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This guideline was prepared by the Turkish Society of Reproductive Medicine to define the conditions and requirements for an outsourced preimplantation genetic testing (PGT) programme in line with the experience and needs of practitioners. This guideline is intended to be a reference document for assisted reproductive technology centres, genetic diagnosis centres, non-governmental organizations working on reproductive health, legal experts, consultants working on laboratory accreditation, academicians specializing in ethical issues, and policy makers. The Consortium aims to provide recommendations addressing the challenges of genetic testing, especially PGT for monogenic diseases (PGT-M) due to the high rate of consanguineous marriage in Turkey. For this purpose, this summary document specifically includes challenges and recommendations regarding PGT-M practice, and aims to identify and aid in prevention of errors leading to misdiagnosis. The recommendations can be modified to fit other locations., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the potential ceiling effect of high serum progesterone levels on the day of embryo transfer for pregnancy outcomes in patients undergoing artificial frozen-thawed blastocyst transfer (FET) cycles., Materials and Methods: This retrospective cohort study included 595 patients who underwent artificial FET cycles. We evaluated progesterone levels and found that 40.6 ng/mL corresponded to the 90th percentile and 23.9 ng/mL corresponded to the 50th percentile. Based on these findings, we categorized progesterone levels as <20 ng/mL (n=220, 37.0%), 20-40 ng/mL (n=312, 52.4%), and ≥40 ng/mL (n=63, 10.6%). The primary outcome measures were the clinical pregnancy rate (CPR) and live birth rate (LBR)., Results: Blastocyst morphology grades, including expansion, trophectoderm, and inner cell mass grades, were significantly associated with clinical pregnancy (p<0.001 for all). Progesterone levels between 20 and 40 ng/mL were associated with higher CPR (p=0.043). In the multivariate analysis, only blastocyst expansion and inner cell mass grades were independently and significantly associated with CPR [p=0.011, odds ratio (OR)=1.6, (confidence interval) CI 95%=1.13-2.39, and p=0.007, OR=1.65, CI 95%=1.14-2.39, respectively]. The progesterone level and trophectoderm grade were not statistically significant. Regarding LBR, only blastocyst expansion grades 4 and trophectoderm grades A or B were significantly associated., Conclusion: Based on these data, we speculate that if serum progesterone levels exceed 40 ng/mL on the day of embryo transfer in patients undergoing artificial FET cycles, there is no need to reduce the progesterone dose., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright© 2024 The Author. Published by Galenos Publishing House on behalf of Turkish Society of Obstetrics and Gynecology.)

Purpose: The main purpose of this study is to compare the validity of transcervical embryoscopy method with standard uterine evacuation method in detecting more accurate karyotypes in miscarriages below tenth week of pregnancy. Additionally, the frequency and distribution of fetal morphological abnormality were evaluated., Methods: A prospective study was carried out at the Gazi University Faculty of Medicine, Department of Obstetrics and Gynecology. Patients with missed abortions between sixth and tenth gestational weeks were included in the study group, and fetal morphological examination and direct embryonic biopsy were performed by transcervical embryoscopy. The control group consisted of patients who experienced miscarriage and genetic material obtained from routine uterine evacuation between February and October 2023., Result: A total of 60 patients in the study group and 189 patients in the control group were evaluated. The median ages, previous miscarriage numbers, median gravida numbers, and median gestational weeks were comparable between groups. Chromosomal abnormality was detected in 24 (42.8%) and 52 embryos (29.9%) in the study and control groups, respectively (p = 0.004). Culture failure rates were 6.6% (n = 4) and 7.9% (n = 15) in the study and control groups, respectively. In the study group, 12 embryos had a morphological abnormality in which 6 of them had normal karyotype., Conclusion: Direct embryonic biopsy with transcervical embryoscopy is an effective method to exclude maternal decidual cell contamination and placental mosaicism in miscarriages for karyotype analysis. In addition, detecting anomalies in morphology might contribute our understanding in the process of miscarriages which arises independent from structural/numerical chromosomal abnormalities., (© 2024. The Author(s).)

