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To investigate whether endometrial thickness (ET) independently affects the live birth rate (LBR) after embryo transfer. Retrospective study. Private assisted reproductive technology center. A total of 959 single euploid frozen embryo transfers. Vitrified euploid blastocyst transfer. Live birth rate per embryo transfer. The conditional density plots did not demonstrate either a linear relationship between the ET and LBR or a threshold below which the LBR decreased perceivably. Receiver operating characteristic curve analyses did not suggest a predictive value of the ET for the LBR. The area under the curve values were 0.55, 0.54, and 0.54 in the overall, programmed, and natural cycle transfers, respectively. Logistic regression analyses with age, embryo quality, day of trophectoderm biopsy, body mass index, and ET did not suggest an independent effect of the ET on the LBR. We did not identify a threshold of the ET that either precluded live birth or under which the LBR decreases perceivably. Common practice of cancelling embryo transfers when the ET is <7 mm may not be justified. Prospective studies, in which the management of the transfer cycle would not be altered by ET, would provide higher-quality evidence on the subject. [ABSTRACT FROM AUTHOR]

Background: The key to optimal timing of frozen embryo transfer (FET) is to synchronize the embryo with the receptive phase of the endometrium. Secretory transformation of the endometrium is induced by progesterone. In contrast, detection of the luteinizing hormone (LH) surge is the most common surrogate used to determine the start of secretory transformation and to schedule FET in a natural cycle. The accuracy of LH monitoring to schedule FET in a natural cycle relies heavily on the assumption that the period between the LH surge and ovulation is acceptably constant. This study will determine the period between LH rise and progesterone rise in ovulatory natural menstrual cycles. Methods: Retrospective observational study including 102 women who underwent ultrasound and endocrine monitoring for a frozen embryo transfer in a natural cycle. All women had serum LH, estradiol and progesterone levels measured on three consecutive days until (including) the day of ovulation defined with serum progesterone level exceeding 1ng/ml. Results: Twenty-one (20.6%) women had the LH rise 2 days prior to progesterone rise, 71 (69.6%) had on the day immediately preceding progesterone rise and 10 (9.8%) on the same day of progesterone rise. Women who had LH rise 2 days prior to progesterone rise had significantly higher body mass index and significantly lower serum AMH levels than women who had LH rise on the same day with progesterone rise. Conclusion: This study provides an unbiased account of the temporal relationship between LH and progesterone increase in a natural menstrual cycle. Variation in the period between LH rise and progesterone rise in ovulatory cycles likely has implications for the choice of marker for the start of secretory transformation in frozen embryo transfer cycles. The study participants are representative of the relevant population of women undergoing frozen embryo transfer in a natural cycle. [ABSTRACT FROM AUTHOR]

Background: In 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain.Objective and Rationale: This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals.Search Methods: PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on 'SARS-CoV-2' and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible.Outcomes: From the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients' performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients.Wider Implications: This review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research. The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil. [ABSTRACT FROM AUTHOR]

Objective: To present a definition of recurrent implantation failure that accounts for the effects of female age and anticipated blastocyst euploidy rates on cumulative implantation rates.Design: Mathematical modeling.Setting: Not applicable.Patient(s): Not applicable.Intervention(s): Mathematical modeling of cumulative implantation probability on the basis of published blastocyst euploidy rates across categories of female age.Main Outcome Measure(s): The number of blastocysts required to achieve 95% cumulative implantation probability under the assumption of the absence of any other factor affecting implantation.Result(s): When the euploidy status of the transferred embryo is unknown (i.e., not subjected to preimplantation genetic testing for aneuploidies), our simulation shows that no age category reaches 95% cumulative probability of implantation of at least one embryo until after transfer of seven blastocysts. The number of blastocysts required to reach the same threshold is higher for older patients. For example, women older than 38 years require transfer of more than 10 untested blastocysts for the upper range of predictive probability to meet the threshold of 95%. On the other hand, if the implantation rate for a euploid blastocyst is assumed to be 55%, then 4 blastocysts are enough to reach a cumulative probability rate greater than 95%, regardless of age.Conclusion(s): The term "recurrent implantation failure" should be a functional term guiding further management. We suggest that recurrent implantation failure should not be called until implantation failure becomes reasonably likely to be caused by factors other than embryo aneuploidy, the leading cause of implantation failure. We propose a new definition that factors in anticipated blastocyst euploidy rates across categories of female age, euploid blastocyst implantation rate, and a specified threshold of cumulative probability of implantation. [ABSTRACT FROM AUTHOR]

