Inter-cycle variability of anti-Müllerian hormone: implications for predicting controlled ovarian stimulation cycle outcomes.

BACKGROUND: Anti-Müllerian hormone (AMH) is a widely used marker for estimating ovarian reserve, and it may predict response to ovarian stimulation. While AMH is considered a stable, cycle-independent marker, studies have shown it can exhibit significant fluctuations based on factors like age, reproductive stage, and menstrual cycle phase. The fluctuations in AMH levels can make it challenging to predict individual responses accurately, particularly when the AMH is not measured in the COS cycle. The aim of this study was to assess the inter-cycle variability of serum AMH levels in two consecutive menstrual cycles and their correlation with response to controlled ovarian stimulation outcome in the latter. METHODS: In this single-centre retrospective cohort study, data of normal and low responder patients who underwent intracytoplasmic sperm injection following a GnRH antagonist cycle at a university hospital infertility clinic between January 2022 and December 2023 were reviewed. Serum AMH levels were measured in the early follicular phase of two consecutive menstrual cycles with Elecsys-AMH Roche® system (Roche Diagnostics, Meylan, France). Correlations between AMH levels and controlled ovarian stimulation outcomes, including total oocyte and mature oocyte (MII) counts, were assessed. The study included normal and poor responder women to maintain data integrity. RESULTS: A total of 79 patients were included in the final analyses. Significant cycle-to-cycle variation in serum AMH levels was observed, with a median variation of 44.3%. Normal responders exhibited a mean change of 0.60 ± 0.46 ng/ml, while poor responders had a mean change of 0.28 ± 0.28 ng/ml. Approximately 20% of patients were reclassified between normal and poor responder categories based on the second AMH measurement. The controlled ovarian stimulation cycle AMH levels showed a stronger correlation with both total oocyte count (r = 0.871, P < 0.001) and MII oocyte count (r = 0.820, P < 0.001) compared to preceding cycle AMH levels. CONCLUSION: AMH levels can exhibit significant variations between consecutive cycles, potentially leading to misclassification of patients. Measuring AMH in the early follicular phase of the COS cycle provides a more accurate prediction of the numbers of total and MII oocytes collected. Consistent and repeated AMH measurements can help clinical decision-making.

Proposal for Diagnostic Criteria of Y-Shaped Dysmorphic Uterus Based on 3-Dimensional Transvaginal Ultrasound Measurements.

STUDY OBJECTIVE: To define objective and readily applied diagnostic criteria for Y-shaped uteri using 3-dimensional transvaginal ultrasound (3D-TVUS) volume recordings. DESIGN: A retrospective case-control diagnostic measurements study. SETTING: A tertiary university hospital's reproductive health and research center. PATIENTS: Two hundred thirteen patients who presented with infertility between January 2020 and December 2022. INTERVENTIONS: Two blinded physicians re-evaluated the 3D-TVUS images of all patients for the presence of a uterine abnormality. The images of patients with a Y-shaped uterus were re-evaluated, and descriptive measurements were done. MEASUREMENTS AND MAIN RESULTS: The most common uterine abnormality in this cohort was the Y-shaped uterus with a prevalence of 12.2%, followed by the arcuate, T-shaped, and septate uteri, respectively. Reviewers identified 26 and 28 Y-shaped uteri, respectively, and came to a consensus on 25 images. Diagnostic criteria for the Y-shaped uterus based on 3D-TVUS findings have been specified as: lateral indentation depths between 4 and 7 mm, fundal indentation depth between 5 and 9 mm, lateral indentation angles between 121° and 149°, fundal indentation angle between 121° and 145°, and Y-angles 25° to 46°. CONCLUSION: Some subtypes of dysmorphic uteri, such as the Y-shaped uterus, whose clinical significance is unknown and may be variants of the normal, may actually be more common than thought. Determining objective diagnostic criteria with 3D-TVUS will allow standard research on these anomalies and their clinical significance.

Evaluation of the Impact of Letrozole in Combination with the GnRH Antagonist Ovarian Stimulation Protocol in Patients Expected to Have a Poor Ovarian Response (POSEIDON Groups 3 and 4).

