Acceptance of Elective Single-embryo Transfer in a Resource-limited Setting: A Cross-sectional Questionnaire-based Study.

Background: While elective single-embryo transfer (eSET) has been advocated in select countries, the global acceptance of the eSET policy has been undermined due to various issues. It is imperative to understand the couples' perspectives regarding the number of embryos transferred. Aims: We planned a study to evaluate the knowledge and attitude of infertile couples undergoing assisted reproductive technology towards eSET in self-funded treatment cycles in a low-resource setting. Settings and Design: We conducted a cross-sectional study at a tertiary-level referral facility between February 2020 and September 2022. Materials and Methods: This was an interviewer-administered questionnaire-based survey in two stages. The first stage involved the assessment of the knowledge of the participants. Following this, participants were given an information pamphlet and the second stage of the interview was conducted to assess the attitude and change in preference for embryo transfer number. Statistical Analysis Used: The Chi-square and Fisher's exact test were applied to find an association between categorical variables. Logistic regression was used to assess the association between factors and outcomes. Results: eSET was the preferred choice for only 5.8% of the participants. Following our educational intervention using an information leaflet, there was a statistically significant increase in the preference for eSET (P = 0.01). Univariate logistic regression analysis revealed that participants with a monthly income of ≤50,000 INR had a significantly higher preference for eSET. Conclusion: Continued emphasis on the risks of double-embryo transfer coupled with individualised selection criteria for eSET may help to achieve reasonable congruency between the clinician and couples' decision.

Comparison of Treatment outcomes following Ovarian Stimulation with Intrauterine Insemination in Minimal or Mild Endometriosis versus Unexplained Infertility: A Retrospective Cohort Study.

Background: Infertility is a global health issue. The variation in the prevalence of unexplained infertility is attributed to the choice of investigation. There remains a knowledge gap on the impact of minimal and mild endometriosis on treatment outcomes following intrauterine insemination (IUI). Aim: The aim of this study was to compare treatment outcomes following ovarian stimulation (OS) and intrauterine insemination (IUI) between minimal and mild endometriosis versus unexplained infertility. Settings and Design: A retrospective analysis of women undergoing OS with intrauterine insemination during the year 20142020 in the Department of Reproductive Medicine and Surgery, Christian Medical College, Vellore, was considered for the study. Materials and Methods: Women with minimal and mild endometriosis or unexplained infertility diagnosed by diagnostic hysterolaparoscopy were included for the analysis. Univariate and multivariate analysis was done. The primary outcome was live birth rate (LBR) per cycle. The secondary outcomes measured were clinical pregnancy rate (CPR) , cumulative LBR (CLBR) per women, cumulative CPR (CCPR) per women and miscarriage rate. Statistical Analysis Used: The baseline parameters were compared using a t-test for continuous data, and categorical data were compared using the Chi-square/Fisher's exact test as appropriate. The outcomes were assessed using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CI). Results: There were no significant differences in CPR per cycle (14.28% vs. 18.8%, OR: 0.71; 95% CI: 0.401.28) and LBR per cycle (14.28% vs. 16.6%, OR: 0.84; 95% CI: 0.461.51) between the endometriosis and unexplained infertility groups. The cumulative LBR per woman and CCPR per woman also did not show any significant difference in between the two groups. Conclusion: The current study did not find any significant differences in cumulative LBR and CPR following OS-IUI in women with minimal or mild endometriosis and unexplained infertility.

Seasonal Influence on Assisted Reproductive Technology Outcomes: A Retrospective Analysis of 1409 Cycles.

BACKGROUND: It is well known that seasonal variations influence natural conception and birth rates variably in different populations. It has been hypothesised that similar seasonal influences may affect treatment outcomes following assisted reproductive technology (ART). However, most studies report conflicting results. AIM: The aim of the study is to elucidate whether seasonality had any impact on the treatment success of the ART program. STUDY SETTING AND DESIGN: We conducted a retrospective cohort study at a university-level tertiary care hospital in South India. MATERIALS AND METHODS: All couples who underwent ART between January 2012 and December 2016 were included in the study. We divided the study population into three groups based on the seasonal differences experienced in our region. The primary outcome was live birth rate (LBR). STATISTICAL ANALYSIS: Univariate and multiple logistic regression models were used to compare outcomes and results reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: Univariate analysis revealed no significant difference in LBR in monsoon season (174/651, 26.7% vs. 83/319, 26.0%; OR 1.04, 95% CI 0.77,1.41; P = 0.81) as compared to summer. However, LBR was significantly higher in winter season (114/341, 33.4% vs. 83/319, 26.0%; OR 1.43; 95% CI: 1.02, 2.00; P = 0.04). Further, multivariate analysis following adjustment for various confounding factors revealed no significant statistical difference in LBR in monsoon (adjusted odds ratio [aOR], 0.92; 95% CI: 0.66, 1.26; P = 0.59) or winter (aOR 1.32; 95% CI: 0.92, 1.88; P = 0.13) as compared to summer season. CONCLUSION: The current study found no significant effect of seasonal variation on LBR following ART.