Study Question: What is the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the outcome of a pregnancy after medically assisted reproduction (MAR)?Summary Answer: Our results suggest that MAR pregnancies are not differentially affected by SARS-CoV-2 infection compared to spontaneous pregnancies.What Is Known Already: Information on the effects of coronavirus disease 2019 (COVID-19) on pregnancy after MAR is scarce when women get infected during MAR or early pregnancy, even though such information is vital for informing women seeking pregnancy.Study Design, Size, Duration: Data from SARS-CoV-2 affected MAR pregnancies were collected between May 2020 and June 2021 through a voluntary data collection, organised by the European Society of Human Reproduction and Embryology (ESHRE).Participants/materials, Setting, Methods: All ESHRE members were invited to participate to an online data collection for SARS-CoV-2-infected MAR pregnancies.Main Results and the Role Of Chance: The dataset includes 80 cases from 32 countries, including 67 live births, 10 miscarriages, 2 stillbirths and 1 maternal death. An additional 25pregnancies were ongoing at the time of writing.Limitations, Reasons For Caution: An international data registry based on voluntary contribution can be subject to selective reporting with possible risks of over- or under-estimation.Wider Implications Of the Findings: The current data can be used to guide clinical decisions in the care of women pregnant after MAR, in the context of the COVID-19 pandemic.Study Funding/competing Interest(s): The authors acknowledge the support of ESHRE for the data registry and meetings. J.S.T. reports grants or contracts from Sigrid Juselius Foundation, EU and Helsinki University Hospital Funds, outside the scope of the current work. The other authors declare that they have no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

PGDIS Position statement on chromosome mosaicism and preimplantation aneuploidy testing at the blastocyst statement. Sir, [2] report live births from blastocysts with "abnormal" results, which were previously denied transfer. In the study by [2], after excluding results predicting "mosaicism" and "segmental aberrations", the transfer embryos with uniform whole chromosome aneuploidies, led to a clinical pregnancy loss rate of 100% (5/5 transfers with exclusively full chromosome aneuploid embryos). [Extracted from the article]

Sir, [2] report live births from blastocysts with "abnormal" results, which were previously denied transfer. PGDIS Position statement on chromosome mosaicism and preimplantation aneuploidy testing at the blastocyst statement. In the study by [2], after excluding results predicting "mosaicism" and "segmental aberrations", the transfer embryos with uniform whole chromosome aneuploidies, led to a clinical pregnancy loss rate of 100% (5/5 transfers with exclusively full chromosome aneuploid embryos). [Extracted from the article]