Background and Objectives: The objective of this study was to evaluate the impact of adjuvant letrozole administration during ovarian stimulation using the gonadotropin-releasing hormone (GnRH) antagonist protocol on treatment outcomes in women categorized into POSEIDON groups 3 and 4. Materials and Methods: This retrospective cohort study analyzed data from patients classified into POSEIDON groups 3 and 4 who underwent fresh embryo transfer subsequent to intracytoplasmic sperm injection following a GnRH antagonist stimulation protocol between January 2017 and December 2021. Patients were divided into two groups: the GnRH-LZ group, who received letrozole at a dosage of 5 mg/day for five consecutive days, and the GnRH-ant group, who did not receive adjuvant letrozole. The primary outcome measure of the study was a comparative analysis of live birth rates between the two groups. Results: A total of 449 patients were deemed suitable for final analysis and were allocated into two groups: 281 patients in the GnRH-ant group and 168 patients in the GnRH-LZ group. Live birth rates were found to be comparable in both groups (11% vs. 9%, p = 0.497). Letrozole administration significantly reduced the total amount of gonadotropins required (2606.2 ± 1284.5 vs. 3097.8 ± 1073.3, p < 0.001), the duration of ovarian stimulation (11.2 ± 3.9 vs. 10.2 ± 3, p = 0.005), and the serum peak estradiol concentration (901.4 ± 599.6 vs. 463.8 ± 312.3, p < 0.001). Conclusions: Adjuvant letrozole administration did not demonstrate a significant impact on live birth rates among women categorized into POSEIDON groups 3 and 4. However, this approach may offer potential cost reductions by diminishing the necessity for exogenous gonadotropins and shortening the duration of ovarian stimulation.

The size, number and bilaterality of endometriomas do not affect spontaneous conception chance following surgical removal.

OBJECTIVE: Endometrioma surgery is associated with a reduction in ovarian reserve. However, removal of an endometrioma may increase the likelihood of a spontaneous conception. The objective of this study was to assess the pre-operative and operative variables affecting spontaneous conception following endometrioma surgery. METHODS: Data from 211 women ≤40 years of age who underwent an endometrioma surgery at a university-based infertility clinic between January 2005 and June 2020 were reviewed retrospectively. The main outcome measure was spontaneous clinical pregnancy. We had 84 women with and 127 women without a successful spontaneous conception making up the case and control groups. RESULTS: The median ages of the cases and controls were 27 and 32 years, respectively (p<0.001). The rate of recurrence was significantly lower in the spontaneous conception group when compared to controls (29.8% vs. 52.8%, respectively; p=0.001). Our results showed no differences in the number, size, or side of the endometriomas in both groups. Multivariate logistic regression analysis showed significant independent effects of age (B: -.166, OR {odds ratio}: 0.847, 95% CI {confidence interval}: 0.791-0.907, p<0.001), recurrence (B: -1.030, OR: 0.357, 95% CI: 0.188-0.678, p=0.002), and laparoscopic surgery rather than laparotomy (B: 1.585, OR: 4.879, 95% CI: 1.029-23.133, p=0.046) for spontaneous conception. CONCLUSIONS: The size, number and bilaterality of the endometrioma did not affect the spontaneous conception likelihood following surgical removal. However, increasing age and recurrence are negatively associated with the likelihood of spontaneous conception. Laparoscopic surgery may increase the chance of spontaneous conception when compared to laparotomy.

Laparoscopy versus open surgery for the surgical management of tubo-ovarian abscess (TOA). Is there a beneficial impact of early endoscopic intervention in terms of fertility rates?

