Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions.

PURPOSE: The purpose of this study was to determine the association of AZFc subdeletions (gr/gr, b1/b3 and b2/b3) and deletion of DAZ and CDY1 gene copies with male infertility METHODS: Three hundred twelve controls, 172 azoospermic and 343 oligozoospermic subjects were subjected to AZFc subdeletion typing by STS PCR. Deletion of DAZ and CDY1 gene copies was done using sequence family variant analysis. Sperm concentration and motility were compared between men with and without AZFc subdeletions. Effect of the AZFc subdeletions on ICSI outcome was evaluated. RESULTS: Amongst the three AZFc subdeletions, the frequency of gr/gr was higher in oligozoospermic (10.5 %) and azoospermic (11.6 %) men as compared to controls (5.1 %). In men with AZFc subdeltions, loss of two DAZ and one CDY1 gene copy made them highly susceptible to azoospermia and severe oligozoospermia with OR of 29.7 and 26, respectively. These subdeletions had no effect on ICSI outcome, albeit there were an increased number of poor quality embryos in AZFc subdeleted group. CONCLUSION: AZFc subdeletions are a major risk factor for male infertility in the Indian population. In the subjects with AZFc subdeletions, the deletion of DAZ and CDY1 gene copies increases its susceptibility to azoospermia or severe oligozoospermia. Since these deletions can be vertically transmitted to the future male offspring by ICSI, it will be essential to counsel the couples for the transmission of the genetic defect in the male offspring born after assisted reproduction and the risk of perpetuating infertility in future generation.

Dyslipidemia with particular regard to apolipoprotein profile in association with polycystic ovary syndrome: a study among Indian women.

OBJECTIVE: To investigate putative dyslipidemia in women with polycystic ovary syndrome (PCOS) with particular emphasis on specific parameters of atherosclerotic risk, and to assess the independent influence of obesity and hyperandrogenemia on these parameters. SUBJECTS: Women investigated were among those attending the infertility clinics. Three groups of women were studied: (I) a core study group consisting of oligomenorrhoeic, chronically anovulatory women with or without obesity in whom polycystic ovaries were confirmed through ultrasound evidence, and were established to be the cause of infertility; II) a control group of non-hirsute, non-obese women with regular menstrual cycles; and (III) a group of controls consisting of women with obesity, but with normal ovarian morphology and regular menstrual cycles. METHODS: All three study groups were investigated for androgen (total testosterone) and lipid-lipoprotein profile, including apolipoproteins, ApoA1 and ApoB. Retrospective analysis of the data was carried out to assess hyperandrogenism in the study group of women with PCOS as well as to investigate changes in the lipid-lipoprotein profile, particularly the measures of cardiovascular risk, ApoA1 and ApoB. RESULTS: Triglycerides showed a significant increase in the PCOS group compared to controls, whereas HDL-cholesterol as well as HDL-carrying ApoA1 showed a significant decrease (P < .05). Also a significant finding was the decrease in ApoA1/ApoB ratio among the women with PCOS compared to both controls and obese women. A direct negative correlation of this decrease in ApoA1/ApoB ratio with the Body Mass Index was also confirmed in the study. Hyperandrogenemia in terms of significantly raised total testosterone levels was found in 30% of the PCOS women. However, no direct correlation of this increase with changes in lipid-lipoprotein profile could be observed. CONCLUSION: The study confirms the trend toward dyslipidemia among women with PCOS, particularly in parameters associated with cardiovascular risk. A significant association of obesity rather than raised testosterone with this dyslipidemia was also confirmed by the study.

Chlamydia trachomatis infection among asymptomatic males in an infertility clinic.

Chlamydia trachomatis can lead to a variety of complications including tubal infertility. Similarly asymptomatic infection in male partner can also hinder conception. The prevalence of this infection among the infertile female in the Institute's Infertility Clinic was observed to be 34%. Hence the present study was undertaken to find out these infection among the asymptomatic male partners of these infected women. Fifteen asymptomatic males who were not treated with any antibiotics in recent past were enrolled. First voided urine, semen and blood were collected from each individual for diagnosis of this infection. Chlamydia antigen was detected in 33.3% while Chlamydia antibody was detected in seven (46.7%) of these cases. Of these seven, three cases were positive for antigen. This preliminary observation suggests that amongst the infertile couple a sizable percentage (60%) of asymptomatic male partners remain infected with Chlamydia trachomatis.

