Impact of tubal patency test selection on the live birth rate following intrauterine insemination in couples with unexplained infertility: a retrospective cohort study.

OBJECTIVE: We planned a study to evaluate the impact of selecting hysterosalpingography (HSG) over diagnostic laparoscopy during initial fertility evaluation on IUI treatment outcomes in couples diagnosed with unexplained infertility. METHODS: The study comprised a retrospective cohort and included couples evaluated for infertility at our tertiary level hospital between January 2008 and December 2019. Couples diagnosed with unexplained infertility based on tubal patency tests (either HSG or diagnostic laparoscopy) were included. We compared outcomes following ovarian stimulation (OS) and intrauterine insemination (IUI) between women who underwent HSG versus laparoscopy for up to three treatment cycles. RESULTS: A total of 7413 women were screened, out of which 1002 women were diagnosed with unexplained infertility. We did not find a significant statistical difference in the clinical pregnancy (16.7% vs. 11.7%; OR (odds ratio) 1.51; 95% CI (confidence interval) 0.90-2.5) or live birth rate per IUI cycle (15.1% vs. 10.7%; OR 1.51, 95% CI 0.9-2.6) in women who underwent HSG for tubal evaluation as compared to laparoscopy. After adjustment for potential confounders through multivariate analysis, we found that outcomes were comparable between the HSG and laparoscopy. CONCLUSION: The current study did not find any significant difference in treatment outcomes following OS and IUI in women with unexplained infertility who underwent HSG compared to laparoscopy for the assessment of the tubal patency during the initial fertility workup. The finding suggests minimal or no impact of selecting HSG over diagnostic laparoscopy as a tubal patency test on the subsequent IUI outcomes.

Effectiveness of music therapy as an adjuvant to conscious sedation in women undergoing transvaginal oocyte retrieval: A randomized controlled trial.

AIM: Assisted reproductive technique (ART) has emerged as the highest form of treatment for infertile couples. Transvaginal oocyte retrieval is currently performed under conscious sedation in most centers. Since it is a relatively painful procedure, a number of adjuvant therapies have been tried to improve pain relief during the procedure. Music therapy is a nonpharmacological technique that has been successfully used for pain relief in perioperative and chronic pain of malignancy. However, studies evaluating its usefulness in ART-related procedures are limited. We evaluated the effectiveness of music therapy as an adjuvant for pain relief during oocyte retrieval. METHODS: This was a randomized controlled trial conducted at a tertiary level teaching hospital in South India from September 2020 to March 2021. All women undergoing transvaginal oocyte retrieval were randomized to receive either music therapy along with conscious sedation (Group A) or conscious sedation alone (Group B). The primary outcome was postprocedure pain score assessed by the visual analog scale. Secondary outcomes included anxiety score. RESULTS: A total of 109 women were randomized into Group A (54 women) and Group B (55 women). The postprocedure pain score was comparable between the two study groups (6.0, interquartile range [IQR] 4 to 6 vs. 6.0, IQR 4 to 6; p = 0.69). However, anxiety levels were found to be significantly lower in women who were offered music therapy (3.0, IQR 1 to 5 vs. 4.0, IQR 3 to 6; p = 0.004). CONCLUSION: The use of music therapy as an adjuvant to conscious sedation was found to have no significant benefit in pain relief during oocyte retrieval.

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.

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.

Comparing Obstetric and Perinatal Outcomes Following Elective and Emergency Cervical Cerclage in Singleton and Multiple Pregnancies in a Tertiary Care Perinatal Centre.