OBJECTIVES: To compare success rates and complications in women undergoing laparoscopic versus open surgical management of tubo-ovarian abscess. We further examined whether early laparoscopic intervention has any impact on pregnancy rates in a subgroup of infertile patients following frozen-thawed embryo transfer. MATERIAL AND METHODS: Hospital records of 48 patients diagnosed with TOA between January 2015 and December 2020, who underwent surgical intervention or received only medical treatment were analyzed. All patients were hospitalized, and parenteral antibiotics were commenced on admission initially. Laparoscopic or open surgery was performed within 48 hours course of intravenous antibiotherapy (early intervention) or later according to the clinical findings and antibiotherapy response. RESULTS: Of 48 patients with TOA, 18 (37.5%) underwent laparoscopic and 30 (62.5%) underwent open surgical intervention. The median postoperative hospital stay was shorter (4.5 days vs 7.5 days, respectively; p = 0.035), and postoperative opioid analgesic requirement was lesser in the laparoscopy group compared to open surgery group (22% vs 53%, respectively; p = 0.034). Intra- and post-operative complication rates were similar between the groups. Of these 48 patients, seven were diagnosed to have TOA following oocyte retrieval, and four of these conceived with frozen thawed embryo transfer all of whom underwent laparoscopic surgery within 48 hours of diagnosis. CONCLUSIONS: Minimal invasive surgery should be preferred even in the presence of severely adhesive and inflammatory TOA in order to improve postoperative outcomes. Moreover, early laparoscopic intervention may be considered in infertile patients with an aim to optimize pregnancy rates in a subsequent frozen-thawed embryo transfer.

Presence of Endometrioma Does Not Impair Embryo Quality and Assisted Reproductive Technology (ART) Cycle Outcome in Diminished Ovarian Reserve (DOR) Patients.

This study aims to assess the impact of endometrioma on embryo quality and cycle outcome in patients who undergo assisted reproductive technology (ART) treatment due to diminished ovarian reserve (DOR). Retrospective case-control study was conducted in women ≤ 40 years of age who underwent ART treatment caused by DOR, defined according to POSEIDON criteria, at a university-based infertility clinic between January 2015 and December 2020. Three groups of patients were selected: group A included patients with an idiopathic DOR, group B included patients with endometrioma(s) who underwent ovarian cystectomy, and group C included patients with endometrioma(s) without surgical treatment. A total of 351 women with DOR were included in the final analysis. Demographic characteristics, including age and AMH, were similar between the groups. Significant differences were observed among groups on mean number of MII oocytes retrieved (1.88 ± 1.59 vs. 2.84 ± 2.89 vs. 2.78 ± 2.41, respectively; p < 0.001) and mean number of embryos (1.04 ± 1.18 vs. 1.87 ± 2.01 vs. 1.66 ± 1.81, respectively; p < 0.001). However, the mean number of top-quality embryos, cycle cancellation, and live birth rates were similar between the groups. Clinical pregnancy (35 (26.5%) vs. 8 (18.2%) vs. 18 (42.9%), respectively; p = 0.038) and miscarriage rates (12 (9.1%) vs. 0 vs. 8 (19.0%), respectively; p = 0.009) were higher in endometrioma group without surgery. Women with DOR appear to have similar ART cycle outcomes regardless of the etiology, in terms of live birth rates. Infertility of endometrioma patients might be related to altered endometrium rather than to decreased oocyte quality. Cystectomy for endometrioma before IVF did not seem to affect the LBR.

Impact of an estrogen replacement regimen on live birth rate in frozen-thawed good-quality embryo transfer.

OBJECTIVE: To assess the impact of an estrogen replacement regimen on frozen embryo transfer (FET) cycle outcome. METHODS: In the present retrospective cohort study, data of infertile women undergoing FET with good-quality embryos were reviewed. The first group received 2 mg of estradiol hemihydrate (EH) once daily for 6 to 7 days, then twice daily for 4 to 5 days, and then three times a day until embryo transfer. The second group received EH twice daily for 7 to 8 days, then three times a day. The third group received EH three times a day constantly. The main outcome measure was live birth rate. RESULTS: In total, 394 FET cycles were included. The fixed 6-mg group required the highest estradiol hemihydrate dose. The duration of estrogen treatment was significantly longer in the first group. Maximal endometrial thickness was highest in the second group (10.2 ± 1.3 mm vs. 9.6 ± 1.4 mm vs. 8.6 ± 0.9 mm, respectively; P < 0.001). The clinical pregnancy rates in the groups were 41.1%, 55.2%, and 42.2%, respectively (P = 0.035). Live birth rates were 40.8%, 50.9%, and 48.1%, respectively (P = 0.320). CONCLUSION: In FET cycles with hormone replacement therapy, a step-up 4-mg regimen provides thicker endometrium with optimal-dose estrogen in an adequate time frame. The tendency for increased clinical pregnancy and live birth rates is remarkable.