Purpose: To provide technical guidance on applying catheter-directed and needle-directed ethanol sclerotherapy for endometriomas and present the results of these sclerotherapy methods., Materials and Methods: From January 2015 to March 2021, the results of the patients with symptomatic ovarian endometriomas who underwent needle-directed or catheter-directed sclerotherapy were evaluated, retrospectively. The decision to apply which sclerotherapy technique was made during the procedure for each patient considering the following factors: cyst size, cyst location, cyst viscosity, and tissue rigidity., Results: Both needle-directed (n = 34 cysts) and catheter-directed (n = 34 cysts) sclerotherapy techniques were effective, with a 100% technical success rate and a 97% clinical success rate. In two of 34 cysts (6%) treated with needle-directed sclerotherapy, recurrence was detected and successfully retreated with catheter-directed sclerotherapy. Significant reductions in cyst size, pain, and serum cancer antigen 125 levels (p < 0.05) were noted. Serum anti-Müllerian hormone levels remained unaffected, indicating preserved ovarian reserve (p > 0.05). Among those treated for infertility, the pregnancy rate was 54% (n = 6/11). The mean ± SD cyst size decline was greater in catheter-directed sclerotherapy than needle-directed sclerotherapy (5.5 ± 3.1 cm vs. 4.0 ± 2.1 cm, p < 0.05). However, the pretreatment cyst volumes were considerably higher in catheter-directed sclerotherapy group (202.0 ± 233.5 mL vs. 78.8 ± 59.7 mL, p < 0.05) and were associated with significant post-treatment volume decrease (p < 0.05)., Conclusion: The choice between catheter-directed and needle-directed ethanol sclerotherapy should be determined during the procedure, with a preference for catheter-directed sclerotherapy when feasible. Crucial factors in making this decision include cyst size, cyst location, cyst viscosity, and tissue rigidity. Level of evidence Level 3, non-controlled retrospective cohort study., (© 2024. The Author(s).)

Background: The serum P concentrations are suggested to have an impact on pregnancy outcome. However there is no consensus about the optimal progesterone cut-off during the luteal phase. Few studies evaluated the effectiveness of a "rescue protocol" for low serum P concentrations and most of these studies used vaginal progesterone administration. There is paucity of data on the effectiveness of rescue protocol using intramuscular progesterone (IM-P) in frozen-thawed embryo transfer (FET)., Methods: This study is a retrospective cohort study included 637 single or double blastocyst FETs with artificially prepared endometrium receiving 100 mg IM progesterone (P) after incremental estrogen treatment. Serum P concentrations were evaluated using blood samples obtained 117-119 hours after the first IM-P administration and 21 ± 2 hours after the last IM-P administration. Patients with serum P concentrations <20.6 ng/ml on the ET day were administrated 400 mg vaginal progesterone for rescue., Results: Demographic and cycle characteristics were similar between patients receiving rescue vaginal P (embryo transfer (ET)-day P concentration < 20.6 ng/ml) and patients who did not need rescue vaginal P (ET-day P concentration ≥ 20.6 ng/ml). Clinical pregnancy, miscarriage, and live birth rates were similar between two groups: 52.9%(45/85) vs 59.6%(326/552), p=0.287; 11.1%(5/45) vs 14.1%(46/326), p=0.583; and 47.1%(40/85) vs 50.7%(280/552), p=0.526, respectively. Logistic regression analysis revealed that the female age (p = 0.008, OR=0.942, 95% CI = 0.902-0.984) and embryo quality (ref: good quality for moderate: p=0.02, OR=0.469, 95% CI =0.269-0.760; for poor: p=0.013, OR= 0.269, 95% CI = 0.092-0.757) were independent variables for live birth. Following rescue protocol implementation, ET-day P concentration was not a significant predictor of live birth., Conclusions: Rescue vaginal P administration for low ET day serum P concentrations following IM-P yields comparable live birth rates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Boynukalin, Tohma, Yarkıner, Gultomruk, Bozdag, Ozkavukcu, Bahçeci and Demir.)