Objective: To compare the success, failure rates and perinatal outcomes following emergency and elective cervical cerclage in singleton and twin pregnancies at a tertiary care perinatal centre over half a decade. Methods: All pregnant women, both with singleton and twin pregnancies, who had cervical cerclage between June 2014 and May 2019 were included in the retrospective study. Success rates, failure rates, maternal complications and perinatal outcomes were compared in both groups. Results: There were 129 women enrolled in the study, 48 in the emergency and 81 in the elective group. A significantly greater number of multiparous women were in the elective group (97.5% versus 68.7%; p-value < 0.001). Twins were nearly four times more in the emergency group as compared to  the elective group. The mean cervical length at time of cerclage was 2.05 cm and 1.5 cm; (p-value < 0.001) respectively in the elective and emergency groups. Almost half of the women in the emergency group had bulging membranes. (52.2%). Following cerclage, mean gestational age at delivery was similar in both groups. However, more women in the elective group delivered at or beyond 34 weeks in comparison to the emergency groups (71% versus 53.3%. P-value 0.05). Preterm labour leading to preterm births was almost twice in the emergency group than elective group (49% versus 22%, P-value 0.002). Rates of maternal chorioamnionitis were similar in both groups. The overall live birth rates were comparable (81.3% versus 84.4% P-value 0.85) in both the groups. These results were also seen on doing subgroup analysis of elective versus emergency cerclage in singleton pregnancies only. Failure rates were also similar in both groups (18.7% versus 15.6%, P-value 0.85) Composite neonatal morbidity was more in the emergency group than in the elective group (35.5 versus 14%, P-value 0.01). Conclusion: Live birth rates and failure rates were comparable following elective and emergency cerclage both overall and in singleton pregnancies. Maternal chorioamnionitis and neonatal sepsis  rates were similar in both the groups. However, composite neonatal morbidity was higher in the emergency cerclage group.

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.

Knowledge, anxiety levels and attitudes of infertile couples towards COVID-19 and its impact on self-funded fertility treatment: a cross-sectional questionnaire survey.

STUDY QUESTION: What is the knowledge, anxiety levels and attitudes of infertile couples towards coronavirus disease 2019 (COVID-19) and its impact on undergoing self-funded treatment cycles? SUMMARY ANSWER: In spite of a high level of awareness about COVID-19, anxiety levels were low and many participants wanted to continue fertility treatment during the pandemic. WHAT IS KNOWN ALREADY: The COVID-19 pandemic has strained the already overburdened public health infrastructure in many of the resource-limited settings across the world. After an initial decision to suspend fertility treatments, regulatory authorities advocated phased resumptions of treatment. Owing to limited healthcare resources and the detrimental impact of COVID-19 on the economy and job losses, fertility services have been disproportionately affected. It is important to understand the perceptions of infertile couples, who are the key stakeholders in shared decision-making, especially for self-funded treatments, on the continuation of fertility treatment during the current COVID-19 pandemic. STUDY DESIGN SIZE DURATION: This was a questionnaire-based cross-sectional study conducted among 502 participants (251 infertile couples) at a tertiary level infertility clinic between May 2020 and November 2020. The study recruitment period (6 months) coincided with the increase and peak of COVID-19 infection in India. The study included infertile couples who had attended the clinic either for assessment or fertility treatment. PARTICIPANTS/MATERIALS SETTING METHODS: An interviewer administered the questionnaire survey, which was conducted in two stages for each participant. In the first stage, knowledge about COVID-19 and anxiety levels caused by the ongoing pandemic were assessed using a validated Generalized Anxiety Disorder-7 (GAD-7) tool. Following this, all the participants were provided with a COVID-19 information pamphlet. Subsequently, in the second stage, participants were administered another questionnaire to assess their attitudes towards fertility treatment and pregnancy during the COVID-19 pandemic. MAIN RESULTS AND THE ROLE OF CHANCE: The results showed that the knowledge levels and awareness about COVID-19 was high among infertile couples attending the infertility clinic. The majority of the participants were aware of the mode of spread (87.6-93.4% correct answers to different questions), common symptoms (64.1-96.2%) and the importance of preventative measures (95.6-97.4%). Most of the participants (474/502; 94.4%) did not show anxiety when being assessed using GAD-7. A vast majority (96.5-99.2%) of the participants were in agreement with the need for following preventative measures for reducing the spread of COVID-19. About one-third of the participants wanted to delay the fertility treatment until the pandemic is over (166/502; 33.1%). Approximately 42.2% (212/502) of the participants did not feel the need to suspend fertility treatment during the pandemic. Further analysis revealed that participants' education levels significantly influenced the desire to continue fertility treatment: participants with lower levels of education (below graduate) were less likely to continue fertility treatment (adjusted odds ratio 0.34, 95% CI, 0.12-0.98). LIMITATIONS REASONS FOR CAUTION: Questionnaire-based responses could have limited the ability of the interviewer to capture the entire range of thoughts and views of the participants on the COVID pandemic and their fertility treatments. Furthermore, a language barrier was encountered for some couples for which assistance from a translator was sought. WIDER IMPLICATIONS OF THE FINDINGS: Given the impact of infertility and the associated stigma, public health policy makers, regulatory authorities and fertility societies should consider a way to sustain the treatment options and develop appropriate guidelines to continue treatment, particularly when much of the world is experiencing the second and third waves of the COVID pandemic. STUDY FUNDING/COMPETING INTERESTS: This study has not received any specific grant from funding agencies in the public, commercial or not-for-profit sectors. M.S.K. is an associate editor with Human Reproduction Open. The other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Antioxidant pretreatment for male partner before ART for male factor subfertility: a randomized controlled trial.