Endometrial compaction is associated with the increased live birth rate in artificial frozen-thawed embryo transfer cycles.

We aimed to assess the effect of endometrial compaction on the live birth rate in frozen-thawed embryo transfer (FET) cycles and to investigate the parameters associated with compaction. FET cycles performed in a tertiary care infertility centre between May 2013 and October 2019 were reviewed retrospectively. The decremental change of endometrial thickness between the end of oestrogen phase and ET day was defined as endometrial compaction. The primary outcome measure was endometrial compaction, and the secondary outcome was the live birth rate. Among all, 89 had endometrial compaction and 194 did not. The live birth rate was significantly higher in the compaction group (23.6 vs. 13.4%, respectively; p = 0.039). Multivariate logistic regression analysis revealed that in FET cycles with artificial endometrial preparation, the chance for live birth was significantly higher in cycles with endometrial compaction [OR: 3.133, 95% confidence interval (CI) 1.104-8.892; p = 0.032] when adjusted for age, stage of the embryo, and endometrial thickness at the end of the oestrogen phase. According to receiver operating characteristic (ROC) curve analysis the sensitivity and specificity of 9.25 mm endometrial thickness at the end of oestrogen phase were 76.4 and 58.8%, respectively (area under the curve: 0.701, 95% CI 0.640-0.763; p < 0.001) to predict endometrial compaction.

Longitudinal change in serum inflammatory markers in women with tubo-ovarian abscess after successful surgical treatment: a retrospective study.

High levels of serum inflammatory markers are related to extended hospitalisation and more severe disease in the case of tubo-ovarian abscess (TOA). There is scarce information on the serial measurement of inflammatory markers during the postoperative follow-up period of surgically treated TOA. The present study aimed to assess the postoperative longitudinal changes in serum inflammatory markers following surgery for TOA. In this retrospective cohort study, patients who underwent surgery for TOA between January 2010 and March 2020 were reviewed. All inflammatory markers peaked within 48 hours after surgical intervention and then declined with time. The predicted mean of white blood cell count (WBC) to return to normal was 2.5 days (95% CI: 1.0-4.3), which was followed by neutrophil to lymphocyte ratio (NLR) (7.1 days, 95% CI: 4.7-10.8) and C-reactive protein (CRP) (+14 days). In conclusion, serum inflammatory markers increase in the very early post-operative period. While the normalisation period is very slow, it may not be appropriate to use CRP for evaluating the treatment success of TOA surgery. However, WBC and NLR measurements might be useful for follow-up and predicting the need for medical or surgical intervention.Impact statementWhat is already known on this subject? Serum inflammatory markers such as C-reactive protein, white blood cell count, and neutrophil to lymphocyte ratio are usually elevated in women with tubo-ovairan abscess, and high levels of these markers are associated with extended hospitalisation and more severe disease.What do the results of this study add? Our results indicate that the serum inflammatory markers increase and peak within the first 48 hours after surgery for tubo-ovarian abscess. Normalisation of white blood cell count is the fastest in successfully treated patients. However, normalisation of C-reactive protein is slowest, reaching 14 days and might not be as feasible as white blood cell count and neutrophil to lymphocyte ratio in postoperative patient follow-up.What are the implications of these findings for clinical practice and further research? The serum inflammatory markers should be interpreted with caution within 48 hours after surgical treatment for tubo-ovarian abscess. Instead of C-reactive protein white blood cell count, and neutrophil to lymphocyte ratio measurements can be preferred in post-operative follow-up to predict the need for further medical or surgical intervention.

Intrauterine insemination with ovarian stimulation is a successful step prior to assisted reproductive technology for couples with unexplained infertility.