Background: Progestins are capable of suppressing endogenous LH secretion from the pituitary. Progestins can be used orally and are less expensive than GnRH analogues. However, early endometrial exposure to progestin precludes a fresh embryo transfer (ET), but the advent of vitrification and increasing number of oocyte cryopreservation cycles allow more opportunities for using progestins for pituitary suppression.Objective and Rationale: This review summarizes: the mechanism of pituitary suppression by progestins; the effectiveness of progestins when compared with GnRH analogues and with each other; the effect of progestins on oocyte and embryo developmental potential and euploidy status; and the cost-effectiveness aspects of progestin primed stimulation. Future research priorities are also identified.Search Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, the Web of Science and Scopus were screened with a combination of keywords related to ART, progesterone, GnRH analogue and ovarian stimulation, in various combinations. The search period was from the date of inception of each database until 1 April 2020. Only full text papers published in English were included.Outcomes: Overall, the duration of stimulation, gonadotrophin consumption and oocyte yield were similar with progestins and GnRH analogues. However, sensitivity analyses suggested that progestins were associated with significantly lower gonadotrophin consumption than the long GnRH agonist protocol (mean difference (MD) = -648, 95% CI = -746 to -550 IU) and significantly higher gonadotrophin consumption than the short GnRH agonist protocol (MD = 433, 95% CI = 311 to 555 IU). Overall, live birth, ongoing and clinical pregnancy rates per ET were similar with progestins and GnRH analogues. However, when progestins were compared with GnRH agonists, sensitivity analyses including women with polycystic ovary syndrome (risk ratio (RR) = 1.27, 95% CI = 1.06 to 1.53) and short GnRH agonist protocols (RR = 1.14, 95% CI = 1.02 to 1.28) showed significantly higher clinical pregnancy rates with progestins. However, the quality of evidence is low. Studies comparing medroxyprogesterone acetate, dydrogesterone and micronized progesterone suggested similar ovarian response and pregnancy outcomes. The euploidy status of embryos from progestin primed cycles was similar to that of embryos from conventional stimulation cycles. Available information is reassuring regarding obstetric and neonatal outcomes with the use of progestins. Despite the lower cost of progestins than GnRH analogues, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase cost per live birth with progestins as compared to an ART cycle culminating in a fresh ET.Wider Implications: Progestins can present an effective option for women who do not contemplate a fresh ET, e.g. fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, double stimulation cycles. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether endometrioma is associated with a progressive decline in ovarian reserve, and to compare the rate of decline with natural decline in ovarian reserve.Design: Prospective, observational study.Setting: Tertiary university hospital, endometriosis clinic.Patient(s): Forty women with endometrioma and 40 age-matched healthy controls.Intervention(s): Women with endometriomas who did not need hormonal/surgical treatment at the time of recruitment and were expectantly managed. Controls were age-matched, healthy women. All participants underwent serum antimüllerian hormone (AMH) testing twice, 6 months apart. Sexually active patients with endometrioma also underwent antral follicle count.Main Outcome Measure(s): Change in serum AMH levels.Result(s): Median (25th-75th percentile) serum AMH level at recruitment was 2.83 (0.70-4.96) ng/mL in the endometrioma group and 4.42 (2.26-5.57) ng/mL in the control group. The median percent decline in serum AMH level was 26.4% (11.36%-55.41%) in the endometrioma group and 7.4% (-11.98%, 29.33%) in the control groups. Twenty-two women with endometrioma who had antral follicle count (AFC) had median AFC of 10 (8-12) at recruitment and 8 (6.3-10) at 6 months.Conclusion(s): Women with endometrioma experience a progressive decline in serum AMH levels, which is faster than that in healthy women.Clinical Trial Registration Number: NCT02438735. [ABSTRACT FROM AUTHOR]

Study Question: Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma?Summary Answer: Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma.What Is Already Known: Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas.Study Design, Size, Duration: A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period.Participants/materials, Setting, Methods: Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded.Main Results and the Role Of Chance: Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3).Limitations, Reasons For Caution: The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment.Wider Implications Of the Findings: The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified.Study Funding/competing Interest(s): No funding or competing interests to declare.Trial Registration Number: None. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to provide an overview of the studies investigating a possible association between thrombophilia and assisted reproductive technology (ART) outcome. Methods: This is a literature review. Results: Congenital thrombophilias (CoT) are reported to be associated with pregnancy loss. However, the association between CoT and early pregnancy loss is weak and does not necessarily support causation. CoT are more likely to be associated with late fetal loss. Even though data pooled from case-control and cohort studies suggest an increased risk of ART failure in women with CoTs, there seems no association when the analysis is confined to better quality cohort studies. The evidence supporting anticoagulation to improve ART outcome in CoT carriers is weak. Likewise, studies on antiphospholipid antibodies (APAs) and ART outcome suffer from multiple methodological limitations and a detrimental impact of APA positivity is controversial. Empirical administration of heparin or low molecular weight heparin to women with recurrent ART failures is supported by weak evidence. Importantly, thrombophilias are likely to increase thrombotic complications after ovarian stimulation for ART. Conclusions: Current evidence does not support routinely testing for or treatment of thrombophilia in the setting of ART nor in couples with implantation failure. A careful personal and family history should be obtained and a risk assessment for thrombotic complications should be made in every woman undergoing ovarian stimulation. If positive, testing for thrombophilia is warranted. [ABSTRACT FROM AUTHOR]