Purpose: Patients with polycystic ovarian morphology (PCOM) make up 20% cases for assisted reproductive technology (ART). Folliculogenesis is impaired in PCOS. Signaling molecules are involved in follicle development. Dysregulations of intrafollicular environment and signaling molecules are observed in PCOS. Granulosa cells (GCs) and oocytes secrete molecules into follicular fluid by exocytosis of SNAREs. The aim of this study is to evaluate vesicle transport and vesicle fusion proteins (SNAREs) in GCs from PCOS patients who have undergone IVF treatment., Methods: Follicular fluids were collected from patients who undergo IVF/ICSI with the diagnosis of male factor (n = 10) and PCOS (n = 10) patients. GCs were separated and cultured. Each group of GCs was stimulated with FSH-hCG. The cells were examined under electron microscope. Immunofluorescent labeling was performed on cells for Stx6, SNAP25, StxBP1, FSHr, and KITL. Integrated density was analyzed from images of Stx6, SNAP25, StxBP1, FSHr, and KITL., Results: Intercellular communication occurs by signal molecules; Stx6, SNAP25, and StxBP1 fusion proteins involved in exocytosis were decreased in the GCs of PCOS. There was no increase in in vitro stimulation with FSH-hCG either. In the electron microscope, it was observed that exocytosis of the vesicles was disrupted., Conclusions: Exocytosis and vesicular dynamics are among the basic physiological functions of human steroidogenic granulosa cells. Follicle development is necessary for production of competent oocytes and ovulation. Understanding the pathophysiology of PCOS at follicular level is important for disease management. According to our findings, deficits in vesicular dynamics of human granulosa cells in may be central to the treatment strategy for PCOS patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Study Question: Which add-ons are safe and effective to be used in ART treatment?, Summary Answer: Forty-two recommendations were formulated on the use of add-ons in the diagnosis of fertility problems, the IVF laboratory and clinical management of IVF treatment., What Is Known Already: The innovative nature of ART combined with the extremely high motivation of the patients has opened the door to the wide application of what has become known as 'add-ons' in reproductive medicine. These supplementary options are available to patients in addition to standard fertility procedures, typically incurring an additional cost. A diverse array of supplementary options is made available, encompassing tests, drugs, equipment, complementary or alternative therapies, laboratory procedures, and surgical interventions. These options share the common aim of stating to enhance pregnancy or live birth rates, mitigate the risk of miscarriage, or expedite the time to achieving pregnancy., Study Design, Size, Duration: ESHRE aimed to develop clinically relevant and evidence-based recommendations focusing on the safety and efficacy of add-ons currently used in fertility procedures in order to improve the quality of care for patients with infertility., Participants/materials, Setting, Methods: ESHRE appointed a European multidisciplinary working group consisting of practising clinicians, embryologists, and researchers who have demonstrated leadership and expertise in the care and research of infertility. Patient representatives were included in the working group. To ensure that the guidelines are evidence-based, the literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, recommendations were based on the professional experience and consensus of the working group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 46 independent international reviewers. A total of 272 comments were received and incorporated where relevant., Main Results and the Role of Chance: The multidisciplinary working group formulated 42 recommendations in three sections; diagnosis and diagnostic tests, laboratory tests and interventions, and clinical management., Limitations, Reasons for Caution: Of the 42 recommendations, none could be based on high-quality evidence and only four could be based on moderate-quality evidence, implicating that 95% of the recommendations are supported only by low-quality randomized controlled trials, observational data, professional experience, or consensus of the development group., Wider Implications of the Findings: These guidelines offer valuable direction for healthcare professionals who are responsible for the care of patients undergoing ART treatment for infertility. Their purpose is to promote safe and effective ART treatment, enabling patients to make informed decisions based on realistic expectations. The guidelines aim to ensure that patients are fully informed about the various treatment options available to them and the likelihood of any additional treatment or test to improve the chance of achieving a live birth., Study Funding/competing Interest(s): All costs relating to the development process were covered from ESHRE funds. There was no external funding of the development process or manuscript production. K.L. reports speakers fees from Merck and was part of a research study by Vitrolife (unpaid). T.E. reports consulting fees from Gynemed, speakers fees from Gynemed and is part of the scientific advisory board of Hamilton Thorne. N.P.P. reports grants from Merck Serono, Ferring Pharmaceutical, Theramex, Gedeon Richter, Organon, Roche, IBSA and Besins Healthcare, speakers fees from Merck Serono, Ferring Pharmaceutical, Theramex, Gedeon Richter, Organon, Roche, IBSA and Besins Healthcare. S.R.H. declares being managing director of Fertility Europe, a not-for-profit organization receiving financial support from ESHRE. I.S. is a scientific advisor for and has stock options from Alife Health, is co-founder of IVFvision LTD (unpaid) and received speakers' fee from the 2023 ART Young Leader Prestige workshop in China. A.P. reports grants from Gedeon Richter, Ferring Pharmaceuticals and Merck A/S, consulting fees from Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos and Merck A/S, speakers fees from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, Theramex