Joint IFS-ISAR-ACE Recommendations on Resuming/Opening up Assisted Reproductive Technology Services.

COVID-19 - A Global challenge on a scale not previously seen. Reproductive care is essential for the well-being of society and therefore the treatment needs to be completely re-thought and individualised. Infectivity and mortality rates are higher than previous pandemics and the disease is present in almost every country. Propagation and containment have varied widely by location and, at present, the timeline to complete resolution is unknown. With successful mitigation strategies in some areas and emergence of additional data, the societies have sanctioned gradual and judicious resumption of delivery of full reproductive care. When we resume, monitor local conditions, including prevalence of disease, status of government or state regulations, and availability of resource. It is important to implement proactive risk assessment within their practices prior to restarting services. One needs to develop clear and modified plans to ensure the ability to provide care while maximizing the safety of their patients and staff. One should also remain informed and stay current regarding new medical findings. These recommendations provide resources for restarting ART practice again.

Niche role of MRI in the evaluation of female infertility.

Infertility is a major social and clinical problem affecting 13-15% of couples worldwide. The pelvic causes of female infertility are categorized as ovarian disorders, tubal, peritubal disorders, and uterine disorders. Appropriate selection of an imaging modality is essential to accurately diagnose the aetiology of infertlity, since the imaging diagnosis directs the appropriate treatment to be instituted. Imaging evaluation begins with hystero- salpingography (HSG), to evaluate fallopian tube patency. Uterine filling defects and contour abnormalities may be discovered at HSG but usually require further characterization with pelvic ultrasound (US), sono-hysterography (syn: hystero-sonography/saline infusion sonography) or pelvic magnetic resonance imaging (MRI), when US remains inconclusive. The major limitation of hysterographic US, is its inability to visualize extraluminal pathologies, which are better evaluated by pelvic US and MRI. Although pelvic US is a valuable modality in diagnosing entities comprising the garden variety, however, extensive pelvic inflammatory disease, complex tubo-ovarian pathologies, deep-seated endometriosis deposits with its related complications, Mulllerian duct anomalies, uterine synechiae and adenomyosis, often remain unresolved by both transabdominal and transvaginal US. Thus, MRI comes to the rescue and has a niche role in resolving complex adnexal masses, endometriosis, and Mullerian duct anomalies with greater ease. This is a review, based on the authors' experience at tertiary care teaching hospitals and aims to provide an imaging approach towards the abnormalities which are not definitively diagnosed by ultrasound alone.

Role of Gene Xpert in the Detection of Genital Tuberculosis in Endometrial Tissue among Women with Infertility.

OBJECTIVE: The objective of the study is to evaluate the clinical utility of Gene Xpert compared with other available diagnostic modalities in prompt diagnosis of female genital tuberculosis (TB) causing infertility. MATERIAL AND METHODS: This was a prospective, cross-sectional analytical study. Premenstrual endometrial biopsy specimens were collected from 176 infertile women of reproductive age group suspected of having genital TB. Samples were processed for acid-fast bacilli, culture, histopathology, polymerase chain reaction (PCR), and Gene Xpert. Patients detected positive on Gene Xpert and PCR were subjected to laparoscopy to look for affirmative findings of genital TB. The results were analyzed using composite gold standard consisting of patients positive with culture, histopathology, and laparoscopy. RESULTS: A total of 18 patients were found positive using composite gold standard. Laparoscopy was positive in 15 patients, whereas culture and histopathology were positive in three and two patients, respectively. Gene Xpert was positive in two patients. None of them was detected with rifampicin resistance. The sensitivity of Gene Xpert was 11.11% whereas the specificity was 100%. CONCLUSION: Since genital TB is a paucibacillary disease, multiple diagnostic modalities are needed for diagnosis. Gene Xpert appears to be a useful modality in diagnosis of genital TB, owing to its high specificity, and can be recommended in conditions where microscopy, culture, and histopathology are negative; however, further randomized studies are required to support our hypothesis.

Primary Adenocarcinoma of the Fallopian Tube: A Rare Entity.

