Dietary pattern characterisation among subfertile South Asian women and the impact of vitamin B12 intake on frozen embryo transfer outcomes: a cross-sectional study.

STUDY QUESTION: Is there a difference in dietary patterns among subfertile South Asian women undergoing frozen embryo transfer (FET)? SUMMARY ANSWER: Significant regional differences in dietary pattern exist among subfertile South Asian women undergoing FET. WHAT IS KNOWN ALREADY: Preconception consumption of certain food groups or adopting specific dietary patterns, such as the 'Mediterranean diet', and its level of adherence have been shown to enhance the odds of achieving a successful pregnancy in women undergoing ART. However, differences in geographic location, individual preference, cultural beliefs and local availability contribute to such dietary choices. There is also a predisposition to a vitamin B12 deficiency in those of South Asian ethnicity and a predominant pattern of vegetarian food intake. There is a paucity of studies analysing the type of dietary pattern followed by South Asian women, their vitamin B12 levels and the potential impact on ART treatment outcomes. STUDY DESIGN SIZE DURATION: This is a cross-sectional study of 159 South Asian women aged 21-37 years, belonging to the Eastern (n = 75) and Southern (n = 84) regions of India plus Bangladesh, and undergoing a FET cycle at a tertiary level infertility clinic between February 2019 and March 2020. PARTICIPANTS/MATERIALS SETTING METHODS: Women underwent dietary assessment using '24-hour dietary recall' to capture daily nutrient consumption. A 'Food Frequency Questionnaire' listing commonly consumed foods was used to record frequency of intake. The primary outcome was the characterisation of regional dietary patterns in the cohorts using principal component analysis (PCA). Secondary outcomes included association of vitamin B12 intake and serum levels with clinical and ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Four components contributing to overall variance in dietary pattern were identified, namely: meat, poultry and seafood; green leafy vegetables and root tubers; fruits, dairy and sugar; nuts and oilseeds. PCA analysis showed a significantly higher consumption of two components in the East-meat, poultry and fish (P < 0.001); green leafy vegetables and root tubers (P < 0.001). All women reported taking preconception oral folic acid supplementation. The dietary intake of vitamin B12 and serum concentration correlated, showing a good validity of measured dietary intake (r = 0.398; P ≤ 0.001). Compared to the Southern region, participants from the East showed a higher daily median intake of vitamin B12 (1.11 versus 0.28 mcg, respectively; P < 0.001) and a higher serum vitamin B12 levels (441 versus 239 pg/ml, respectively; P < 0.001). Ongoing pregnancy showed no association with dietary vitamin B12 intake (relative risk 0.90; 95% CI, 0.68 to 1.19) or serum vitamin B12 levels (relative risk 0.99; 95% CI, 0.73 to 1.33) after adjustments for female age, body mass index (BMI) and geographic differences. Women belonging to different quartiles of serum vitamin B12 concentration had a similar likelihood of ongoing pregnancy. LIMITATIONS REASONS FOR CAUTION: Self-reported dietary assessment is prone to measurement errors owing to its subjective nature and recall bias. The study was not adequately powered to detect the impact of geographic differences in vitamin B12 intake and serum levels on FET treatment outcomes, the second objective. We adjusted for potential confounders, such as female age and BMI, but it is possible that residual confounders, such as physical activity, stress and use of dietary supplements, may have influenced the results. Extrapolation of the study findings to women undergoing ART in other populations should be made with caution. WIDER IMPLICATIONS OF THE FINDINGS: Our study findings suggest important differences in local dietary patterns within the South Asian region. Hence a personalised approach to dietary assessment and intervention when undergoing ART based on population dynamics is warranted. The geographic differences in the vitamin B12 intake or serum levels did not have an impact on the FET outcomes. There is also a need to further investigate the impact of such dietary differences on ART treatment outcomes in a large study population. STUDY FUNDING/COMPETING INTERESTS: No grant from funding agencies in the public, commercial, or not-for-profit sectors was obtained. The authors have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

Comparison of Perinatal Outcomes of Singletons Following Vanishing Twin Phenomenon and Singletons with Initial Single Gestational Sac Conceived Following Assisted Reproductive Technology: A Retrospective Analysis.