Letrozole as first-line drug for ovulation induction in treatment-naïve infertile polycystic ovarian syndrome women.

OBJECTIVE: One in seven couples is infertile and ovulatory dysfunction accounts for 25% of the cases. Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy associated with ovulatory dysfunction. Traditionally, clomiphene is considered the first-line drug for infertile PCOS women. Recently, letrozole was found to be an effective alternative ovulogen. The recent Cochrane review concluded that although live birth was higher with letrozole in unselected PCOS population, evidence was insufficient regarding effect of letrozole in treatment-naïve women. MATERIALS AND METHODS: We conducted a cohort study that included treatment-naïve infertile PCOS women at a tertiary level infertility center in South India. Participants in the prospective arm were given letrozole 2.5 mg daily for 5 days and the retrospective arm included women who had undergone ovulation induction with clomiphene (100 mg) for up to five treatment cycles. The primary outcome was ovulation rate. Secondary outcomes were clinical pregnancy, live birth, multiple pregnancy, and miscarriage rate. The trial was registered under the Clinical Trials Registry, India (CTRI/2018/07/014704). RESULTS: A total of 135 women in the letrozole group and 127 women in the clomiphene group underwent treatment. The ovulation rate per woman was similar in both groups (84.4% vs. 77.2%; p = 0.13). Letrozole was associated with significantly higher clinical pregnancy (38.5% vs. 22.0%; p = 0.004) and live birth rate per woman (30.3% vs. 18.9%; p = 0.03). CONCLUSION: The current study found letrozole to be a superior ovulation induction agent as compared to clomiphene in treatment-naïve infertile women with PCOS.

Perinatal Outcomes Using Ejaculate versus Surgical Sperm Retrieval in Patients Undergoing Intracytoplasmic Sperm Injection for Male Infertility - A Retrospective Analysis of 628 Cycles.

BACKGROUND: Men with azoospermia undergoing a surgical sperm retrieval are anxious about the well-being of the baby. It is therefore important to study the perinatal outcomes in this group compared to the ejaculate sample group. AIM: The aim of the study was to compare the perinatal outcomes between ejaculate and surgical sperm retrieval (SSR) groups in couples undergoing intracytoplasmic sperm injection for male factor. STUDY SETTING AND DESIGN: This was a retrospective cohort study conducted in a university-level infertility unit. MATERIALS AND METHODS: It is a retrospective cohort study analysis of 628 assisted reproductive technique (ART) cycles with male factor and combined (male and female) factor infertility over a period of 5 years (January 2011-December 2015). All women who underwent a fresh embryo ART cycle were followed up. The study population included the ejaculate and SSR groups. The perinatal outcomes of these two groups were compared. The congenital anomaly risks among the two groups were also analyzed. STATISTICAL ANALYSIS: Chi-square test, Fisher's exact test and Logistic regression. RESULTS: A total of 628 ART cycles were included in the current study, of which 478 cycles used ejaculate sperm, while SSR was done in 150 cycles. The analysis was restricted to singletons, and the risk of preterm birth was 22.9% in the ejaculate group, 5.9% in the epididymal group, and 12% in the testicular group (epididymal vs. ejaculate odds ratio [OR], 0.21; 95% confidence interval [CI]: 0.02-1.66) (testicular vs. ejaculate OR, 0.46; 95% CI: 0.12-1.65). The risk of low birth weight was 23.7% in the ejaculate group, 11.8% in the epididymal group, and 20.0% in the testicular group (epididymal vs. ejaculate OR, 0.42; 95% CI: 0.09-1.9) (testicular vs. ejaculate OR, 0.80; 95% CI: 0.27-2.3). The incidence of congenital anomalies was 7.3% in the ejaculate group, 0 in the epididymal group, and 3.5% in the testicular group (epididymal vs. ejaculate OR, 0.28; 95% CI: 0.01-5.2) (testicular vs. ejaculate OR, 0.63; 95% CI: 0.10-3.7) which was not significantly different. CONCLUSION: The current study showed no significant differences in the risk of adverse perinatal outcomes in the ejaculate group versus the surgically retrieved sperm groups.