Primary fallopian tube carcinoma is an uncommon gynaecologic malignancy usually seen in postmenopausal females. We present a case of a 66-year-old postmenopausal female who presented with complaint of blood mixed vaginal discharge on and off for past one month. Workup of the patient revealed no abnormality other than presence of atypical squamous cells on Papanicolaou (PAP) smear. MRI showed mildly bulky cervix with around 4cc fluid in endometrial cavity. As the patient remained symptomatic and fluid in endometrial cavity persisted, total abdominal hysterectomy with bilateral salpingo-oophorectomy was done. On histopathological examination, fimbrial end of left tube had features of poorly differentiated papillary serous adenocarcinoma. Postoperatively, she was given chemotherapy and is doing well with more than 3 years of follow up. This case highlights the importance of high suspicion in postmenopausal women with bleeding per vaginum, where there is little to suggest clinically or radiologically.

The Relationship Between Uterine Artery two-dimensional Color Doppler Measurement and Pregnancy Outcome: A Prospective Observational Study.

BACKGROUND: The purpose of the study was to evaluate the role of uterine blood flow parameters measured by uterine artery two-dimensional (2D)-power color doppler (PCD) ultrasound in predicting fertility outcomes in women undergoing IVF-ET cycles. METHODS: In this prospective observational study, a total of 188 infertile women who underwent IVF-ET cycles were investigated. Uterine artery 2D-PD measurements were taken during early follicular phase and on day of trigger. Pulsatility Index (PI), Resistant Index (RI), Peak Systolic Velocity (PSV), and Systolic/Diastolic ratio (S/D) were measured. Statistical correlation was sought between the doppler parameters and fertility outcomes. RESULTS: The pregnancy rate was 40.43% (76/188). The women who conceived (n= 76) (Group A) were found to have mean age of 31.2±3.9 years whereas the non-pregnant group of women (n=112) (Group B) had mean age of 31.45±4.25 years. The mean PI measurements subsequently during early follicular phase and on the day of hCG trigger between group A and group B were comparable (2.09±1.15 versus 1.9±0.95; p=0.385 and 1.86±1.12 versus 2.03±1.0; p=0.192, respectively). No significant changes in the uterine artery PSV values and S/D values and RI were noted during the cycle. CONCLUSION: Uterine artery doppler evaluation in women undergoing IVF cycles was not predictive of the pregnancy outcomes.

Impact of maternal nutrition in hepatitis E infection in pregnancy.

BACKGROUND AND AIM: The basis of host response in hepatitis E virus (HEV)-related liver disease during pregnancy-is still unclear. The study aims to evaluate anthropometric parameters and biochemical nutritional parameters in hepatitis E infection during pregnancy and correlate it with severity of the disease. METHODS: A total of consecutive 267 pregnant women with jaundice were recruited. The jaundiced patients were classified as acute viral hepatitis (AVH) or acute liver failure (ALF). The study group included 144 pregnant women with HEV infection and 144 healthy asymptomatic age and gestational age-matched pregnant women as controls. Nutritional factors were evaluated on basis of anthropometric parameters and biochemical factors. Serum prealbumin and folate were assayed by ELISA kit. RESULTS: All nutritional parameters were significantly lower in pregnant women with HEV infection as compared with healthy pregnant controls. Some of the nutritional parameters significantly lower in ALF pregnant patients compared to AVH pregnant patients in HEV group. Linear regression analysis of the AVH group showed that serum total protein and mid-upper arm circumference (MUAC) were significant predictors for bilirubin, body mass index (BMI) could significantly predict viral load level, and total protein, prealbumin, folate, and tricep skin fold thickness (TSFT) could significantly predict prothrombin time. In ALF group, serum prealbumin could significantly predict bilirubin levels and MUAC could significantly predict prothrombin time. CONCLUSION: Malnutrition might confer a higher predisposition for HEV infection during pregnancy and is associated with increased severity of disease in terms of occurrence of ALF.

Entropy vs standard clinical monitoring using total intravenous anesthesia during transvaginal oocyte retrieval in patients for in vitro fertilization.