AIM: The aim of the study was to compare the perinatal outcomes between singletons following vanishing twin phenomenon and singletons arising from initial single gestational sac following assisted reproductive technology (ART) treatment. SETTING AND DESIGN: This was a retrospective cohort study. MATERIALS AND METHODS: A retrospective cohort study included analysis of all singleton births following ART over a period of 7 years (January 2010 -December 2016). All women who underwent fresh or frozen embryo ART cycles were followed up. The study population included all singleton births following spontaneous reduction of one of the gestational sacs in dichorionic diamniotic twin pregnancies. The perinatal outcome of this group was compared with those of singletons arising from the initial single gestational sac. RESULTS: A total of 521 singleton births were recorded during the study period. In the study group, 72 singleton births had spontaneous reduction of one of the gestational sacs (vanishing twin group) and the remaining 449 had an initial single gestational sac. The risk for low birth weight (LBW) (14/72, 19.4% vs. 96/449, 21.6%) and preterm birth (PTB) (17/72, 23.6% vs. 134/449, 29.8%) was not significantly different between those singletons who had spontaneous reduction from two gestational sacs to single sac compared to those with initial single sac. The miscarriage rate was significantly lower in vanishing twin group compared to control group (7/84, 8.3% vs. 157/622, 25.2%; P = 0.01). The subgroup analysis based on spontaneous reduction occurring before or after the appearance of the embryonic pole also showed similar risk of PTB (11/41, 26.8.% vs. 9/31, 29.0%) and LBW (7/41, 17.1% vs. 9/31, 29.0%). CONCLUSION: Perinatal outcomes in singleton live births following vanishing twin phenomenon are similar to those pregnancies with an initial single gestational sac following ART.

Knowledge and attitudes of subfertile couples towards disposition of supernumerary cryopreserved embryos: an Indian perspective.

In many cases, supernumerary embryos are cryopreserved for future use following assisted reproductive technology (ART) treatment. Once a couple has completed their family following treatment, the fate of these excess cryopreserved embryos becomes uncertain. The options available for the disposition of cryopreserved embryos are donation to other infertile couples, donation to research and discontinuation of cryostorage. In order to evaluate the knowledge and attitudes of subfertile couples from the Indian subcontinent regarding the fate of their excess cryopreserved embryos, a cross-sectional study was planned at a university-level infertility unit. A two-stage structured interview was conducted with the couples. Some questions in the interview were hypothetical in nature. In total, 87 couples were interviewed, of which 33 (37.9%) were unaware of the options for disposition of supernumerary embryos. Forty (46%) couples indicated a preference to donate their embryos to other subfertile couples, while 10 (11.5%) couples preferred donation to research. Twenty-four (27.6%) couples opted for donation to both other couples and research, while three (3.4%) couples indicated a preference to discontinue storage. Penalized bivariable logistic regression showed that none of the factors examined (i.e. age, education, income or presence of a living child) influenced the couple's decision regarding embryo donation. The majority of subfertile couples preferred to donate the embryos rather than discontinue storage. The donation of embryos to other subfertile couples was the most preferred option for disposition of embryos.

Prevalence of vitamin D deficiency in infertile women with polycystic ovarian syndrome and its association with metabolic syndrome - A prospective observational study.

OBJECTIVE: The main purpose of this study was to determine the prevalence of vitamin D deficiency in infertile women with polycystic ovarian syndrome (PCOS) and to explore the association of hypovitaminosis D with metabolic syndrome in women with PCOS. STUDY DESIGN: A prospective observational study was conducted in a tertiary care, infertility centre from March 2016 to March 2017. The primary outcome was estimation of the prevalence of vitamin D deficiency in infertile PCOS women. Secondary outcomes were to study the association of hypovitaminosis D with metabolic syndrome, obesity and hypercholesterolemia in PCOS patients. RESULTS: A total of 256 infertile women with PCOS were included in the study. Vitamin D deficiency was observed in 70.3% women, 20.3% were vitamin D insufficient and only 9.4% were vitamin D sufficient. Metabolic syndrome was seen in 80/256 (31.25%) women. There was no evidence of an association between hypovitaminosis D and metabolic syndrome, obesity or hyperlipidemia. There was a strong evidence of an association between waist circumference of >80 cm and vitamin D deficiency (p = 0.02). CONCLUSION: Vitamin D deficiency is highly prevalent in infertile PCOS women and there seems to be no association between hypovitaminosis D and the metabolic syndrome in the same population.