and Organon, travel fees from Gedeon Richter. The other authors disclosed no conflicts of interest., Disclaimer: This Good Practice Recommendations (GPRs) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and are based on the scientific evidence available at the time of preparation.ESHRE GPRs should be used for information and educational purposes. They should not be interpreted as setting a standard of care or bedeemedinclusive of all proper methods of care, or be exclusive of other methods of care reasonably directed to obtaining the same results.Theydo not replace the need for application of clinical judgement to each individual presentation, or variations based on locality and facility type.Furthermore, ESHRE GPRs do not constitute or imply the endorsement, or favouring, of any of the included technologies by ESHRE., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Purpose: Endometrial compaction (EC) is defined as the difference in endometrial thickness from the end of the follicular phase to the day of embryo transfer (ET). We aimed to determine the role of EC in predicting assisted reproductive technology (ART) success by conducting a meta-analysis of studies reporting the association between EC and clinical outcomes of ART., Methods: MEDLINE via PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from the date of inception to May 19, 2023. The primary outcome was live birth rate (LBR) per ET. Secondary outcomes were live birth or ongoing pregnancy per ET, ongoing pregnancy per ET, clinical pregnancy per ET, and miscarriage per clinical pregnancy., Results: Fifteen studies were included. When data from all studies reporting live birth were pooled, overall LBR rates were comparable in cycles showing EC or not [RR = 0.97, 95%CI = 0.92 to 1.02; 10 studies, 11,710 transfer cycles]. In a subgroup of studies that included euploid ET cycles, a similar LBR for patients with and without EC was noted [RR = 0.99, 95%CI = 0.86 to 1.13, 4 studies, 1172 cycles]. The miscarriage rate did not seem to be affected by the presence or absence of EC [RR = 1.06, 95%CI = 0.90 to 1.24; 12 studies]., Conclusion: The predictive value of EC in determining LBR is limited, and assessment of EC may no longer be necessary, given these findings., Trial Registration: PROSPERO CRD42023410389., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Granulosa cells are the cell population who have an increasing importance in the female genital system and reproduction. Thus, nowadays in vitro studies to address these cells are also gaining importance and attracts researcher's attention. The aim of our study is to develop a more feasible, low-cost granulosa cell isolation and culture method compared to methods defined so far. Granulosa cells were isolated from follicular fluids obtained from both healthy women donors (n = 19) and polycystic ovary syndrome (n = 15) applied to in vitro fertilization treatment process. Granulosa cells were isolated by using Lymphosep® separation fluid that was not used for this purpose before. The isolated cells were cultured in suitable culture dishes with a mixture of BIO-AMFTM-1 and DMEM/F12 in the first seeding and only complete DMEM/F12 in the following feeds. Complete medium contains only 5% fetal calf serum, 4% L-glutamine and 1% penicillin-streptomycin-amphotericin. The new methods we have developed in granulosa cell isolation and in vitro culture have been successful. Reduction in supplement types and amount; improved the proliferation rate of the granulosa cells in culture. Our new methods of isolation and cell culture for granulosa cells from healthy women, have been also successful in samples of polycystic ovarian patients. With these developed methods, granulosa cells, which belong to humans and have an important role in the ovary, could be isolated and subsequently be maintained to reproduce (proliferate) more easily and cheaper., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Study Objective: This study aimed to evaluate the presence of anovulation in adolescents with primary dysmenorrhea (PD)., Design: Prospective cohort study., Setting: Hacettepe University Children's Hospital, Adolescent Medicine outpatient clinic between September 2018 and September 2019., Participants: Healthy female adolescents (between 11 and 18 years of age), with regular menstruation with a score of 1-3 according to the Numerical Rating Scale (NRS) and grade 0 (no limitation for daily activities, no analgesic need and systemic symptoms) according to the Verbal Multidimensional Scoring System (VBSS) were recruited as a control group. The participants who met the diagnostic criteria for PD with an NRS score ≥4, had analgesic need in at least the last 3 menstrual cycles, had defined moderate-to-severe PD according to VMSS (Grade 2-3), and had analgesic need every time were accepted as the PD group., Intervention and Main Outcome Measures: For the determination of ovulation, suprapubic pelvic ultrasound and luteal SP levels were used. The first day of menstruation (DOM) was accepted as the first day of the menstrual cycle. The participants were called to the outpatient clinic for a total of 3 visits during 1 cycle; the first visit was for the suprapubic pelvic ultrasound imaging on the 12 th -18 th DOM, the second visit was for the first SP level measurement on the 21 st -24 th DOM, and the third visit was for the second SP level measurement on the 28 th -31 st DOM, if the next expected menstruation has not started yet. Participants' anthropometric measurements, menstrual history, family history of dysmenorrhea, and additional symptoms accompanying pain were recorded., Results: Anovulatory cycle rates according to 2 different references for SP threshold values (3 and 5 ng/mL) were 31.7% and 36.6% in the PD group, and 44.4% and 55.6% in the control group, respectively (P = .250, P = .095). In the PD group, NRS scores were similar for the ovulatory and anovulatory cycles for both SP threshold values (P = .320, P = .205). When the reference value for SP threshold was accepted as ≥5 ng/mL, the NRS score was significantly higher in the ovulatory group (P = .0017). When