STUDY OBJECTIVE: Day care surgery is an important arena for monitors of anesthetic depth where minimizing drug use is essential for rapid turnover. Underdosage, on the other hand, carries the risks of intraoperative awareness and pain. Transvaginal oocyte retrieval (TVOR), often performed under total intravenous anesthesia using propofol and fentanyl in Indian patients, is a procedure of special interest because, in addition to the above concerns, toxic effects of propofol on oocytes have been described. We have studied the role of entropy monitor, a depth of anesthesia monitor, in optomising drug titration and facilitating distinction between analgesic and hypnotic components of anesthesia. DESIGN: Prospective randomized controlled study. SETTING: Operating theater and postoperative recovery area. PATIENTS: One hundred twenty American Society of Anesthesiologists class I and II female patients coming to the IVF centre for TVOR under total intravenous anesthesia using propofol and fentanyl. They were randomly allocated into 2 groups: Group EM (drugs titrated as per entropy values: state entropy and response entropy) and group CM (drugs titrated as per standard clinical monitoring). INTERVENTION: None. MEASUREMENTS: Total propofol consumption (TP), total fentanyl consumption (TF), on-table recovery time (T1), time to discharge (T2), intraoperative awareness (A). MAIN RESULTS: Patients in group EM demonstrated 6.7% lesser consumption of propofol (P= .01), 10.9% more consumption of fentanyl (P= .007) and 1 minute faster recovery on-table (P= .009) as compared to group CM. In the PACU, only 10% patients of group EM required supplemental analgesia as opposed to 28.3% in CM group (P= .01). Time to discharge was similar in both groups and no intraoperative awareness was noted. CONCLUSION: Entropy monitor is a useful tool allowing distinction between analgesic and hypnotic components of general anesthesia in patients undergoing TVOR and facilitating drug titration accordingly. Its impact on intraoperative awareness needs to be further evaluated.

Effect of CYP1A1 gene polymorphism and psychological distress on seminal analysis parameters.

BACKGROUND: Psychological factor alters fertility hormones and contributes to male infertility. Anxiety and depression are common manifestations of psychological distress. Cytochrome P-4501A1 (CYP1A1) metabolizes xenobiotics and fertility hormones that influence male fertility. The effect of CYP1A1 polymorphism on male fertility has remained controversial. The present study was designed to assess the effect of psychological distress and CYP1A1 polymorphisms and their interactions on parameters of seminal analysis. METHODS: Eighty male partners of infertile couples were evaluated for level of distress using Hospital anxiety and depression score (HADS) questionnaire. As per WHO guidelines (2010), sperm count, motility and morphology were assessed and subjects were classified as (a) subjects having normal sperm characteristics and (b) subjects having abnormal sperm characteristics. CYP1A1 polymorphisms were detected by ASO-PCR. RESULTS: The significant odd's ratio indicates that psychological distress (OR:10.54; CI:3.72-29.84; P < 0.001), CYP1A1*4(OR:10.31; CI:3.01-35.24; P < 0.001) and CYP1A1*2C (OR:7.01; CI:1.78-27.56; P = 0.002) polymorphisms are risk factors for the development of abnormal sperm characteristics in male subjects. Data analysis with two way ANOVA shows that psychological distress, CYP1A1*4 and CYP1A1*2C polymorphisms significantly affect but do not interact among them to influence sperm parameters. CONCLUSIONS: It is concluded that CYP1A1 gene polymorphisms and psychological distress act independently but do not interact with each other in pathogenesis of male infertility.

Current Scenario of Vitamin D Status During Pregnancy in North Indian Population.

PURPOSE OF THE STUDY: The aim of the study was to determine the prevalence and risk factor for vitamin D deficiency in our pregnant population. METHOD: A total of 418 healthy primigravida with single live pregnancy and sure of dates attending the antenatal clinic between October 2011 and April 2013 were recruited. Women were excluded if they had history of current or past chronic medical disease. Women were also excluded if they had history of medication with drugs interfering with calcium and vitamin D metabolism. RESULTS: The prevalence of vitamin D deficiency during pregnancy has been found to be 391 (93.5 %). Severe vitamin D deficiency among pregnant patients was 34.44 % (144/418). The levels of serum 25(OH)D and serum calcium were significantly lower in severe deficient group than the adequate group [7.10 ± 1.49 vs. 38.90 ± 4.22 ng/ml (p = 0.001) and 7.13 ± 1.41 vs. 9.39 ± 0.88 ng/ml (p = 0.001)], respectively. Maternal education, husband education, socioeconomic status, serum calcium, serum phosphorous, and season were significant factors associated with vitamin D deficiency. Significant independent variables for severe vitamin D deficiency were low serum calcium, serum alkaline phosphatase, and serum phosphorus (OR 39.41, 95 % CI 10.30-150.85, p < 0.01), (OR 18.03, 95 % CI 3.95-82.44, p < 0.01), and (OR 8.40, 95 % CI 2.47-28.61, p < 0.01). CONCLUSION: Vitamin D deficiency is highly prevalent among pregnant women in Northern India, and these raises concern about the health consequences for the mother and the offspring.