The present retrospective cohort study analysed data of couples with unexplained infertility who underwent two to three intrauterine insemination (IUI) cycles. The inclusion criteria were age 20-40 years, failure to conceive for at least two years of unprotected intercourse, ovulation, normal semen analysis, and tubal patency. Total of 578 IUI cycles of 286 couples with unexplained infertility were included in the final analyses. The mean age and duration of infertility of the study population were 28.8 ± 5.1 and 5.2 ± 3.4 years, respectively. The clinical pregnancy rate (CPR) and live birth rate (LBR) per cycle were 16.6 and 13.1%, respectively. The cumulative CPR following two to three IUI cycles was 33.5% and the cumulative LBR was 26.5% for the entire cohort. The duration of infertility was significantly shorter in women whose IUI attempt were successful (p = .036). Up to three cycles of IUI with ovarian stimulation seems as an effective first-line treatment modality in unexplained infertility.IMPACT STATEMENTWhat is already known on this subject? Cont rolled ovarian stimulation combined with intrauterine insemination (IUI) is a common infertility treatment as a low-cost, less-invasive alternative to in vitro fertilisation (IVF) and was approved as a first line treatment option for unexplained infertility However, the UK National Institute for Health and Care Excellence (NICE) guideline states that IUI is not recommended to couples with unexplained infertility, male factor and mild endometriosis, unless the couples have religious, cultural or social objections to proceed with IVF.What do the results of this study add? Up to three IUI cycles with ovarian stimulation can be considered as an effective treatment modality in unexplained infertility even in couples who could not achieve pregnancy by expectant management for two years.What are the implications of these findings for clinical practice and/or further research? The clinicians should reconsider the NICE recommendation of IVF in the light of recent studies including ours which recommend IUI together when dealing couples with unexplained infertility.

A Feasible Option before Cycle Cancellation for Poor Responders; STOP-START Protocol.

Despite the advances in controlled ovarian stimulation (COS), management of a subgroup of poor ovarian responder patients may still be challenging. We describe a feasible and simplified protocol, namely the STOP-START protocol, for poor responders defined as Patient-Oriented Strategies Encompassing Individualize D Oocyte Number (POSEIDON) groups 3 and 4, who are unresponsive to COS with maximum dose gonadotrophins. Data of 11 women unresponsive to COS were reviewed. Mean age of the patients was 36.5 ± 6.0 years. Unresponsiveness was defined as no follicular growth >9 mm and/or estradiol level less than 40 pg/ml after a week of recombinant follicle stimulating hormone (rFSH, 225-300 IU) administration. In that case, COS was stopped and each woman underwent weekly ultrasound assessment to catch a secondary follicular growth. All women showed at least one follicular growth within five to 20 days. Six women (54.5%) had spontaneous follicular growth and the other five required ovarian stimulation. At least one oocyte was retrieved from each one of seven patients (63.6%). The mean number of oocytes retrieved was 1.6 ± 1.4 and five women (45.5%) had at least one grade A embryo. Among all, two women became pregnant successfully and both gave live births (18.2%). In conclusion, STOP-START protocol may potentially be an effective, feasible, and time-saving management option for POSEIDON group 3/4 poor responders who are unresponsive to standard COS treatment with maximum dose gonadotrophins.

Anorexigenic peptide (leptin, obestatin, nesfatin-1) levels and their impact on assisted reproductive technology treatment outcomes in patients with polycystic ovary syndrome.

OBJECTIVE: In this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes. METHODS: A prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses. RESULTS: In the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients. CONCLUSION: Baseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS. This possibility should be confirmed in further research.

Factors associated with livebirth in couples undergoing their first in vitro fertilization cycle: An internally validated prediction model