Objective: To compare complication rates and pain scores after oocyte pickup (OPU) in in vitro maturation (IVM) and IVF cycles. Design: Retrospective cohort study. Setting: University-affiliated ART center. Patient(s): One hundred eighty-eight IVM and 188 IVF OPUs. Intervention(s): IVM OPUs were done using a 19-gauge single-lumen needle, and IVF OPUs were done using a 17-gauge single- or 16-gauge double-lumen needles. Main Outcome Measure(s): Duration of OPU, complication rates, and pain scores during the OPU procedure. Result(s): IVM OPU took significantly more time than IVF OPU (22 vs. 15 minutes). Two women in the IVM and four in the IVF group experienced bleeding from the vaginal wall or ovary. None of them required hospitalization, transfusion, or an operative intervention. One patient in each group had pelvic infection. Severe post-OPU abdominal pain occurred in one patient in the IVM group and five patients in the IVF group. No differences were found between pain scores in the IVF and IVM groups (3.4 vs. 3.8). Conclusion(s): Although IVM OPU requires more punctures per ovary, it is well tolerated and does not seem to be associated with a higher complication rate than IVF OPU. [ABSTRACT FROM AUTHOR]

Objective: To compare complication rates and pain scores after oocyte pickup (OPU) in in vitro maturation (IVM) and IVF cycles. Design: Retrospective cohort study. Setting: University-affiliated ART center. Patient(s): One hundred eighty-eight IVM and 188 IVF OPUs. Intervention(s): IVM OPUs were done using a 19-gauge single-lumen needle, and IVF OPUs were done using a 17-gauge single- or 16-gauge double-lumen needles. Main Outcome Measure(s): Duration of OPU, complication rates, and pain scores during the OPU procedure. Result(s): IVM OPU took significantly more time than IVF OPU (22 vs. 15 minutes). Two women in the IVM and four in the IVF group experienced bleeding from the vaginal wall or ovary. None of them required hospitalization, transfusion, or an operative intervention. One patient in each group had pelvic infection. Severe post-OPU abdominal pain occurred in one patient in the IVM group and five patients in the IVF group. No differences were found between pain scores in the IVF and IVM groups (3.4 vs. 3.8). Conclusion(s): Although IVM OPU requires more punctures per ovary, it is well tolerated and does not seem to be associated with a higher complication rate than IVF OPU. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is severe early ovarian hyperstimulation syndrome (OHSS) completely prevented with the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol? SUMMARY ANSWER Severe early OHSS can occur even after the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol. WHAT IS KNOWN ALREADY Prior studies including over 200 women who received the GnRH agonist trigger and 1500 hCG luteal rescue protocol have reported complete prevention of severe early OHSS. Only a few late OHSS cases have been reported and it has been suggested that this protocol can be safely applied to any women under risk. STUDY DESIGN, SIZE, DURATION This retrospective cohort study included all women who were at high risk of OHSS and were given the GnRH agonist trigger plus hCG luteal rescue protocol between December 2008 and August 2012 in the two participating centers. PARTICIPANTS/MATERIALS, SETTING, METHODS There were 23 women with a mean estradiol level of 4891 ± 2214 pg/ml and a mean number of >12 mm follicles of 20 ± 6 on the day of ovulation triggering. OHSS was categorized according to the Golan criteria. MAIN RESULTS AND THE ROLE OF CHANCE Overall 6 of the 23 (26%) women developed severe OHSS. Five women had severe early OHSS requiring ascites drainage and hospitalization and three of these women did not undergo embryo transfer. The number of follicles measuring 10–14 mm on the day of triggering was significantly different between women who developed severe early OHSS and those who did not. LIMITATIONS, REASONS FOR CAUTION The small number of women with severe early OHSS may have prevented identification of other significant risk factors. WIDER IMPLICATIONS OF THE FINDINGS Although the GnRH agonist plus 1500 IU hCG luteal rescue protocol significantly decreases the risk of severe OHSS, this life threatening complication can still occur in high-risk patients. It would be prudent to avoid hCG luteal rescue and freeze all embryos for future transfer in such women particularly when there are ≥18 follicles with 10–14 mm diameters even with few larger follicles. STUDY FUNDING/COMPETING INTEREST(S) No funding was sought for this report. The authors have no conflict of interest to declare. [ABSTRACT FROM PUBLISHER]