Reduced glutathione in hepatitis E infection and pregnancy outcome.

AIM: To study reduced glutathione (GSH) as a marker of oxidative stress in hepatitis E virus (HEV) infection during pregnancy, and to clarify its association with pregnancy outcome. METHODS: A total of 30 pregnant and 30 non-pregnant women with HEV infection were enrolled in the present study, along with 30 age- and gestation-matched healthy pregnant controls. Serum GSH was measured using commercially available enzyme-linked immunoassay kit. RESULTS: Significantly lower GSH was observed in HEV-infected pregnant women than in healthy pregnant controls (10.44 ng/mL vs 19.77 ng/mL; P < 0.01). No significant association was observed between GSH and pregnant women and non-pregnant women with HEV infection (P = 0.54). Serum GSH ≤10.88 ng/mL was more likely to be associated with HEV infection during pregnancy, with sensitivity and specificity of 73.3%. Lower GSH was observed in pregnant women with HEV infection having preterm delivery and low birthweight newborns compared with healthy pregnant women (P < 0.01 and P < 0.05, respectively). Serum GSH was lower in pregnant women with HEV infection who had stillbirth compared with those having live births (7.21 ng/mL vs 6.12 ng/mL, P = 0.60). CONCLUSION: Oxidative stress is present in HEV infection during pregnancy, as shown by low GSH, and is associated with adverse pregnancy outcomes. Serum GSH ≤10.88 ng/mL during pregnancy can be used for risk stratification for HEV infection.

RETRACTED: Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the ASRM Publications Committee. The Committee reviewed concerns related to the accuracy of data reported in Table 2 and the authors acknowledged significant errors that could not be corrected because they were unable to provide the original data. As the Committee cannot vouch for the accuracy of the data, we have issued a retraction of this article.

Estradiol Level on Day 2 and Day of Trigger: A Potential Predictor of the IVF-ET Success.

OBJECTIVE: To evaluate role of serum estradiol levels in predicting likelihood of pregnancy in women undergoing GnRH-a protocol in IVF-ET cycles. DESIGN: A 3-year retrospective analysis of estradiol levels on down-regulated day 2, day 6, and day of hCG trigger and subsequent clinical pregnancy rates. SETTING: A university hospital tertiary referral centre. POPULATION OR SAMPLE: Women undergoing IVF treatment. METHODS: Hormonal assessment on the down-regulated day 2, day 6, and day of hCG trigger. MAIN OUTCOME MEASURES: Comparison of hormonal profile, antral follicular count on day 2, endometrial thickness on day of trigger, and number of oocytes retrieved between pregnant and the non-pregnant group. The prediction of IVF success was based on the quantitative levels of estradiol on a specific day in down-regulated cycle. RESULTS: The overall pregnancy rate was 32.25 % (50/160). Estradiol level on down-regulated day 2 was 31.9 ± 12.6 and on the day of trigger was 1,996.46 ± 1,252.36 in pregnant women, which was significantly higher as compared to estradiol levels in non-pregnant women (27.6 ± 12.3 and 1,525.1 ± 1,116.42, respectively). It was found to be a significant prognostic marker for successful IVF treatment. Estradiol levels on down-regulated day 6 were found to be non-significant between the two groups. CONCLUSIONS: Estradiol level on down-regulated day 2 of menstrual cycle and on the day of trigger was found to have a significant impact on the success of IVF-ET.

Role of cytokines in development of pre-eclampsia associated with periodontal disease - Cohort Study.

