Effectiveness of GnRH Agonist Short Protocol Versus GnRH Antagonist Protocol in POSEIDON Groups 3 and 4: a Retrospective Cohort Study.

The aim of this study is to compare the ART (assisted reproductive technology) outcomes and cancellation rates between GnRH antagonist protocol and GnRH agonist short protocol in POSEIDON (Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number) groups 3 and 4. It is a retrospective cohort study conducted in the Department of Reproductive Medicine and Surgery of a tertiary-level hospital. Women who underwent ART treatment with either GnRH antagonist or GnRH agonist short protocol with fresh embryo transfer, between January 2012 and December 2019 belonging to POSEIDON 3 and 4 groups, were included. Among the 295 women who belonged to the POSEIDON groups 3 or 4, 138 women received GnRH antagonist and 157 women received GnRH agonist short protocol. The median total dose of gonadotropin in the GnRH antagonist protocol was not significantly different from GnRH agonist short protocol [3000, IQR (2481-3675) vs. 3175, IQR (2643-3993), p = 0.370]. There was a significant difference in the duration of stimulation between the GnRH antagonist and GnRH agonist short protocol [10, IQR (9-12) vs. 10, IQR (8-11), p = 0.002]. The median number of mature oocytes retrieved was significantly different in the cohort of women receiving GnRH antagonist protocol compared to GnRH agonist short protocol [3, IQR (2-5) vs. 3, IQR (2-4), p = 0.029]. There was no significant difference in the clinical pregnancy rate (24% vs. 20%, p = 0.503) and cycle cancellation rate (29.7% vs. 36.3%, p = 0.290) between the GnRH antagonist and agonist short protocols respectively. Live birth rate was not significantly different between the GnRH antagonist protocol (16.7%) and GnRH agonist short protocol (14.0%) [OR 1.23, 95% CI (0.56-2.68), p = 0.604]. After adjusting for the significant confounding factors, the live birth rate was not significantly associated with the antagonist protocol compared with the short protocol [aOR 1.08, 95% CI (0.44-2.63), p = 0.870]. Though GnRH antagonist protocol results in higher mature oocyte yield when compared with GnRH agonist short protocol, it does not translate into an increase in live birth in POSEIDON groups 3 and 4.

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.

POSEIDON classification and the proposed treatment options for groups 1 and 2: time to revisit? A retrospective analysis of 1425 ART cycles.

STUDY QUESTION: Do live birth outcomes differ when Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) stratified groups are compared with women with good prognosis (non-POSEIDON group) undergoing ART? SUMMARY ANSWER: The current study showed no significant difference in the live birth rates (LBRs) per embryo transfer between POSEIDON groups 1 and 2 when compared with women in the non-POSEIDON group undergoing ART. WHAT IS KNOWN ALREADY: Recently, there has been a lot of focus on the POSEIDON classification for low prognosis women undergoing ART and various management options have been advocated. For POSEIDON groups 1 and 2, low starting dose and gonadotrophin receptor polymorphism have been suggested as possible reasons for a hyporesponse, and increasing the starting gonadotrophin dose, the addition of recombinant LH and dual stimulation have been suggested as treatment options. Most of these treatment options are hypothetical in nature and need validation. STUDY DESIGN SIZE DURATION: In the current cohort study, a total of 1425 cycles were analyzed retrospectively following a single cycle fresh embryo transfer. The study period was from January 2013 to June 2018. PARTICIPANTS/MATERIALS SETTING METHODS: Women undergoing ART at a tertiary level infertility clinic were included. Clinical and treatment-related details were obtained from the hospital's electronic medical records. The ART outcomes in a non-POSEIDON group (women with an adequate ovarian reserve and/or optimal ovarian response i.e. >9 oocytes retrieved in the previous ART cycle) and a low prognosis group stratified by POSEIDON criteria were compared. We also examined the effectiveness of the modifications made in the current ART treatment protocols among women with an adequate ovarian reserve who had a history of poor/suboptimal response (POSEIDON 1 and 2). MAIN RESULTS AND THE ROLE OF CHANCE: There was no statistically significant difference in the LBR per embryo transfer in POSEIDON group 1 (32/109, 29%) and group 2 (17/58, 29%) when compared with the non-POSEIDON group (340/1041, 33%) (adjusted odds ratio (aOR) 0.69; 95% CI 0.37-1.27 and aOR 0.93, 95% CI 0.43-1.97, respectively), while significantly lower LBR were observed in POSEIDON groups 3 (17/97, 17.5%) and 4 (12/120, 10%) (aOR 0.49; 95% CI 0.28-0.89 and aOR 0.38, 95% CI 0.19-0.74, respectively). The gonadotrophin dose alone was increased in one-quarter of the cycles and in another 27% the dose was increased along with the protocol change among POSEIDON group 1. In POSEIDON group 2, a change in the dose alone and in combination with protocol change was performed in 5 and 41% of cycles, respectively. LIMITATIONS REASONS FOR CAUTION: A limitation of our study is the retrospective nature of the study with an inherent risk of unknown confounders influencing the outcomes. Other limitations are the lack of cumulative live birth data and the relatively small sample within POSEIDON group 2, which could lead to a type II error. WIDER IMPLICATIONS OF THE FINDINGS: The current study showed no significant difference in the LBR between the POSEIDON groups 1 and 2 when compared with the non-POSEIDON group of women, while groups 3 and 4 had significantly lower LBR. The simple gonadotrophin/protocol changes in groups 1 and 2 resulted in LBRs comparable to women with good prognosis. These findings call for revisiting the proposed treatment strategies for POSEIDON groups 1 and 2. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained. There are no competing interests to declare.