Management of anxiety and pain perception in women undergoing office hysteroscopy: a systematic review.

PURPOSE: The aim of this review is to provide an overview of the literature about the perception and management of anxiety and pain in women undergoing an office hysteroscopic procedure. METHODS: We performed a systematic literature search in Embase, PubMed/MEDLINE, Cochrane Library and Web of Science for original studies written in English (registered in PROSPERO 2019-CRD42019132341), using the terms 'hysteroscopy' AND 'pain' AND 'anxiety' published up to January 2019. Only original articles (randomized, observational and retrospective studies) about management of anxiety and pain related to the hysteroscopic procedure were considered eligible. RESULTS: Our literature search produced 84 records. After exclusions, 11 studies including 2222 patients showed the following results: (a) pain experienced during hysteroscopy is negatively affected by preprocedural anxiety; (b) pharmacological interventions seem to be help in reducing pain during hysteroscopy; (c) waiting time before the procedure is a significant factor affecting patients' anxiety; (d) music during the procedure may be helpful in reducing anxiety. CONCLUSIONS: The utilization of office hysteroscopy is hampered by varying levels of anxiety and pain perceived by women who are candidates for the procedure. For these reasons, it is essential to identify effective pharmacological and non-pharmacological strategies to alleviate these factors. We recommend further studies especially focusing on non-pharmacological interventions to facilitate the dissemination of good clinical practices among hysteroscopists.

Management Strategies for POSEIDON Group 2.

Although individualization of ovarian stimulation aims at maximal efficacy and safety in assisted reproductive treatments, in its current form it is far from ideal in achieving the desired success in women with a low prognosis. This could be due a failure to identify such women who are likely to have a low prognosis with currently used prognostic characteristics. Introduction of the patient-oriented strategies encompassing individualized oocyte number (POSEIDON) concept reinforces recognizing such low prognosis groups and stratifying in accordance with important prognostic factors. The POSEIDON concept provides a practical approach to the management of these women and is a useful tool for both counseling and clinical management. In this commentary, we focus on likely management strategies for POSEIDON group 2 criteria.

Perinatal outcomes following IVF with use of donor versus partner sperm.

It is a matter of interest whether pregnancies with the use of donor sperm are associated with a higher risk of adverse perinatal outcomes compared with partner sperm. Anonymized data were obtained from the Human Fertilization & Embryology Authority. Data from 1991 to 2011 involving a total of 95,787 singleton births (4523 with donor sperm and 91,264 with partner sperm) following fresh IVF/intracytoplasmic sperm injection (ICSI) were analysed to compare perinatal outcomes of preterm birth (PTB), low birthweight (LBW) and high birthweight (HBW). The risk of LBW was significantly lower (adjusted odds ratio [aOR] 0.88, 95% confidence interval [CI]: 0.79-0.99) following donor sperm versus partner sperm IVF/ICSI. There was no significant difference in the risk of PTB (aOR 0.93, 95% CI: 0.83-1.04), early PTB (aOR 0.86, 95% CI: 0.67-1.11), very LBW (aOR 0.95, 95% CI: 0.75-1.20), HBW (aOR 1.09, 95% CI: 0.98-1.21) and very HBW (aOR 1.15, 95% CI: 0.90-1.45) following donor sperm versus partner sperm IVF/ICSI. The current study did not demonstrate an increased risk of adverse perinatal outcomes following donor sperm compared with partner sperm IVF/ICSI treatment.

Use of embryo culture supernatant to improve clinical outcomes in assisted reproductive technology: a systematic review and meta-analysis.

We planned a systematic review and meta-analysis of randomized clinical trials (RCTs) to examine the best available evidence regarding the intrauterine instillation of embryo culture supernatant prior to embryo transfer in ART. The outcomes were: (i) live birth; (ii) clinical pregnancy; (iii) multiple pregnancy; and (iv) miscarriage rates. Five RCTs were considered eligible and available for qualitative synthesis. Due to clinical heterogeneity, results from only two trials were combined for the meta-analysis. The live birth rate (risk ratio [RR], 0.47; 95% confidence interval [CI] 0.22-0.98; one study, 60 participants, low-quality evidence) was found to be significantly lower with intrauterine instillation of embryo culture supernatant compared to no intervention. The clinical pregnancy rate was similar between the embryo culture supernatant group and the control group (RR 1.02 RR, 95% CI 0.77-1.36; two trials, 156 participants, I2 = 0%). To conclude, this review did not find any improvement in clinical pregnancy rate with the intrauterine instillation of embryo culture supernatant prior to embryo transfer compared to no intervention in women undergoing ART and we remain uncertain regarding its effect on live birth rate.