AIM: The present study was designed to find any association of cytokines in women with periodontal disease and development of pre-eclampsia in North Indian population. MATERIALS AND METHODS: A total of 504 consecutively registered primigravida with a single live pregnancy were recruited at 14-18 weeks of gestation from antenatal clinic of Maulana Azad Medical College & associated Lok Nayak Hospital and Maulana Azad Institute of Dental Sciences, New Delhi. One periodontist performed oral health examination of all patients at inclusion into study. Blood samples were collected to measure the level of cytokines IL-4, IL-10, TNF-α and IFN-γ. RESULTS: The profile of blood levels of cytokines from women with periodontal disease was observed. The log serum levels of TNF-α & IL-4 at 16-18 weeks of gestation were significantly higher in women with periodontal disease (4.13 ± 2.06; 0.47 ± 1.56 pg/ml respectively) than in women with healthy gums (2.16 ± 1.51; 0.02 ± 1.84 pg/ml respectively, p < 0.001). Periodontal disease is associated with log serum TNF-α levels at cut-off ≥14.43 pg/ml at sensitivity 71.2% and specificity 62% (OR = 4.04; 95%CI = 2.77-5.87). Woman with periodontal disease who later developed pre-eclampsia had lower levels of TNF-α (3.72 ± 1.33 pg/ml) than those with periodontal disease who did not develop pre-eclampsia (4.20 ± 2.15 pg/ml, p ≥ 0.05). CONCLUSION: Reduced TNF-α level secretion in the early second trimester in women with periodontal disease appears to be associated with the development of pre-eclampsia.

Correlation of the Day 3 FSH/LH Ratio and LH Concentration in Predicting IVF Outcome.

BACKGROUND: This study was undertaken to evaluate the role of day 3 FSH/LH ratio and day 3 LH level as predictors of IVF cycle outcomes. METHODS: This prospective observational study was undertaken in the IVF and Reproductive Biology Centre and Lok Nayak Hospital, affiliated to Maulana Azad Medical College, in New Delhi, India. The study included 105 women who underwent controlled ovarian hyperstimulation for in vitro fertilization. Characteristics of IVF cycles and outcomes were studied in patient subgroups based on day 3 FSH/LH ratio (<2 and ≥2) and day 3 LH levels (>3 and ≤3 mIU/ml). The student t-test, Bartlett's test, chi-squred (χ(2) ) and Fisher's exact test, and linear regression model were used for data analysis. A p-value less than 0.05 was considered as statistically significant. RESULTS: Women with an elevated FSH/LH ratio ≥2 (n = 31) required higher doses of gonadotrophins (3019.34 vs. 2482.43 IU). The outcome of IVF was poor in these patients and they had fewer number of mature follicles (>16 mm) (5.44 vs. 6.09), less E2/mature follicle ratio (4.65 vs. 6.36), fewer retrieved oocytes (6.67 vs. 9.09) and fewer pregnancy rates (11.1% vs. 33.8%). On the other hand, patients with low basal LH levels (≤3 mIU/ml) did not differ significantly in terms of response to controlled ovarian hyperstimulation except for fewer number of retrieved oocytes (7.33 vs. 7.91) but there was a trend towards poor pregnancy rates (7.33 vs. 7.91) but there was a trend towards poor pregnancy rates as compared to subgroup with LH levels >3 mIU/ml. CONCLUSION: Elevated day 3 FSH/LH ratio is associated with inferior outcome in IVF treatment cycles and it could be used as an additional predictor of decreased ovarian reserve.

IL-10, TNF-α & IFN-γ: potential early biomarkers for preeclampsia.

The present study was designed to evaluate levels of IL4, IL10, TNF-α & IFN-γ at early second trimester and 24h from delivery to assess potential correlation of cytokine variation with preeclampsia. A total of 176 consecutive healthy, normotensive primigravidas with uncomplicated singleton pregnancies were recruited at 14-18weeks of gestation. Serum cytokine levels were estimated at recruitment and 24h from delivery. In present study, 14(7.95%) women developed preeclampsia. Levels of IL-10, TNF-α and IFN-γ (Mean±SE) at recruitment were statistically significantly lower in preeclamptic group (39.21±9.46pg/mL, 73.57±13.37pg/mL and 0.70±0.20pg/mL, respectively) than non-preeclamptic group (86.02±4.55pg/mL, 601.37±63.54pg/mL and 1.67±0.08pg/mL, respectively) (p<0.05). In preeclamptic group, IL-4 and TNF-α levels (Mean±SE) were significantly higher 24h from delivery (5.35±0.95pg/mL and 381.21±43.28pg/mL, respectively) than at recruitment (2.39±0.71pg/mL and 73.57±13.37pg/mL) (p=0.019 and 0.0001, respectively) while IL-10 and IFN-γ levels decreased after delivery but the change was not statistically significant. Therefore, the levels of IL-10, TNF-α and IFN-γ between 14 and 18weeks of gestation may act as potential early biomarkers in the diagnosis of preeclampsia.