Objective: To review studies assessing the application of ultrasound automated volume calculation in reproductive medicine. Design: We performed a literature search using the keywords "SonoAVC, sonography-based automated volume calculation, automated ultrasound, 3D ultrasound, antral follicle, follicle volume, follicle monitoring, follicle tracking, in vitro fertilization, controlled ovarian hyperstimulation, embryo volume, embryonic volume, gestational sac, and fetal volume" and conducted the search in PubMed, Medline, EMBASE, and the Cochrane Database of Systematic Reviews. Reference lists of identified reports were manually searched for other relevant publications. Result(s): Automated volume measurements are in very good agreement with actual volumes of the assessed structures or with other validated measurement methods. The technique seems to provide reliable and highly reproducible results under a variety of conditions. Automated measurements take less time than manual measurements. Conclusion(s): Ultrasound automated volume calculation is a promising new technology which is already used in daily practice especially for assisted reproduction. Improvements to the technology will undoubtedly render it more effective and increase its use. [ABSTRACT FROM AUTHOR]

Background: Ovarian response to gonadotrophin stimulation is monitored with serial ultrasound (US) examinations. Sonography-based Automated Volume Count (SonoAVC) is a relatively new three-dimensional (3D) US technology, which automatically generates a set of measurements including the mean follicular diameter (MFD) and a volume-based diameter (d(V)) for each follicle in the ovaries. The present study aimed to assess the applicability and reproducibility of this automated follicle measurement method in an IVF programme. Methods: For this prospective method comparison study, 100 women undergoing US monitoring of a controlled ovarian stimulation cycle were recruited. Each follicle was manually measured by taking the mean of maximal diameters on three orthogonal planes with two-dimensional (2D) US. A 3D volume of each ovary was then captured. The ovarian volumes were later analysed using SonoAVC. The agreement between the two methods for the numbers of follicles and the size of the leading follicle was assessed with the Bland-Altman method. The reproducibility of SonoAVC measurements was assessed with the intraclass correlation coefficient (ICC). Results: Both SonoAVC-generated MFD and d(V)-based follicle counts, as well as the leading follicle diameter, had good agreement with conventional 2D US measurements. SonoAVC measurements had very good reproducibility, with ICC ≥0.8 for most evaluations. Conclusions: Automated follicle monitoring with SonoAVC can replace or be used interchangeably with conventional 2D measurements. Automated follicle monitoring can save time, provide a method of quality control and create opportunities for developing HCG criteria based on follicular volume or for monitoring patients from a distance. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness and safety of dual renin-angiotensin system (RAS) blockage together with total embryo cryopreservation for prevention of ovarian hyperstimulation syndrome (OHSS) in overstimulated patients undergoing IVF. Design: Retrospective case series. Setting: A private tertiary care hospital assisted reproduction program. Patient(s): Ten women at high risk for OHSS (mean E2 level 9401 ± 585 pg/mL on the day of hCG administration). Intervention(s): Cancellation of ET and dual RAS blockage with an angiotensin receptor blocker (candesartan cilexetil) and an angiotensin-converting enzyme inhibitor (enalapril) starting from day 1 after oocyte retrieval. Embryos were cryopreserved and transferred in subsequent cycles. Main Outcome Measure(s): Development of OHSS and pregnancy and live birth rates after frozen-thawed ETs. Result(s): While eight women did not develop OHSS, two women (20%) developed severe OHSS requiring hospitalization. Subsequent frozen-thawed ETs resulted in an 80% clinical pregnancy rate and 40% live birth rate. Conclusion(s): Dual RAS blockage with total embryo cryopreservation is a relatively new strategy that was proposed for use in patients at high risk for OHSS. It should be stressed that complete elimination of the syndrome is not possible with this treatment. Subsequent pregnancy rates with the transfer of frozen-thawed embryos are high. [Copyright &y& Elsevier]

Dysbiosis in the genital tract or gut microbiome can be associated with endometriosis. We sampled vaginal, cervical and gut microbiota from 14 women with histology proven stage 3/4 endometriosis and 14 healthy controls. The V3 and V4 regions of the 16S rRNA gene were amplified following the 16S Metagenomic Sequencing Library Preparation. Despite overall similar vaginal, cervical and intestinal microbiota composition between stage 3/4 endometriosis group and controls, we observed differences at genus level. The complete absence of Atopobium in the vaginal and cervical microbiota of the stage 3/4 endometriosis group was noteworthy. In the cervical microbiota, Gardnerella, Streptococcus, Escherichia, Shigella, and Ureoplasma, all of which contain potentially pathogenic species, were increased in stage 3/4 endometriosis. More women in the stage 3/4 endometriosis group had Shigella/Escherichia dominant stool microbiome. Further studies can clarify whether the association is causal, and whether dysbiosis leads to endometriosis or endometriosis leads to dysbiosis. [ABSTRACT FROM AUTHOR]