Objective: The aim of the study is to create a new model to predict successful outcome in assisted reproductive techniques. Materials and Methods: A retrospective cohort study was conducted in tertiary fertility center between 2010 and 2017. Nulliparous women younger than 45 years-old undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for the first time were included; frozen embryo transfers, canceled induction cycles, freeze-all cycles were excluded. Two prediction models were built using multivariate logistic regression with a subset of the dataset and then were internally validated using bootstrapping methods. Results: Four hundred eighty eight women were included with 136 (27.9%) live births. The basal model was built using variable age, antral follicle count (AFC), and basal luteinizing hormone (LH) levels. Age over 37 years [odds ratio (OR): 0.07, 95% confidence interval (CI): 0.00-0.36] and AFC below 5 (OR: 0.15, 95% CI: 0.02-0.53) was associated with poorer outcomes whereas an LH level above 6 mIU/mL (OR: 2.24, 95% CI: 1.27-3.94) was associated with better outcomes. Optimism adjusted area under the curve (AUC) of this model was 0.68 (95% CI: 0.62-0.74). Combined model in addition to basal model variables included the length of induction cycle, the endometrial thickness at the day of transfer, grade and count of the transferred embryo. Cycles lasting more than ten days (OR: 2.23, 95% CI: 1.17-4.42), an endometrial thickness greater than 9 mm (OR: 2.07, 95% CI: 1.00-4.53) were associated with better outcomes. Optimism adjusted AUC of this model was 0.76 (95% CI: 0.70-0.81). Calibration of both models was good according to Hosmer Lemeshow test (p=0.979 and p=0.848, respectively). Conclusion: This internally validated prediction model has good calibration and can be used predicting outcomes in first time IVF/ICSI cycles with modest sensitivity.

hCG day progesterone level has no impact on the frozen thawed embryo transfer cycle outcome.

OBJECTIVE: To assess the association between hCG day progesterone levels and subsequent frozen-thawed embryo transfer (FET) cycle outcome in infertile women with and without polycystic ovary syndrome (PCOS). METHOD: Data of 178 women who underwent FET at a university-based infertility clinic between January 2016 and December 2019 were reviewed. The study group consisted of women who had progesterone elevation (PE) during fresh controlled ovarian stimulation (COS) cycle. A sub-group analysis was also performed in PCOS and non-PCOS patients. RESULTS: There were no differences in clinical pregnancy (47.7 % vs. 50.7 %, p = 0.729), miscarriage (15.9 % vs. 22.4 %, p = 0.359), and live birth rates (27.3 % vs. 23.9 %, p = 0.652) following FET between women with and without PE in the fresh cycle. The results remained non-significant regarding the clinical pregnancy (46.7 % vs. 53.4 %, p = 0.549), miscarriage (13.3 % vs. 27.6 %, p = 0.133), and live birth rates (26.7 % vs. 19.0 %, p = 0.408) in participants with PCOS (n = 88). CONCLUSION: hCG day progesterone level in the fresh COS cycle does not have a significant impact on the subsequent FET cycle neither in PCOS nor in non-PCOS women.

Clomiphene Citrate versus Recombinant FSH in intrauterine insemination cycles with mono- or bi-follicular development.

OBJECTIVE: The present study aims to assess the success of controlled ovarian stimulation in intrauterine insemination cycles stimulated by recombinant-FSH and Clomiphene citrate for either mono- or bi-follicular development. METHODS: We assessed 870 infertile patients treated with controlled ovarian stimulation in intrauterine insemination cycles at a university-based infertility clinic between January 2012 and December 2017. We compared the cycles stimulated by clomiphene citrate and recombinant-FSH in two set-ups; mono- and bi-follicular development. The main outcome measure was the clinical pregnancy rate per cycle. RESULTS: The demographic and cycle parameters were similar between the groups, except for endometrial thickness on the day of hCG administration, which was higher in the recombinant-FSH group than the clomiphene citrate group. The overall clinical pregnancy rates in clomiphene citrate and recombinant-FSH groups were 9.8% and 10.3%, respectively (p=0.940). Regarding the entire cohort, clinical pregnancy was significantly higher in cases of bi-follicular development when compared to mono-follicular development (16.8% vs. 10.2%, respectively; p=0.009). CONCLUSIONS: Clomiphene citrate and recombinant-FSH have similar success rates in terms of clinical pregnancy, in either mono-follicular development or bi-follicular development. Clomiphene citrate and recombinant-FSH cycles resulted in comparable rates of bi-follicular development, which significantly increases clinical pregnancy rate. Clomiphene citrate and recombinant-FSH have similar success rates in terms of clinical pregnancy, in either mono-follicular development or bi-follicular development.

Comparison of Oocyte and Embryo Quality Between Random Start and Controlled Ovarian Stimulation Cycles in Cancer Patients Undergoing Fertility Preservation.