Effectiveness of Anti-Mullerian Hormone-tailored Protocol Compared to Conventional Protocol in Women Undergoing In vitro Fertilization: A Randomized Controlled Trial.

BACKGROUND: Assessment of ovarian reserve before an in vitro fertilization cycle (IVF) is one among the many factors that predicts a successful cycle. Individualized protocol based on ovarian reserve is designed to optimize the pregnancy outcome without compromising the patient safety. Although authors have shown that anti-Mullerian hormone-tailored (AMH) protocols have reduced the treatment burden and improved pregnancy rates, a few others have questioned its efficacy. AIMS: The aim of this study was to decide whether the AMH-tailored protocol or the conventional protocol better decides IVF outcomes. SETTING AND DESIGN: Prospective randomized controlled trial conducted at a tertiary level university hospital. MATERIALS AND METHODS: Patients undergoing theirfirst IVF cycle who fulfilled the inclusion criteria were recruited and randomized to each group. Serum follicle-stimulating hormone was done for the patients on day 2 or 3 of a prior menstrual cycle, and serum AMH was done in the preceding cycle. STATISTICAL ANALYSIS: Analysis was performed using SPSS software version 16. RESULTS AND CONCLUSION: There were 100 patients in each group. A total of 83 patients underwent embryo transfer in the conventional group and 78 patients in the AMH group. The clinical pregnancy rates per initiated cycle (36.4% vs. 33.3%) and per embryo transfer (45.1% vs. 41.3%) were similar in both the groups. There was no statistical difference in the number of cycles cancelled due to poor response or the risk of ovarian hyperstimulation syndrome in both the groups. Hence, this study showed the similar effectiveness of AMH-tailored protocol and conventional protocol in women undergoing IVF.

Patient Experience with Conscious Sedation as a Method of Pain Relief for Transvaginal Oocyte Retrieval: A Cross Sectional Study.

AIM: The aim of the study was to measure patient's satisfaction level and acceptance of conscious sedation as a method of pain relief following transvaginal oocyte retrieval (TVOR) during assisted reproduction technology treatment. We also evaluated the factors that may influence the efficacy of conscious sedation method. SETTING AND DESIGN: A prospective cross-sectional study. MATERIALS AND METHODS: Prospective study was conducted from October 2015 to January 2016 at a university-level hospital and 100 women were recruited. Variables for analysis included woman age, duration of procedure, number of oocytes retrieved, and transmyometrial passage of the needle. Pain assessment was done by visual analog scale (VAS). Medical complications, and patient satisfaction score [Likert's score and client satisfaction questionnaire (CSQ)] were recorded. RESULTS: There was a moderate positive correlation between age and pain score on day 1 post-procedure. When the duration of procedure was >12 min, immediate post-procedure pain score was significantly higher compared to those whose procedure where duration was <12 min. There was no correlation between pain score and the number of oocytes retrieved (≤5, 6-15, and ≥16) and transmyometrial passage of needle. The VAS 10-point score immediately post-procedure, after 6 and 24 h post-procedure, and on day of embryo transfer was 2.83 (±1.67), 0.78 (±1.04), 0.39 (±1.09), and 0.14 (±0.58), respectively. The Likert's score was 3.65 (±0.82) and mean CSQ was 27.04 (±3.01). Majority of the women (86%) preferred the same pain relief method for future analgesia. There were no major complications. CONCLUSION: Conscious sedation was associated with high satisfaction level and acceptance rate among patients undergoing TVOR.

Progesterone/Estradiol Ratio as a Predictor in the ART Cycles with Premature Progesterone Elevation on the Day of hCG Trigger.