the distribution percentages of SP levels were evaluated among all participants, the median value was 5.5 ng/mL., Conclusion: Contrary to classical information, anovulatory cycles are not rare in PD patients, and pain severity is at the same level in these cycles. The pathogenesis of PD in adolescents requires further study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Despite the worldwide increase in frozen embryo transfer, the search for the best protocol to prime endometrium continues. Well-designed trials comparing various frozen embryo transfer protocols in terms of live birth rates, maternal, obstetric and neonatal outcome are urgently required. Currently, low-quality evidence indicates that, natural cycle, either true natural cycle or modified natural cycle, is superior to hormone replacement treatment protocol. Regarding warmed blastocyst transfer and frozen embryo transfer timing, the evidence suggests the 6 th day of progesterone start, LH surge+6 day and hCG+7 day in hormone replacement treatment, true natural cycle and modified natural cycle protocols, respectively. Time corrections, due to inter-personal differences in the window of implantation or day of vitrification (day 5 or 6), should be explored further. Recently available evidence clearly indicates that, in hormone replacement treatment and natural cycles, there might be marked inter-personal variation in serum progesterone levels with an impact on reproductive outcomes, despite the use of the same dose and route of progesterone administration. The place of progesterone rescue protocols in patients with low serum progesterone levels one day prior to warmed blastocyst transfer in hormone replacement treatment and natural cycles is likely to be intensively explored in near future., Competing Interests: HY, EP, and GB declare receipt of honorarium for lectures from Merck and research grants from Merck and Ferring. SE declares receipt of unrestricted research grants from Merck and lecture fees from Merck and Med.E.A. PH has received unrestricted research grants from MSD and Merck, as well as honoraria for lectures from MSD, Merck, Gedeon–Richter, Theramex, and IBSA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mumusoglu, Polat, Ozbek, Bozdag, Papanikolaou, Esteves, Humaidan and Yarali.)

Research Question: Will luteal phase rescue with additional progesterone increase serum progesterone concentrations and improve reproductive outcomes in patients with low serum progesterone concentrations undergoing hormone replacement therapy (HRT) cycles?, Design: Case-control study including 40 consecutive patients with serum progesterone concentrations <8.75 ng/ml on the 5th day of progesterone supplementation who underwent rescue with a daily bolus of 25 mg s.c. progesterone, starting on the afternoon of the 5th day of progesterone administration. For every patient who underwent progesterone rescue, three patients matched by age, body mass index, number of previous attempts and number of blastocysts transferred, with serum progesterone concentration >8.75 ng/ml on the 5th day of progesterone administration served as controls (n = 120). The main outcome measure was ongoing pregnancy rate (OPR)., Results: Baseline demographic features and embryological data of the rescue and control groups were comparable. As expected, the mean serum progesterone concentration was lower in the rescue group on the 5th day of progesterone administration (7.84 ± 0.92 versus 15.32 ± 5.02 ng/ml; P < 0.001). Following rescue, the mean serum progesterone concentration on the day of vitrified-warmed embryo transfer (6th day of progesterone administration) was 33.43 ± 10.83 ng/ml (range 14.61-82.64 ng/ml), and the OPR of the rescue and control groups were comparable., Conclusions: In patients undergoing HRT vitrified-warmed blastocyst transfer with serum progesterone concentrations lower than 8.75 ng/ml 1 day prior to the scheduled embryo transfer (6th day of progesterone administration), additional supplementation with a 25 mg s.c. daily progesterone dose seems to rescue the cycle, resulting in OPR comparable to those of patients with serum progesterone >8.75 ng/ml., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Recent advances in our recognition of two to three follicular waves of development in a single menstrual cycle has challenged the dogmatic approach of ovarian stimulation for in vitro fertilization starting in the early follicular phase. First shown in veterinary medicine and thereafter in women, luteal phase stimulation-derived oocytes are at least as competent as those retrieved following follicular phase stimulation. Poor ovarian responders still remain a challenge for many decades simply because they do not respond to ovarian stimulation. Performing follicular phase stimulation and luteal phase stimulation in the same menstrual cycle, named as double stimulation/dual stimulation, clearly increases the number of oocytes, which is a robust surrogate marker of live birth rate in in vitro fertilization across all female ages. Of interest, apart from one study, the bulk of evidence reports significantly higher number of oocytes following luteal phase stimulation when compared with follicular phase stimulation; hence, performing double stimulation/dual stimulation doubles the number of oocytes leading to a marked decrease in patient drop-out rate which is one of the major factors limiting cumulative live birth rates in such poor prognosis patients. The limited data with double stimulation/dual stimulation-derived embryos is reassuring for obstetric and neonatal outcome. The mandatory requirement of freeze-all and lack of cost-effectiveness data are limitations of this novel approach. Double stimulation/dual stimulation is an effective strategy when the need to obtain oocytes is urgent, including patients with malignant diseases undergoing oocyte cryopreservation and patients of advanced maternal age or with reduced ovarian reserve., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Research Question: To assess incidence of abnormal cleavage among biopsied blastocysts; to compare euploidy rates of the