Poor quality of sperm as it affects repeated early pregnancy loss.

A study was carried out to determine whether males contribute to repeated early pregnancy loss. Semen samples were analyzed from proven-fertile men (n = 51 group I) and from men whose partners presented with early pregnancy loss (>3 first trimester abortions, n = 32 group II). Routine analysis, sperm function tests, and ultrastructural studies of sperms were carried out. Female factor could be identified in 25 (78%) couples, and in 7 (22%) no cause either male or female could be identified and the semen analysis was normal. Percent morphologically normal did not differ significantly between the groups, but increased sperm head abnormalities were seen. The functional tests were all normal except for a significant decrease in the capacity of nuclear chromatin to decondense in vitro. The ultrastructural studies showed defects of chromatin condensation and irregular nuclei with vacuoles. This study points to the loss of chromatin integrity as a possible contributing factor from males to early pregnancy loss.

Resazurin reduction test to evaluate semen quality.

The resazurin test (REZ TEST) was performed on semen samples obtained from 75 untreated subfertile and 10 pregnancy confirmed fertile males. The results were compared with other sperm parameters to assess the quality of semen. The highest correlation of REZ grade was with motile sperm (r = 0.90, P < 0.001), sperm viability (r = 0.80, P < 0.001) and sperm concentration (r = 0.71, P < 0.001). The REZ grade indicated significant difference in the rate of positive tests between samples from fertile males and patients exhibiting abnormal semen parameters. The RES TEST had a positive predictive value of 93.75% for a progressives motile sperm concentration of > 20 x 106/ml and a negative predictive power of 88.7% for the same variable at a criterion value of 10 x 106/ml. It is suggested that REZ TEST can be performed with a relatively small volume of semen, it is easy to perform and requires no technical equipments.

Early pregnancy factor (EPF) as a marker for detecting subclinical embryonic loss in clomiphene citrate-treated women.

PROBLEM: A discrepancy exists between the apparently normal ovulation and the pregnancy rates in women treated with clomiphene citrate (CC). Our previous studies have indicated that immuno-suppressive "early pregnancy factor" (EPF) is a novel marker to detect subclinical embryonic loss in infertile women. METHOD: In the present study EPF was used as a marker to detect subclinical embryonic loss in women treated with CC with/without gonadotropins. In some of the women treated with CC, conception was assisted by artificial insemination with husband's semen (AIH). RESULTS: Our results have indicated that fertilization occurred (EPF + ve) in 47.7% (52/109) of women treated with CC with/without gonadotropins; 13.46% (7/52) retained the fetus and continued pregnancy till full term, whereas 78.9% (41/52) did not retain the fetuses. In the group where after stimulation, conception was assisted by AIH, fertilization was observed in 38.24% (26/68), retention in 11.54% (3/26) but subclinical embryonic loss was observed in 80.8% (21/26) cases. CONCLUSION: Thus, our results have indicated that subclinical embryonic loss may account for some of the discrepancy observed between the apparently normal ovulation and the pregnancy rates in women treated with clomiphene citrate.

Lipoprotein lipids in androgen excess--a study among Indian women.

OBJECTIVE: To assess changes in lipoprotein-lipid profile vis-a-vis putative risk of atherosclerotic diseases, among a group of hyperandrogenic women. SUBJECTS AND METHODS: Women studied were among those being screened for polycystic ovarian disease (PCOD) at the Reproductive Endocrinology Clinic of the institute. They all had oligomenorrhea/chronic anovulation as their problem and had clinical or laboratory evidence of hyperandrogenism, viz., hirsutism or elevated serum testosterone levels. Lipoprotein-lipid profiles obtained in 51 such women were compared with those of 11 controls with normal menstrual cycles and no evidence of hyperandrogenism. RESULTS: No significant changes were observed in any of the lipoprotein-lipid variables which could be attributed to hyperandrogenism per se. However, a combined effect of obesity and raised circulating androgens in causing a significant change in the lipoprotein-lipid profile (increased cholesterol, LDL-C/HDL-C, and cholesterol/HDL-C) was clearly discernible from the study. CONCLUSIONS: Hyperandrogenism by itself may not signal a risk for atherosclerotic diseases. However, the potential of such risk would be significantly enhanced if obesity is associated with high circulating levels of androgens.