BACKGROUND: The purpose of the study was to evaluate the role of Progesterone/ Estradiol (P4/E2) ratio as a predictive tool for clinical pregnancy in ART cycles with a premature progesterone rise of >1.5 ng/ml on the day of human chorionic gonadotropin (hCG) trigger. METHODS: Retrospective analysis was done on 569 fresh embryo transfer cycles from January 2011 to December 2012 at the infertility unit of a tertiary care hospital. Age, BMI, number of cycles and number of clinical pregnancies have been considered. RESULTS: The overall clinical pregnancy rate per embryo transfer was 42.8% (244/569). The clinical pregnancy rate in the 36 cycles with progesterone (P4) level >1.5 ng/ml was significantly lower than the 533 cycles with normal p4 ≤1.5 ng/ml (22.2% vs. 44.2%; p=0.0092). The 36 cycles with progesterone level >1.5 ng/ml were divided into subgroups of P4/E2 >1 (n=20) and P4/E2 ≤1 (n=16). The 20 cycles with P4/E2 >1 and P4 >1.5 ng/ml had a significantly lower pregnancy rate than the cycles with P4 ≤1.5 ng/ml (15% vs. 42.8%; p=0.0103). The 15 cycles with P4/E2 ≤1 and P4 >1.5 ng/ml had a similar pregnancy rate as the cycles with P4 ≤1.5 ng/ml. CONCLUSION: A premature progesterone elevation in ART cycles is possibly associated with lower clinical pregnancy rates; this adverse impact of elevated progesterone seems to be limited mainly to a subgroup with an elevated P4/E2 ratio >1.

Obstetric outcomes of monochorionic pregnancies conceived following assisted reproductive technology: A retrospective study.

OBJECTIVES: The overwhelming numbers of twins following assisted reproductive technology (ART) are dichorionic twins, but monochorionic twins account for around 0.9% of post ART pregnancies. The data for post ART-monochorionic pregnancy outcomes are scarce due to the rarity of this condition. Hence, we evaluated the obstetric outcomes of monochorionic and dichorionic pregnancies conceived on ART. SETTINGS: University teaching hospital. STUDY DESIGN: A case-control study of monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) pregnancies conceived following ART treatment. Charts of all women who conceived following ART from 2008 to 2013 were screened. Among them, the monochorionic twins diagnosed in the first trimester were included and their obstetric outcome was followed-up. For comparison, an equal number of dichorionic twin pregnancies from age and body mass index matched mothers was selected. RESULTS: The baseline clinical characteristics were similar between the two groups. MCDA group had a higher miscarriage rate (50%) than the DCDA group (10%), with three seconds trimester miscarriages in the MCDA group. The live birth rates were lower in the MCDA versus DCDA group (40% vs. 90%). Among triplet pregnancies with a monochorionic component, the live birth rate was only 25%. CONCLUSIONS: Monochorionic pregnancies following ART have poorer obstetric outcomes when compared to dichorionic pregnancies. For monochorionic pregnancies following ART, intensive antenatal surveillance at a tertiary level obstetric and neonatal center may help optimize the outcome.

Comparison of clinical outcomes following vitrified warmed day 5/6 blastocyst transfers using solid surface methodology with fresh blastocyst transfers.

OBJECTIVES: The literature regarding clinical outcomes following day 5/6 vitrified warmed blastocysts transfer has been conflicting. We decided to evaluate and compare the clinical outcomes following vitrified warmed day 5/6 blastocyst transfer using a solid surface vitrification protocol with fresh blastocyst transfers. SETTINGS: University teaching hospital. STUDY DESIGN: A total of 249 women were retrospectively analyzed: 146 fresh day 5 blastocyst (group 1), 57 day 5 vitrified warmed blastocyst (group 2), and 46 vitrified warmed day 6 blastocyst (group 3) transfer cycles. Vitrification was done using solid surface methodology (non immersion protocol). The main outcomes were implantation rates, clinical pregnancy, and live birth rate per embryo transfer. RESULTS: The baseline clinical characteristics were similar among all three groups. The implantation and clinical pregnancy rates following vitrified warmed day 6 blastocyst transfers (20.9% and 32.6%) were significantly lower as compared to day 5 fresh and vitrified warmed day 5 blastocyst transfers (40.3% and 56.1%, 36.3%, and 52.6%). However, there was no significant difference in the live birth rates across the three groups (group 1: 37.6%, group 2: 40.3%, and group 3: 28.2%). CONCLUSION: No statistically significant difference was observed in live birth rates between fresh day 5 blastocyst transfers and vitrified warmed day 5/6 blastocyst transfers. Vitrification of blastocysts using solid surface methodology is an efficient method of cryopreservation.