High prevalence of subclinical hypothyroidism during first trimester of pregnancy in North India.

BACKGROUND: Thyroid dysfunction is a common occurrence in pregnancy and affects both maternal and fetal outcomes. There are limited data on prevalence of hypothyroidism during pregnancy from India. Therefore, this study was designed to evaluate the prevalence of thyroid dysfunction especially hypothyroidism during first trimester in a large public hospital in North India. MATERIALS AND METHODS: All the consecutive first trimester pregnant women attending Lok Nayak and Kasturba Hospitals were enrolled in the study after institutional ethics approval and consent from the study subjects. The pregnant women with diagnosed thyroid disease and on thyroid medications were excluded from the study. Morning samples of study participants were analyzed for thyroid hormone profile which included free T3, free T4, TSH, and TPO Ab. In addition, all study participants were tested for CBC, LFT, KFT, and lipid profile. RESULTS: A total of 1000 women were enrolled for this prospective observational study. The mean (SD) age of study subjects was 25.6 (11.1) years, and mean (SD) gestational age was 10.3 (3.4) weeks. One hundred and forty-three (14.3%) subjects had TSH values more than 4.5 mIU/L above the cutoff used for definition of hypothyroidism. Out of these, 135 had normal free T4 and therefore labeled as subclinical hypothyroidism and 7 had low free T4 suggestive of overt hypothyroidism. TPO Ab was positive in 68 (6.82%) of total, 25 (18.5%) of subclinical and 5 (71%) of overt hypothyroid patients. CONCLUSION: Hypothyroidism, especially subclinical, is common in North Indian women during first trimester. Further countrywide studies are needed to evaluate the prevalence and etiology of hypothyroidism to prevent maternal and fetal adverse effects of hypothyroidism in India.

Is letrozole superior to clomiphene for ovarian stimulation prior to intrauterine insemination?

OBJECTIVE: To compare the efficacy of letrozole with clomiphene citrate for ovarian stimulation prior to intrauterine insemination. METHODS: A total of 272 patients underwent 362 cycles of stimulation prior to IUI from January 2009 to May 2011. One hundred and twenty-six patients (170 cycles) received letrozole 5 mg and 146 patients (192 cycles) received clomiphene citrate 100 mg for 5 days starting on day 3 of the cycle. Intrauterine insemination was done 36 ± 4 h after hCG injection in 99 patients (131 cycles) in the letrozole group and 115 patients (136 cycles) in the clomiphene group. The number of mature follicles and serum E2 levels was monitored on the day of hCG. Endometrial thickness was noted on the day of hCG and IUI as well. The pregnancy rate, the miscarriage rate, and other parameters were evaluated only for patients who underwent IUI. RESULTS: The mean number of mature follicles was significantly more in the clomiphene group (1.66 ± 1.69 vs. 1.41 ± 1.53) than in the letrozole group. No significant difference in endometrial thickness on the day of hCG administration was found; however, endometrial thickness was statistically significantly higher in the clomiphene group on the day of IUI (9.28 ± 1.43 vs. 8.77 ± 1.34). Serum E(2) levels on the day of hCG were statistically significantly higher in the clomiphene group (501.09 ± 2.45 vs. 214.79 ± 2.43 pg/ml). Pregnancy rate was 9.2 %/cycle and 12.12 %/patient in the letrozole group, and 8.1 %/cycle and 9.5 %/cycle in the clomiphene group; these differences were not statistically significant. CONCLUSION: This study found no superiority of letrozole over clomiphene when used for ovarian stimulation and IUI.