutation C(1723)T (Ala(575)Val) in one woman with primary amenorrhea. CONCLUSIONS: Our findings suggest that increased serum FSH levels in subjects with primary amenorrhea correlated to FSHR genotype at position -29. We identified a novel homozygous mutation C(1723)T (Ala(575)Val) in a woman with primary amenorrhea.

Specific and sensitive immunoassays detect multiple anti-ovarian antibodies in women with infertility.

Serum anti-ovarian antibodies (AOAs) have been shown in autoimmune premature ovarian failure and in vitro fertilization-embryo transfer (IVF-ET) cases. The specificity of assays detecting these antibodies has been questioned. Researchers have used several techniques (e.g., ELISA and indirect immunofluorescence). Few have reported on the non-specificity and the type of molecular and cellular targets. We reported earlier on the presence of naturally occurring anti-albumin antibodies as the likely factor for non-specificity. Having developed a novel blocking recipe, we show substantial elimination of this non-specificity. With these standardized tests, we hereby report multiple targets at protein and histological levels. In our study group, 15 of 50 (30%) patients with premature ovarian failure and 13 of 50 (26%) IVF-ET patients showed the presence of AOAs. Western blotting showed a large number of patients making AOAs to a 90-kDa protein, followed by 97- and 120-kDa proteins. Histochemically, it was evident that the sera of these patients predominantly react with the oocyte; other somatic cellular targets are also involved. The specific non-invasive test developed by us was found to be useful because it could carry out a reliable diagnosis of an autoimmune etiology that would be very helpful to select patients in whom immune-modulating therapy could be recommended, which in turn may restore ovarian function and fertility.

Introital swab testing for Chlamydia trachomatis in a resource-poor setting: an Indian perspective.

OBJECTIVE: Chlamydia trachomatis (CT) is implicated both in tubal infertility and in cervical dysplasia. Early detection of this infection is uncommon due to its asymptomatic nature and to lack of adequate health care facilities, leading to irreversible sequelae. This study evaluates the use of an introital specimen from women attending the Institute's infertility clinic to detect CT by polymerase chain reaction (PCR) and to correlate it with intraepithelial changes (IEC) of the cervix by Pap smears. METHODS: Introital and endocervical swab specimens were taken from 100 infertile women for PCR. An endocervical smear was taken for Pap staining. RESULTS: The CT infection rate was 34%. Sensitivity of introital and endocervical specimens for detection of CT was 82.4% and 85.3%, respectively (P > 0.05); both had 100% specificity. Sixty-seven percent of infected women were less than 30 years of age and only 15% of these reported discharge. Vaginitis/cervicitis was observed in 35% of the positive cases. IEC suggesting inflammation was seen in 74% of the infected women, as compared to 48% of subjects with normal cytology (p = 0.016). Being noninvasive, self collection of an introital specimen can be advocated in large-scale settings in our country for detection of CT in order to contain the infection and its complications.

Endometrial expression of immunomodulatory cytokines and their regulators during early pregnancy in bonnet monkeys (Macaca radiata).

BACKGROUND: It is well established that endometrium undergoes extensive histological changes during implantation and subsequent stages of pregnancy in rodents as well as primates. Our previous investigation using a non-human primate model has demonstrated that morphological alterations are initiated even before the embryo invades the endometrium. The present study was undertaken to determine whether the embryo-induced morphological changes are accompanied by any alteration in the protein levels of the immunomodulatory cytokines and their regulators in the preimplantation stage endometrium. METHODS: The endometrial expression of immunosuppressive factors such as transforming growth factor beta2 (TGFbeta2), glycodelin (PP14), leukaemia inhibitory factor (LIF) and interleukin-6 (IL-6) were analysed on day 6 post-ovulation in pregnant and non-pregnant bonnet monkeys (Macaca radiata) using immunohistochemical methods. RESULTS: The endometrial expression of TGFbeta2, TGFbeta2 receptor, PP14 and IL-6 were significantly up-regulated (p < 0.05) in pregnant animals as compared to non-pregnant animals, whereas the expression of LIF and its receptor remained unaltered in pregnant animals. CONCLUSIONS: Expression levels of some immunomodulatory cytokines in endometrium are significantly increased even before the embryo invades the endometrium. The altered cytokine expression profile in endometrium probably contributes towards generating a conducive environment for the embryo survival, growth and development in the uterus.

Circulating auto-antibodies against the zona pellucida and thyroid microsomal antigen in women with premature ovarian failure.

Premature ovarian failure (POF) is a disorder of multicausal etiology leading to infertility in women. Development of ovarian auto-antibodies is a causative factor in most POF cases, but no consensus on the ovarian antigenic determinants has been reached till date. In the present study, sera from 15 POF cases, seven normally cycling women and eight menopausal women were studied by immunohistochemistry (IHC) for the presence of anti-ovarian antibodies. 10 of the 15 POF sera (66.6%) presented with anti-ovarian antibodies (Ao). Of these, two demonstrated antibodies to the zona pellucida (ZP) as well as strong immunoreactivity to granulosa cells (Azg), while the remaining eight exhibited anti-ZP antibodies with negligible staining in granulosa cells (Az). The antibodies showed cross-reactivity with ZP from various species such as human, sheep, marmoset, pig and mouse. Among various murine tissues, the antibodies cross-reacted only with thyroid and not with uterus, spleen, kidney, liver, adrenal, pancreas and pituitary. Five of the eight Az individuals presented with significant titres of anti-thyroid antibodies (Azt). In the control group, one menopausal control presented with reactivity to both ZP and GC, the autoimmunity possibly being a consequence of surgical trauma; while one normally cycling woman tested positive for anti-thyroid antibodies. The IHC results were confirmed by ELISA using heat-solubilized isolated ZP (SIZP) as the antigen. Out of seven Ao samples assessed by ELISA, five reacted with SIZP. Preincubation of these five samples with varying concentrations of SIZP demonstrated a dose-dependent decrease in reactivity in ELISA and abolished staining in IHC, confirming the specificity of auto-antibodies to ZP in the POF group. Our results thus suggest that ZP is an important ovarian antigen in autoimmune POF.