Progestins are capable of suppressing endogenous luteinizing hormone (LH) secretion from the pituitary; are less expensive than GnRH analogues. This systematic review summarizes the effectiveness of progestins as compared with GnRH analogues and identifies some of the future research perspectives. Several public resources were screened with a combination of keywords related to assisted reproductive technology, progesterone, GnRH analogue and ovarian stimulation. Overall, duration of stimulation, gonadotropin consumption and oocyte yield were similar with progestins and GnRH analogues. The live birth, ongoing and clinical pregnancy rates per embryo transfer were similar with progestins and GnRH analogues. There is still a low quality of evidence. Available information is reassuring regarding obstetric and neonatal outcomes with the use of progestins. As a wider implication, progestins can present an effective option for women who do not contemplate a fresh embryo transfer, anticipated hyper responders, preimplantation genetic testing, oocyte donors, double stimulation cycles. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic created a significant impact on medically assisted reproduction (MAR) services. ESHRE decided to mobilize resources in order to collect, analyse, monitor, prepare and disseminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) knowledge specifically related to ART and early pregnancy. This article presents the impact of the SARS-CoV-2 pandemic focusing on reproductive healthcare. It details the rationale behind the guidance prepared to support MAR services in organizing and managing the re-start of treatments or in case of any future wave of COVID-19 disease. The guidance includes information on patient selection and informed consent, staff and patient triage and testing, adaptation of ART services, treatment planning and code of conduct. The initiatives detailed in this article are not necessarily COVID-specific and such action plans could be applied effectively to manage similar emergency situations in different areas of medicine, in the future. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Assisted reproductive technology and intrauterine inseminations in Europe, 2005: results generated from European registers by ESHRE," by A. Andersen Nyboe and colleagues, published in a 2009 issue of the journal.

To date, recurrent implantation failure (RIF) has no clear definition and no clearly identified impaired function. Hence, the term RIF is currently used somewhat haphazardly, on the basis of clinicians' judgment. International experts in reproductive medicine met on July 1, 2022, in Lugano, Switzerland, to review the different facets of RIF and define the diagnosis and its appropriate management. A systematic review without meta-analysis of studies published in English from January 2015 to May 2022. Data indicated that RIF has been largely overevaluated, overdiagnosed, and overtreated without sufficient critical assessment of its true nature. Our analyses show that true RIF is extremely uncommon—occurring in <5% of couples with infertility—and that reassurance and continued conventional therapies are warranted in most cases of assisted reproductive technology (ART) failure. Although the true biologic determinants of RIF may exist in a small subset of people with infertility, they elude the currently available tools for assessment. Without identification of the true underlying etiology(ies), it is reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid blastocyst transfers (or the equivalent number of unscreened embryo transfers, adjusted to the patient's age and corresponding euploidy rate). In addition, other factors should be ruled out that may contribute to her reduced odds of sustained implantation. In such cases, implantation failure should not be the only issue considered in case of ART failure because this may result from multiple other factors that are not necessarily repetitive or persistent. In reality, RIF impacting the probability of further ART success is a very rare occurrence. True RIF is extremely uncommon, occurring in <5% of couples with infertility. Reassurance and continued conventional therapies are warranted in most cases. It would seem reasonable not to assign this diagnosis to a patient until she has failed at least 3 euploid embryo transfers (or the equivalent number of unscreened embryos, adjusted to her age). Given the number of internationally recognized experts in the field present at the Lugano meeting 2022, our publication constitutes a consensus statement. [ABSTRACT FROM AUTHOR]