Conventional assisted reproductive technology (ART) cycles may delay cancer treatment and compromise survival, and also increase patients' psychological burden as a result of delayed chemotherapy. The aim of this study was to compare the success rates of random start and conventional start GnRH antagonist protocols in terms of oocyte and embryo outputs in cancer patients. Data of 111 patients with a newly diagnosed cancer who underwent ART for fertility preservation at a university-based infertility clinic between January 2010 and September 2019 were reviewed. The study group underwent random start controlled ovarian hyperstimulation (RS-COH) and the control group underwent conventional start COH (CS-COH). The main outcome measures were the number of total oocytes, MII oocytes, and embryo yield. A total of 46 patients (41.5%) underwent RS-COH and 65 (58.5%) underwent CS-COH. Baseline characteristics were similar between the groups. The most common cancer type in both groups was breast cancer (60.9% vs. 52.3%, respectively). The median duration of stimulation was significantly longer in RS-COH than in CS-COH (12 vs. 10 days; P = 0.005). The median number of MII oocytes was significantly higher in RS-COH than in CS-COH (7 vs. 5 oocytes, respectively; P = 0.020). The MII/AFC ratio was significantly higher in the RS-COH group compared to the CS-COH group (74% and 57% respectively; p = 0.02). In the linear regression analyses, RS-COH protocol did not have a significant impact on MII/AFC (standardized ß coefficient - 0.514; P = 0.289 {adjusted R2 for the model = 0.779}), oocyte yield (standardized ß coefficient - 0.070; P = 0.829 {adjusted R2 for the model = 0.840}), and MII rate (standardized ß coefficient - 0.504; P = 0.596 {adjusted R2 for the model = 0.271}). In conclusion, RS-COH protocol is as effective as CS-COH protocols for fertility preservation in cancer patients.

The efficacy of dydrogesterone use to suppress premature luteinizing hormone surge on cycle outcomes in controlled ovarian stimulation

Objective: Progestins are used as an alternative to gonadotropin releasing hormone (GnRH) antagonists to suppress premature luteinizing hormone (LH) surge and a flexible protocol has been defined recently. The aim of this study was to compare the efficacy of flexible protocols with dydrogesterone and GnRH antagonist in suppressing LH surge. Material and Methods: This retrospective, case-control study, was conducted in an infertility unit of a tertiary university hospital. A daily dose of 40 mg dydrogesterone was compared with GnRH antagonist (GnRHant) in controlled ovarian hyperstimulation cycles between July 2018 and July 2019. Dydrogesterone was started when the leading follicle was 12 mm or serum estradiol was over 300 pg/mL. A subgroup analysis of poor responder patients was also performed. Results: In total there were 105 subjects aged between 23 and 41 years, 52 in the dydrogesterone group and 53 in the GnRHant group. Duration of pituitary suppression was longer in dydrogesterone group. Premature ovulation was observed in 11.5% (6/52) and 0% in the dydrogesterone and GnRHant groups, respectively. However, collected oocyte counts and metaphase II oocyte counts were found to be similar between the groups. The six patients with premature ovulation were in poor responder subgroup. Conclusion: Dydrogesterone can be used as an alternative to antagonist regimen in patients where embryo transfer is not planned in the same cycle. However, flexible regimen may not be appropriate in patients with diminished ovarian reserve, as advanced follicular maturation and delayed suppressive effect of oral progesterone may cause premature ovulation. Randomized controlled trials in particular patient groups are required to determine the most effective minimum dose and time of application to ensure treatment success.

Endometrioma surgery is associated with increased risk of subsequent assisted reproductive technology cycle cancellation; a retrospective cohort study.