blastocysts with abnormal and normal cleavage; and to compare single euploid blastocyst transfer (SEBT) outcome derived from embryos with normal or abnormal cleavage., Design: Retrospective analysis of prospectively collected data in a private IVF clinic. Consecutive 554 patients (749 cycles) undergoing preimplantation genetic testing for aneuploidy (n = 497; 671 cycles) or monogenic diseases (n = 57; 78 cycles) were included. All assessments for abnormal cleavage were carried out retrospectively; presence of abnormal cleavage was not a factor in deciding which euploid embryo to transfer. A total of 1015 blastocysts were biopsied and 295 SEBT procedures were carried out. Main outcome measure was live birth rate (LBR)., Results: Incidence of reverse cleavage, direct cleavage, and reverse plus direct cleavage, were 7.7%, 6.4% and 2.3%, respectively. Of the 1015 biopsied blastocysts, 35.0% were euploid. Blastocysts with abnormal cleavage, in total, had a significantly higher euploidy rate compared with blastocysts with normal cleavage (44.6% [74/166] versus 33.1% [281/849]; P = 0.017). The LBR after SEBT with normal, reverse and direct cleavage, and direct cleavage plus reverse cleavage, was 133/238 (55.9%), 6/26 (23.1%), 8/24 (33.3%) and 0/3 (0.0%) (P < 0.001). Generalized estimating equation analysis showed that the presence of abnormal cleavage pattern was the only independent predictor of LBR (OR 0.316; 95% CI 0.115 to 0.867; P = 0.013)., Conclusions: Blastocysts with direct or reverse cleavage should be biopsied in preimplantation genetic testing cycles if they are morphologically eligible. Euploid blastocysts with abnormal cleavage, however, have approximately half the LBR of those euploid blastocyst with normal cleavage, hence, blastocysts with abnormal cleavage should have lower priority for transfer., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does intramuscular progesterone supplementation ensure ongoing pregnancy rates (OPR) comparable with vaginal progesterone only in hormone replacement therapy cycles for vitrified-warmed embryo transfer; and is there a window of serum progesterone concentration out of which reproductive outcomes may be negatively affected?, Design: Retrospective longitudinal cohort study carried out at a single IVF clinic. In total, 475 consecutive, day-5 to day-6 vitrified-warmed embryo transfer cycles using hormone replacement therapy regimen were included. Vaginal progesterone only was given to 143 patients; supplementation of vaginal progesterone only with intramuscular progesterone supplementation every third day was given to 332 patients. On the sixth day of progesterone administration, immediately before frozen-thawed embryo transfer, circulating progesterone levels were measured. Main outcome measure was OPR., Results: The baseline demographic features and embryological data of the vaginal progesterone only and intramuscular progesterone supplementation groups were comparable. The OPR were 48.3% and 51.8%, respectively (P = 0.477). Neither the circulating progesterone level nor the type of progesterone administration were independent predictors of OPR. The effect of serum progesterone levels on OPR was evaluated by percentiles (<10%, 10-49%, 50-90% and >90%), taking 50-90% as the reference sub-group. All percentiles in the intramuscular progesterone supplementation group and in the vaginal progesterone only group had similar OPR., Conclusions: Intramuscular progesterone supplementation every third day, overall, does not enhance OPR compared with vaginal progesterone only., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

This multicenter study evaluated the reliability of the recently published ART calculator for predicting the minimum number of metaphase II (MII) oocytes (MIImin) to obtain at least one euploid blastocyst in patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). We used clinical and embryonic retrospective data of 1,464 consecutive infertile couples who underwent IVF/ICSI with the intention to have preimplantation genetic testing for aneuploidy. The validation procedure followed a stepwise approach. Firstly, we assessed the distribution of euploid blastocysts per patient and found that it followed a negative binomial distribution. Secondly, we used generalized linear models and applied the Lasso procedure-including MII oocytes to adjust the data-to select the factors predicting the response variable "euploid blastocyst." Third, a logistic regression model-fit to the binomial response euploid (yes/no) for each MII oocyte-was built using the relevant factors. The observational unit was the "woman" whereas the response was the pair (m, n), where n is the number of retrieved MII oocytes and m the corresponding number of euploid blastocysts. The model was internally validated by randomly splitting the data into training and validation sets. The R-squares (~0.25) and the area under the ROC curve (~0.70) did not differ between the training and validation datasets. Fourth, mathematical equations and the calculated probabilities generated by the validation model were used to determine the MIImin required for obtaining at least one euploid blastocyst according to different success probabilities. Lastly, we compared the fittings generated by the validation model and the ART calculator and assessed the predictive value of the latter using the validation dataset. The fittings were sufficiently close for both the estimated probabilities of blastocyst euploid per MII oocyte ( r = 0.91) and MIImin ( r = 0.88). The ART calculator positive predictive values, i.e., the frequency of patients with at least one euploid blastocyst among those who achieved the estimated MIImin, were 84.8%, 87.5%, and 90.0% for 70%, 80%, and 90% predicted probabilities of success, respectively. The ART calculator effectively predicts the MIImin needed to achieve at least one euploid blastocyst in individual patients undergoing IVF/ICSI. The prediction tool might be used for counseling and planning IVF/ICSI treatments., (Copyright © 2020 Esteves, Yarali, Ubaldi, Carvalho, Bento, Vaiarelli, Cimadomo, Özbek, Polat, Bozdag, Rienzi and Alviggi.)