Prevalence of metabolic syndrome in women with polycystic ovary syndrome attending an infertility clinic in a tertiary care hospital in south India.

OBJECTIVE: The aim of the present study was to evaluate the prevalence of metabolic syndrome in women with polycystic ovary syndrome (PCOS). SETTING: Infertility clinic in a tertiary care hospital. STUDY DESIGN: A prospective cross-sectional study. MATERIALS AND METHODS: All the women attending the infertility clinic categorized as polycystic ovary syndrome according to Rotterdam criteria (2003) during the study period were included in the study. The women with PCOS underwent screening for metabolic syndrome as defined by the modified American Heart Association/National Heart Lung Blood Institute (AHA/NHLBI) modified ATP 111 (2005) definition. A multivariate logistic regression analysis was applied and significant predictors identified for the prediction of metabolic syndrome. RESULTS: The overall prevalence of metabolic syndrome according to the modified AHA/NHLBI ATP III (2005) criteria was 37.5%. A total of 5.8 % cases were detected to have diabetes mellitus, 8.3% had impaired fasting glucose, and 11.7 % had an impaired glucose test. Dyslipidemia was present in 93.3% cases of PCOS. Among all the risk factors, age and waist hip ratio ≥0.85 were strongly associated with the presence of metabolic syndrome. CONCLUSION: Infertile women with PCOS, particularly those with age ≥25 years or with central obesity (a waist hip ratio of ≥0.85), are at a higher risk of developing metabolic syndrome and should be offered screening tests.

Aromatase inhibitors in women with clomiphene citrate resistance: a randomized, double-blind, placebo-controlled trial.

In 36 women with polycystic ovary syndrome and clomiphene citrate resistance, letrozole, an aromatase inhibitor, statistically significantly increased the ovulation rate by 33.3% in the treatment group, indicating that letrozole can be used as an effective and simple alternate ovulation-inducing agent in these women.

hCG administration offers no outcome benefit over spontaneous ovulation in anovulatory women treated with clomiphene citrate.

This randomized controlled trial compared spontaneous ovulation versus hCG-triggered ovulation in anovulatory women treated with clomiphene citrate. No statistically significant differences were observed between the two groups in terms of ovulation and pregnancy rates.

Factors predicting the outcome of intracytoplasmic sperm injection for infertility.

BACKGROUND: Male factor abnormality is the cause of infertility in about 20%-40% of infertile couples. Assisted reproduction with intracytoplasmic sperm injection is the only treatment option for severe forms of andrological infertility. METHODS: We retrospectively analysed patients who had had intracytoplasmic sperm injection for male factor infertility. The clinical and laboratory factors that influenced the pregnancy rate were also analysed. RESULTS: One hundred and seventy-five cycles in 164 couples were analysed. The fertilization, cleavage and pregnancy rates were similar in the groups that had had intracytoplasmic sperm injection with epididymal, testicular or ejaculate sperm. Univariate analysis of the clinical variables showed progressive reduction in pregnancy rate with increase in the woman partner's age and body mass index, and presence of pelvic disease, but these were not statistically significant. The age of the woman was the most significant factor affecting the pregnancy rate after adjusting for body mass index and pelvic disease in the multivariate analysis (OR 0.26, 95% CI: 0.08-0.84, p=0.03). The oocyte number, embryo transfer number and transfer day had no significant influence on the outcome. CONCLUSION: The woman partner's age influences the success of assisted reproduction with intracytoplasmic sperm injection in male factor infertility. Thus, the chances of success are better if the couple seeks treatment at an early age.