The aim of this study was to assess the effect of laparoscopic removal of endometrioma on assisted reproductive technology (ART) outcome. A retrospective cohort study was conducted at a university hospital between January 2014 and December 2017. The ART group consisted of 26 women who underwent 44 ART cycles in the presence of ovarian endometrioma and the surgery group consisted of 53 women who underwent 58 ART cycles after laparoscopic removal of ovarian endometrioma/s. There were no statistically significant differences between the groups regarding demographic parameters and background features including cycle parameters. The live birth rates in the ART and Surgery groups per embryo transfer were 23.7 and 26.1%, respectively (p = .800). The rate of cycle cancellation due to poor response and/or failed oocyte retrieval was significantly higher in the Surgery group than ART group (13.7 vs. 0%, respectively; p = .018). In conclusion, cystectomy significantly increases the risk of cycle cancellation due to poor ovarian response, which might be catastrophic individually. However, it does not seem to affect the live birth rates.IMPACT STATEMENTWhat is already known on this subject? Both the presence of an endometrioma or surgical removal may have deleterious effects on fertility potential.What do the results of this study add? Our results confirm that although cystectomy has no benefit on the number of oocytes collected and live birth rate, it increases the risk of cycle cancellation significantly in assisted reproductive technology cycles following endometrioma surgery.What are the implications of these findings for clinical practice and/or further research? Postponing cystectomy until a freeze-all cycle may be the best option to maximise the number of oocytes retrieved and to maximise the ovarian response.

Human Menopausal Gonadotropin Commenced on Early Follicular Period Increases Live Birth Rates in POSEIDON Group 3 and 4 Poor Responders.

Human menopausal gonadotropin (hMG) has LH activity, and it may have beneficial effects in terms of oocyte quality and endometrial receptivity similar to recombinant LH supplementation. The aim of this study was to assess the effects of hMG, and its commencement time on the outcome of assisted reproductive technology (ART) cycles of POSEIDON group 3 and 4 poor responders. Data of 558 POSEIDON group 3 and 4 poor responders who underwent ART treatment following a GnRH antagonist cycle at a university-based infertility clinic between January 2014 and December 2019 were reviewed. hMG was commenced at the early follicular phase or mid-follicular phase in the study groups. The control group did not receive hMG stimulation. Live birth rate (LBR) was the main outcome measure. The mean duration of stimulation was significantly shorter in early follicular hMG group than in mid-follicular hMG group (11.9 ± 3.6 days vs. 12.8 ± 4 days, respectively; P = 0.027). The mean numbers of oocytes retrieved and MII oocytes were comparable between the groups. The LBRs per embryo transfer in early follicular hMG, mid-follicular hMG, and control groups were 21.9%, 11.7%, and 11.6%, respectively (P = 0.035). In conclusion, there is a significant association between the commencement time of hMG and live birth chance in ART cycles of POSEIDON group 3 and 4 poor responders. Early initiation of hMG together with rFSH seems to be beneficial in this specific population.

The association between operative hysteroscopy prior to assisted reproductive technology and cervical insufficiency in second trimester.

PURPOSE: To assess the association between operative hysteroscopy prior to assisted reproductive technology (ART) cycle and cervical insufficiency (CI) in the second trimester of pregnancy. METHODS: A retrospective cohort study was conducted. The charts of all women who got pregnant following an ART cycle between January 2015 and June 2018 were reviewed. The study group consisted of pregnant women who underwent operative hysteroscopy within 6 months before conception. The control group consisted of pregnant women who did not undergo hysteroscopy or any type of cervical surgical procedure before conception. The primary outcome measure was CI during the second trimester (13-27 weeks of gestation). RESULTS: A total of 363 pregnancies achieved by ART cycles were assessed. After the exclusion of multiple pregnancies (n = 19), previous surgical procedures (n = 4) and first-trimester pregnancy losses (n = 80), there were 29 women in the study group and 231 women in the control group. The mean ages of the study and control groups were 31.2 ± 4.06 and 29.82 ± 4.71 years, respectively (P = 0.13). The indications for operative hysteroscopy were uterine septum (n = 19), T-shaped uterus (n = 4), endometrial polyp (n = 4), and submucosal fibroids (n = 2). The rates of CI in the study and control groups were 13.7% (4/29) and 3.4% (8/231), respectively (P = 0.012). The term delivery rates in the study and control groups were 79.3 and 91.8%, respectively (P = 0.044). CONCLUSIONS: Operative hysteroscopy prior to ART cycles is significantly associated with CI between 13 and 27 weeks of gestation. Further investigation with larger cohorts is urgently needed to clarify this issue.