Despite the wide utilization of gonadotropin-releasing hormone analogs, progesterone elevation (P 4 E) in the late follicular phase occurs in 5 to 30% of all ovarian stimulation (OS) cycles. Although the detrimental effect of P 4 E on pregnancy rates in fresh in vitro fertilization cycles is valid in all subsets of cases, higher levels of P 4 and a longer duration of P 4 E may be needed in patients with a hyper-ovarian response in order for a negative impact on pregnancy rates to occur. Available preclinical and clinical data suggest that aggressive OS with high doses of follicle-stimulating hormone might increase 3β-hydroxy steroid dehydrogenase and 17β-hydroxy steroid dehydrogenase enzyme activity in human granulosa cells, which leads to high P 4 production and hence a higher amount of leakage to the systemic circulation due to a lack of 17α-hydroxylase enzyme expression in human species. High P 4 concentrations appear to alter gene expression in the endometrium; however, caution is necessary regarding its potential effect on oocyte/embryo quality with respect to the role of inherent follicular disruption in some women. In terms of the mechanism of overproduction in P 4 synthesis, the main preventive strategy should be avoiding aggressive stimulation. Unfortunately, there is lack of large-scale randomized controlled trials for other approaches, including deferred embryo transfer in the thaw cycle. Since there is a significant inter-assay variability for P 4 measurement, it may be wise to recommend that every center should define their own P 4 E and the level needed for harm to occur based on their own assays and datasets before deciding the best approach., Competing Interests: The authors declare that they have no conflict of interest., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Research Question: Is anti-Müllerian hormone (AMH) a valid tool to diagnose polycystic ovary syndrome (PCOS) according to different subsets of criteria among an unselected group of women?, Design: In this cross-sectional study, AMH concentrations were measured in an unselected group of women. The ability of AMH to diagnose PCOS according to National Institutes of Health (NIH), Rotterdam-2003 and Androgen Excess and PCOS Society (AE-PCOS) criteria was tested by using frozen serum aliquots (n = 392) that had been collected from a previous prevalence study of PCOS., Results: The respective age and body mass index adjusted area under the curve (aAUC, 95% confidence interval) values were 0.80 (0.71-0.89), 0.74 (0.67-0.81) and 0.71 (0.64-0.79). When the definition of polycystic ovary morphology (PCOM) was set to an antral follicle count (AFC) of 20 instead of 12, the prevalence of syndrome dropped from 19.9% to 10.2% and from 15.3% to 8.9% according to Rotterdam-2003 and AE-PCOS criteria, respectively. In patients with Phenotype A, who had hyperandrogenism, ovulatory dysfunction and PCOM, AMH had an aAUC of 0.85 (0.77-0.92) to diagnose the syndrome. In Phenotypes B (hyperandrogenism + ovulatory dysfunction), C (hyperandrogenism + PCOM) or D (ovulatory dysfunction + PCOM), AMH had poor to fair ability to diagnose the syndrome., Conclusion: AMH has poor to fair validity to diagnose PCOS among an unselected group of women, except for patients bearing all features of the syndrome (Phenotype A). This finding is valid using the NIH, Rotterdam-2003 and AE-PCOS criteria and even after revising the definition of PCOM as AFC ≥20., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does preimplantation genetic testing for aneuploidy (PGT-A) influence the discontinuation rate in women with advanced maternal age (AMA) undergoing IVF?, Design: Retrospective longitudinal cohort study carried out at a single IVF clinic in Turkey. In total, 401 consecutive AMA cases were included. Discontinuation rates of pre-intervention (conventional IVF; June 2013 to October 2014; 203 couples; 270 cycles) and post-intervention (PGT-A; April 2015 to June 2016; 198 couples; 285 cycles) periods were compared. To delineate the reason for discontinuation, a telephone survey was conducted. Primary outcome measure was cumulative discontinuation rate before completing three cycles of IVF treatment without achieving an ongoing pregnancy., Results: The discontinuation rates after the first and second failed cycles were comparable between the two arms as were the cumulative discontinuation rates before completing three cycles. The cumulative ongoing pregnancy rate per embryo transfer was significantly higher in the PGT-A arm (43.2% versus 