Objective: To estimate whether intravenous immunoglobulin (IVIG) improves the probability of a live birth in women with unexplained recurrent miscarriage (RM). Design: A computerized search in Medline, Embase, Central, Ovid Medline In-Process, and Other Non-Indexed Citations Databases and randomized controlled trial (RCT) registries was performed. Abstracts of the American Society of Reproductive Medicine and European Society of Human Reproduction and Embryology annual meetings and reference lists of identified reports were searched. Setting: None. Patient(s): Women with unexplained primary (without a prior live birth) or secondary (subsequent to a live birth) RM. Intervention(s): IVIG or placebo control intervention. Main Outcome Measure(s): Live birth rate per randomized woman. Result(s): Six relevant RCTs were identified including 272 women with unexplained RM. The overall odds ratio for live birth is 0.92, with a 95% confidence interval of 0.55–1.54, indicating a lack of a treatment effect with IVIG. Similarly, IVIG was not found to be beneficial when women with primary and secondary RM were analyzed separately. Conclusion(s): A beneficial effect of IVIG in treatment of RM was not observed. Given the absence of a proven mechanism of action, and the lack of a diagnostic algorithm to identify patients who are likely to benefit from such treatment, IVIG administration for treatment of recurrent miscarriage is not justified outside the context of properly designed RCTs. [Copyright &y& Elsevier]

Objective: To describe a case of moderate ovarian hyperstimulation syndrome (OHSS) that was treated with high dose cabergoline. Design: Case report. Setting: Private assisted reproduction center. Patient(s): A 29-year-old woman who developed early moderate OHSS despite preventive cabergoline administration (0.5 mg/day) following controlled ovarian hyperstimulation for IVF treatment. Intervention(s): Cabergoline dose was increased to 1 mg/day upon diagnosis of OHSS on the second day after oocyte collection and embryo transfer was postponed to the fifth day after oocyte collection. Main Outcome Measure(s): Resolution of OHSS and achievement of healthy live birth. Result(s): OHSS resolved rapidly despite occurrence of pregnancy and patient delivered a healthy boy at term. Conclusion(s): The higher cabergoline dose might have prevented an increase in the severity of OHSS and its prolongation following occurrence of pregnancy. Randomized controlled trials assessing the efficacy and safety of different doses and durations of cabergoline administration in both prophylactic and therapeutic settings are required. [Copyright &y& Elsevier]

We consider data transmission through a time-selective, correlated (first-order Markov) Rayleigh fading channel subject to an average power constraint. The channel is estimated at the receiver with a pilot signal, and the estimate is fed back to the transmitter. The estimate is used for coherent demodulation, and to adapt the data and pilot powers. We derive the Hamilton--Jacobi--Bellman (HJB) equation for the optimal policy in a continuous-time limit where the channel state evolves as an Ornstein--Uhlenbeck diffusion process, and is estimated by a Kalman filter at the receiver. Finding an explicit solution to the HJB equation, as well as proving that a (twice-differentiable) solution exists, appears to be quite challenging. However, assuming that such a solution does exist, we explicitly determine the optimal pilot and data power control policies. The optimal pilot policy switches between zero and the maximum (peak-constrained) value (“bang-bang” control), and approximates the optimal discrete-time policy at low signal-to-noise ratios (SNRs) (equivalently, large bandwidths). The switching boundary is defined in terms of the system state (estimated channel mean and associated error variance), and can be explicitly computed. Under the optimal policy, the transmitter conserves power by decreasing the training power when the channel is faded, thereby increasing the data rate. Numerical results show a significant increase in achievable rate due to the adaptive training scheme with feedback, relative to constant (nonadaptive) training, which does not require feedback. The gain is more pronounced at relatively low SNRs and with fast fading. Results are further verified through Monte Carlo simulations. [ABSTRACT FROM PUBLISHER]