Serum progesterone and norethisterone levels following injection of norethisterone enanthate in different sites and doses.

Serum progesterone (P) and norethisterone (NET) levels following injection of norethisterone enanthate (NETEN) were studied in 11 regularly menstruating women. In 6 subjects 200 mg NETEN was administered to the gluteal (IG) or deltoid (ID) region sequentially. The serum P levels remained anovulatory (less than 4 ng/mL) up to 12 weeks. Serum NET levels were similar whether injection was given IG or ID (paired t - test, NS). In 5 subjects given a 150-mg dose, serum P levels remained anovulatory up to 11 weeks. Serum NET levels declined faster than with the 200-mg dose, but the difference was not significant (Student's t - test, NS). Wide inter-subject variations were seen in both groups. NETEN therefore can effectively be administered in gluteal or deltoid regions. A lower dose of 150 mg may have contraceptive potential on an 8-week schedule.

Actinomyces in cervical smears of women using intrauterine contraceptive devices.

Cervical smears from 1,784 women who attended the family planning clinics of the Institute for Research in Reproduction were examined for the presence of Actinomyces-like organisms. Among 815 intrauterine contraceptive device (IUD) users, the repeat smears from 57 women were positive for Actinomyces-like organisms, giving a prevalence rate of 6.99%. Immunofluorescent staining using specific antisera confirmed the presence of A. israelii in all 57 women. Forty IUD users whose smears were positive for Actinomyces-like organisms underwent bacteriologic culture studies; A. israelii was isolated in 23 of these cases. The clinical findings at the time of smear collection in the 57 IUD users were within normal limits. The initial cervical smears of all IUD users and both the initial and repeat smears of all nonusers were negative for Actinomyces-like organisms. The data indicate that prolonged use (greater than 2 years) of an inert or copper intrauterine device promotes the overgrowth of Actinomyces in the vagina and that this can be detected by routine cervical cytology.

PIP: Cervical smears from 1784 women who attended a family planning clinic in India were examined for the presence of Actinomyces-like organisms. There were 57 (7%) positive smears among the 815 IUD users in this group. Bacteriologic culture studies were carried out in 40 of these women and Actinomyces israelii was isolated in 23 cases. The initial cervical smears of all IUD users and both the initial and repeat smears of all nonusers were negative for Actinomyces. None of the positive smears involved women with less than 1 year of IUD use and only 4 cases were positive with 1-2 years of IUD use. There was no association between the presence of Actinomyces-like organisms and type of IUD, however. The cervical and pelvic examination findings in the 57 women with positive Actinomyces smears were within normal limits at the time of smear collection. These findings suggest that longterm IUD use promotes the outgrowth of Actinomyces in the vagina. Routine cervical cytology and clinical observation are recommended for the early detection of possible pelvic inflammatory disease in these women.

Salivary antipyrine half-life during injectable progestagen contraception.

Antipyrine pharmacokinetics were studied in 6 healthy women before and 2, 8 and 12 weeks after administering the injectable progestagen (progestin), norethisterone (norethindrone) enanthate 200mg intramuscularly. Additionally, antipyrine kinetics in 5 women who had previously used the injectable contraceptive for 8 to 14 months were compared with values obtained in 14 non-users. Antipyrine was measured in saliva using a spectrophotometric method, following an oral dose of 18 mg/kg bodyweight. In the 6 women studied prospectively the mean salivary antipyrine half-life was 14.91 +/- 1.5 hours (SEM) before administering the injection, and 13.56 +/- 0.73 at 2 weeks, 15.13 +/- 1.86 at 8 weeks and 15.21 +/- 2.46 hours at 12 weeks after the injection. The mean antipyrine half-life in the 5 long term users of injectable progestagen was 14.21 +/- 2.53 hours compared with 13.66 +/- 0.98 hours in non-users. The results of this study suggest that - in contrast to published data on combined oral contraceptives - neither short nor long term use of parenteral norethisterone enanthate in Indian women is associated with significant alterations in antipyrine clearance.