STUDY QUESTION: Does oral antioxidant pretreatment for the male partner improve clinical pregnancy rate in couples undergoing ART for male factor subfertility? SUMMARY ANSWER: There was no significant difference in clinical pregnancy rate following oral antioxidant pretreatment for male partner in couples undergoing ART for male factor subfertility compared to no pretreatment. WHAT IS KNOWN ALREADY: Damage to sperm mediated by reactive oxygen species (ROS) contributes significantly to male factor infertility. The ROS-related injury reduces fertilization potential and adversely affects the sperm DNA integrity. Antioxidants act as free radical scavengers to protect spermatozoa against ROS induced damage. During ART, use of sperms which have been exposed to ROS-mediated damage may affect the treatment outcome. Pretreatment with antioxidants may reduce the ROS-mediated sperm DNA damage. Currently, antioxidants are commonly prescribed to men who require ART for male factor subfertility but there is ambiguity regarding their role. STUDY DESIGN SIZE DURATION: This was an open label, randomized controlled trial conducted at a tertiary level infertility clinic between February 2013 and October 2019. The trial included 200 subfertile couples who were undergoing ART treatment for male factor subfertility. PARTICIPANTS/MATERIALS SETTING METHODS: Couples were randomized into treatment arm (n = 100) and control arm (n = 100). In the treatment arm, the male partner received oral antioxidants (Vitamin C, Vitamin E and Zinc) for 3 months just prior to the ART cycle. In the control arm, no antioxidant was given to the male partner. The primary outcome was clinical pregnancy rate, while live birth rate (LBR), miscarriage rate and changes in semen parameters were the secondary outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 200 women randomized, 135 underwent embryo transfer as per protocol. Following intention to treat analysis, no significant difference was noted in clinical pregnancy (36/100, 36% vs 26/100, 26%; odds ratio (OR) 1.60, 95% CI 0.87 to 2.93) and LBR (25/100, 25% vs 22/100, 22%; OR 1.18, 95% CI 0.61 to 2.27) between antioxidant and no pretreatment arms. The clinical pregnancy rate per embryo transfer was significantly higher following antioxidant pretreatment (35/64, 54.7% vs 26/71, 36.6%; OR 2.09, 95% CI 1.05 to 4.16) compared to no pretreatment. There was no significant difference in LBR per embryo transfer (25/64, 39.1%, vs 22/71, 31.0%; OR 1.43, 95% CI 0.70 to 2.91) after antioxidant pretreatment versus no pretreatment. The semen parameters of sperm concentration (median, interquartile range, IQR) (18.2, 8.6 to 37.5 vs 20.5, 8.0 to 52.5, million/ml; P = 0.97), motility (median, IQR) (34, 20 to 45 vs 31, 18 to 45%; P = 0.38) and morphology (mean ± SD) (2.0 ± 1.4 vs 2.2 ± 1.5%; P = 0.69) did not show any significant improvement after intake of antioxidant compared to no treatment, respectively. LIMITATIONS REASONS FOR CAUTION: The objective assessment of sperm DNA damage was not carried out before and after the antioxidant pretreatment. Since the clinicians were aware of the group allotment, performance bias cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: The current study did not show any significant difference in clinical pregnancy and LBR following antioxidant pretreatment for the male partner in couples undergoing ART for male subfertility. The findings need further validation in a larger placebo-controlled randomized trial. STUDY FUNDING/COMPETING INTERESTS: This trial has been funded by Fluid Research grant of Christian Medical College, Vellore (internal funding). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: CTRI/2013/02/003431. TRIAL REGISTRATION DATE: 26 February 2013. DATE OF FIRST PATIENT'S ENROLMENT: 11 February 2013.

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.