16.8%; P < 0.001). The cumulative ongoing pregnancy rate per patient was comparable between the two arms (20.7% versus 16.3%, respectively). Female age was the only significant contributor to treatment discontinuation (hazard ratio [HR] 1.07; 95% CI 1.09 to 1.13). Of the 296 couples discontinuing treatment in both arms, 179 (179/296 [60.5%]) participated in the survey; overall, psychological burden was the main reason for treatment discontinuation (37/179 [20.7%])., Conclusions: About 90% of AMA cases not achieving an ongoing pregnancy discontinue IVF treatment before completing three cycles. Discontinuation rate is not reduced by carrying out PGT-A. Female ageing is the only significant contributor, with a hazard of discontinuing further IVF treatment of 7% with female ageing of 1-year., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Adnexal torsion constitutes 2.7% of all gynecological emergencies. Because normal follicular growth has been demonstrated after examination of surgical specimens retrieved from oophorectomies, organ-sparing strategy has gained more popularity irrespective of the appearance of the ovary. However, the functionality of the remaining follicles has not been known. The aim of the study was to evaluate the effect of ischemia-reperfusion on fecundability in a rat model with adnexal torsion., Methods: A total of 30 female adult Wistar albino rats were assessed. In the first laparotomy, right ovaries were twisted for 8 (Group I, n = 10) or 24 (Group II, n = 10) hours. Second laparotomy was performed to untwist the torsion side and oophorectomy to the other side. In the control group (Group III, n = 10), left ovaries were removed and right ovaries were kept without any intervention. After 30 days from the last operation, female rats were mated for 10 days and euthanized 4 days later. Fecundability was calculated using beta-human chorionic gonadotropin (hCG) levels for detection of pregnancy rates., Results: The mean beta-hCG values in control, 8-hour, and 24-hour groups between pregnant rats were 19.8 ± 26.02, 11.7 ± 0.17, and 22.97 ± 11.87 mIU/mL, respectively. Whereas two out of 10 rats (20%) conceived in the 8-hour group, three out of 10 rats (30%) got pregnant in the 24-hour group. In total, whereas five out of the 20 rats got pregnant in the experimental groups, in the control group, seven out of 10 subjects conceived (25% vs 70 %, p = 0.018)., Conclusion: Although there was a statistical difference between experimental and control groups, statistical significance was not reached among 8-hour and 24-hour torsion subgroups. In this context, patients with torsion but treated with detorsion should be further investigated for their fecundability potency and be informed accordingly.

Purpose: There is no established non-invasive method to diagnose patients with endometriosis. As a nondestructive type of radiation, infrared light might be used for discrimination by causing vibration of the covalent bonds of the molecules when absorbed by the tissues. The aim of the study was to test whether cervical swab can be used to diagnose women with endometriosis using Fourier transform infrared spectroscopy (FTIR)., Methods: In this prospective case-control study, women between 18-45 years old and undergoing laparoscopy due to various reasons were recruited (n = 20). According to the findings during laparoscopy, patients were stratified as stage I-II or stage III-IV endometriosis groups. Women lacking any visible lesions of endometriosis were recruited as controls. A cervical swab was taken from all patients just before the surgical procedure and pulled into a tube containing saline solution. FTIR spectra were obtained and the fingerprint region (1750-850 cm -1 ) was used for analyses., Results: Finally, three samples in stage I-II, five samples in stage III-IV and five samples in the control group were analyzed. Hierarchical cluster analysis and principal component analysis were performed as the chemometric method. A total of ten observable peaks were detected in the absorbance spectra of samples. The peaks at 1450 and 1405 cm -1 originating from lipids and proteins significantly increased in the stage III-IV endometriosis group when compared with controls. In addition, nucleic acid/carbohydrate ratio was significantly lower in the stage I-II group indicating that the alteration of the carbohydrate level might be important., Conclusions: Examination of cervical swab with FTIR spectroscopy might be a proper candidate for a non-invasive diagnostic approach of endometriosis.