Perinatal outcomes after stimulated versus natural cycle IVF: a systematic review and meta-analysis.

Pregnancies resulting from assisted reproductive techniques are at higher risk of adverse perinatal outcomes compared with spontaneous conceptions. Underlying infertility and IVF procedures have been linked to adverse perinatal outcomes. It is important to know if ovarian stimulation influences perinatal outcomes after IVF. A systematic search for relevant studies was conducted up to November 2016 on the following databases: PubMed, EMBASE, DARE and Cochrane Central Register of Controlled Trials. Perinatal outcomes included preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), large for gestational age (LGA) and congenital anomalies. Data from four studies, which included a total of 96,996 and 704 singleton live births after stimulated IVF and natural or modified natural cycle IVF, were included in the meta-analysis. The risk of PTB (RR 1.27, 95% CI 1.03 to 1.58) and LBW (RR 1.95, 95% CI 1.03 to 3.67) were significantly higher after stimulated compared with natural or modified natural cycle IVF. Data from one study were available for SGA, LGA, congenital anomalies and no significant differences were reported between the groups. This study suggests a higher risk of PTB and LBW after stimulated IVF compared with natural or modified natural IVF, although the absolute increase in risk may be low.

High-risk of preterm birth and low birth weight after oocyte donation IVF: analysis of 133,785 live births.

A higher risk of pregnancy complications occurs after assisted reproductive techniques compared with spontaneously conceived pregnancies. This is attributed to the underlying infertility and assisted reproduction technique procedures involved during treatment. It is a matter of interest whether use of donor oocytes affects perinatal outcomes compared with pregnancies after autologous IVF. Anonymized data were obtained from the Human Fertilization and Embryology Authority. The analysis included 5929 oocyte donation and 127,856 autologous IVF live births. Data from all women who underwent donor oocyte recipient or autologous IVF cycles, both followed with fresh embryo transfer, were analysed to compare perinatal outcomes of preterm birth (PTB) and low birthweight (LBW) after singleton and multiple live births. The risk of adverse perinatal outcomes after oocyte donation was increased: adjusted OR (aOR) 1.56, 99.5% CI 1.34 to 1.80 for PTB and aOR 1.43, 99.5% CI 1.24 to 1.66 for LBW were significantly higher after oocyte donation compared with autologous IVF singletons. The adjusted odds PTB (aOR 1.21, 99.5% CI 1.02 to 1.43) was significantly higher after oocyte donation compared with autologous IVF multiple births. Analysis of this large dataset suggests significantly higher risk of PTB and LBW after ooctye donation compared with autologous IVF pregnancies.

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.

Affordable ART: a different perspective.

BACKGROUND: Although ≈ 10% of the population is affected by infertility, the treatment option of in-vitro fertilisation (IVF) remains unaffordable for the majority of infertile couples. We have initiated a lowcost programme incorporating an uncommonly used, but recognized, ovarian stimulation protocol, together with certain costlimiting initiatives in an established assisted reproductive technology (ART) set up. METHODS: The medical records of women who underwent the lowcost programme were analysed. Clomiphene citrate 50 mg daily was administered from Day 2 of the cycle and continued till the day of hCG trigger, thus preventing the LH surge. Intermittent doses of human menopausal gonadotrophin 150 IU were administered on alternate days from the 5th day onwards. Oocyte retrieval was carried out once at least two follicles of >18 mm were identified. The cycle was monitored by ultrasound only, with embryo transfer being carried out on Day 3. Clinical outcomes were recorded together with an estimation of the direct costs per cycle. Direct cost calculations did not include professional charges or facility costs. RESULTS: Of 143 women evaluated, 104 women underwent embryo transfer. The live birth rate and clinical pregnancy rate per embryo transfer were 19 and 22%. The live birth rate per initiated cycle was 14% (20/143). The multiple pregnancy rate was 26% with no case of ovarian hyperstimulation syndrome being recorded. The average direct cost per cycle was US$ 675 for IVF and US$ 725 for an ICSI treatment cycle. CONCLUSIONS: Using this protocol, together with several costcutting measures, we achieved an acceptable live birth rate per transfer of 19% at a reasonable cost. This approach could be used by established ART centres to provide treatment to couples who cannot afford conventional ART.