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.

Role of Hysterosalpingography in Diagnosing Tubal Blockage - A Prospective Diagnostic Study.

BACKGROUND: Women with abnormal hysterosalpingography (HSG) are anxious regarding the presence of tubal pathology. It is important to know the predictive value of HSG and the need for subsequent laparoscopy following an abnormal report. In the era of assisted reproductive technology, the role of invasive testing such as diagnostic laparoscopy is being increasingly questioned due to its invasiveness and associated risks. There is a need to explore the positive predictive value (PPV) of HSG in detecting bilateral tubal block in our population as PPV changes with the prevalence of disease. AIM: The aim of this study was to evaluate the diagnostic accuracy of HSG in identifying tubal blockage in subfertile women. SETTING AND DESIGN: This was a prospective diagnostic study conducted in the department of reproductive medicine and surgery in a university-level hospital. MATERIALS AND METHODS: The study included 199 subfertile women who had undergone HSG earlier and were planned for laparoscopy from April 2017 to January 2021. Findings of HSG and laparoscopy were compared with HSG as index test and laparoscopy as reference test, and the outcomes analysed were PPV of HSG for a bilateral tubal block, bilateral hydrosalpinx, abnormal HSG (unilateral or bilateral tubal block) and agreement between HSG and diagnostic laparoscopy in detecting normal and abnormal findings. STATISTICAL ANALYSIS: Kappa statistics, Stuart-Maxwell tests of marginal homogeneity and prevalence-adjusted bias-adjusted kappa (PABAK) statistics were used. RESULTS: The PPV for a bilateral block with HSG was 20.9% (95% CI: 13.7-29.7). The PPV of HSG for bilateral hydrosalpinx was 50.0% (95% CI: 6.8-93.2). PABAK was estimated to be 0.42 (95% CI: 0.30-0.55), suggestive of moderate agreement between the tests. Findings of laparoscopy in women with at least one patent tube in HSG showed that in 12.3% of cases, the management was likely to change due to the operative findings. CONCLUSION: The current study showed low PPV for bilateral tubal block diagnosed with HSG which translates into a need for further confirmation by laparoscopy. In one out of every eight women with at least one patent tube on HSG, performing laparoscopy changed the management.

Revisiting the role of serum progesterone as a test of ovulation in eumenorrheic subfertile women: a prospective diagnostic accuracy study.

OBJECTIVE: To estimate the prevalence of ovulatory cycles in eumenorrheic subfertile women and compare the diagnostic accuracy of a single ultrasound with serum midluteal progesterone measurement in detecting ovulatory cycles. DESIGN: Prospective diagnostic accuracy study. SETTING: University-level hospital. PATIENT(S): A total of 208 subfertile eumenorrheic women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): To estimate the prevalence of ovulatory cycles in eumenorrheic women and compare the diagnostic accuracy of a single, well-timed ultrasound scan (index test) with serum progesterone measurement (reference test) by calculating the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive likelihood ratio (LR+) and negative likelihood ratio (LR-). RESULT(S): The prevalence of ovulatory cycles among subfertile eumenorrheic women was 92.9% and 99.5% when midluteal serum progesterone level and ultrasound scanning were used as the reference test, respectively. The sensitivity, specificity, PPV, and NPV of ultrasound in identifying ovulatory cycles were 100%, 7.1%, 93.4%, and 100%, respectively. The LR+ and LR- were 1.1 and 0, respectively. The agreement between the ultrasound and serum progesterone was almost perfect (prevalence and bias-adjusted kappa = 0.81. CONCLUSION(S): The prevalence of ovulatory cycles in eumenorrheic subfertile women appears to be high. A single well-timed ultrasound can be performed to identify ovulatory cycles during the infertility workup in eumenorrheic women.

Perinatal Outcomes Following Assisted Reproductive Technology.

As the use of routine assisted reproductive technology (ART) becomes widespread along with the extended applications such as ART with donor gametes, surrogacy, and preimplantation genetic testing (PGT), it becomes more pertinent to evaluate risks associated with them. Perinatal outcomes and long-term safety for the women and children are paramount. In this review, we aimed to detail the perinatal outcomes in relation to the ART procedures routinely applied as the extended applications of ART with a focus on singleton pregnancies. While there seems to be a higher risk of adverse perinatal outcomes with some of the ART procedures, the absolute risk increase is generally low. It is important for clinicians to have this knowledge to better counsel and care for their patients.