Objective: To analyze whether the use of a hyaluronan-enriched transfer medium (HETM) increases rates of implantation (IRs) and clinical pregnancy (CPRs), compared with the use of a conventional transfer medium after day 3 and day 5 embryo transfers. Design: Prospective randomized controlled trial. Setting: An assisted reproduction program in a private tertiary-care hospital in Turkey. Patient(s): A total of 1,282 consecutive fresh embryo transfer cycles (825 day 3 and 457 day 5) were randomly allocated into two groups. In 639 women, ET was effected with HETM, and in 643, it was effected with a conventional embryo transfer medium. Intervention(s): Embryo transfer using HETM or conventional embryo transfer medium. Main Outcome Measure(s): Clinical pregnancy rates and IRs were compared with regard to day of embryo transfer, women''s age, quality of the transferred embryos, and presence of previous implantation failures. Result(s): Overall CPRs and IRs significantly increased with the use of HETM (CPR: 54.6% vs. 48.5%, odds ratio: 1.28, 95% confidence interval: 1.03–1.59; IR: 32% vs. 25%, odds ratio: 1.43, 95% confidence interval: 1.23–1.66, for HETM and control groups, respectively). The number needed to treat (NNT) for one additional pregnancy with routine use of HETM was 17. The beneficial effect was more prominent in women who were >35 years of age (NNT = 7), in women who had previous failed cycles (NNT = 7), and in women who had poor-quality embryos (NNT = 8). Conclusion(s): The enrichment of transfer medium with hyaluronan increases CPRs and IRs, both for day 3 and day 5 embryo transfers. The beneficial effect was most evident in women who were >35 years of age, in women who had only poor-quality embryos available for transfer, and in women who had previous implantation failures. [Copyright &y& Elsevier]

Background: This study compared outcomes of the standard 6000 IU human chorionic gonadotropin (hCG) trigger with a dual trigger comprised of 6000 IU hCG and 1 mg leuprolide acetate for final oocyte maturation in an intracytoplasmic sperm injection (ICSI) cycle. By convention, ICSI was performed in most cases at the clinic. Materials and Methods: In this retrospective study, a total of 50 women were included in each arm. Participants were matched for age, indication and number of prior assisted reproduction technology (ART) cycles. Women at risk for ovarian hyperstimulation syndrome (OHSS) were excluded. A flexible gonadotropin releasing hormone (GnRH) antagonist protocol was used and final oocyte maturation was triggered when two leading follicles were >17 mm. Distribution of variables was evaluated visually with histograms. Continuous variables were defined by mean (standard deviation) or median (25th-75th percentile) depending on distribution characteristics. Categorical variables were defined by numbers and percentages. Continuous variables were compared between the groups with the t test or Mann-Whitney U test as appropriate. Categorical variables were compared by the chi-square test and its derivatives as appropriate. A two-sided P<0.05 indicated statistical significance. Results: Both groups had similar antral follicle counts, median parity (0) and number of previous failed cycles (0). The median number of oocytes (8 vs. 7), metaphase-two oocytes (6 vs. 5.5), blastocysts (1 vs. 1), clinical pregnancy rates (CPR) (28% vs. 22%), ongoing pregnancy rates (OPR) (22% vs. 20%) and pregnancy rate per transfer (53.3% vs 53.8%) were similar between the dual trigger and hCG only groups, respectively. Conclusion: Dual trigger for oocyte maturation stimulation failed to improve the ICSI outcome. [ABSTRACT FROM AUTHOR]

Objective: To investigate the predictive value of endometrial thickness (EMT) for live birth when a lower threshold of EMT is not employed for embryo transfer (ET).Design: Retrospective study SETTING: Academic assisted reproduction center PATIENT(S): All women who underwent fresh or frozen-thawed ET at the Koç University Hospital Assisted Reproduction Unit between October 2016 and August 2019 INTERVENTION(S): After ruling out endometrial pathology, blastocyst transfer was planned regardless of the EMT in the absence of increased serum progesterone level on the trigger day in fresh embryo transfer cycles or before commencing progesterone treatment in artificially prepared frozen-thawed ET cycles.Main Outcome Measure(s): The primary outcome was live birth. Live birth and miscarriage rates per ET were stratified according to fresh and frozen-thawed ET cycles for each millimeter of endometrial thickness. Receiver operator characteristic curve analyses were performed to evaluate the predictive value of EMT for live birth.Result(s): A total of 560 ET cycles, 273 fresh and 287 frozen-thawed, were included in the study. Relevant patient characteristics as well as EMTs were similar between women who achieved a live birth and those who did not after fresh or frozen-thawed ET. There was no linear association between EMT and live birth or miscarriage rates. Area under the curve values for EMT to predict live birth after fresh, frozen-thawed, and all ETs were 0.56, 0.47, and 0.52, respectively.Conclusion(s): Our results showed that the EMT was not predictive for live birth in either fresh or frozen-thawed ET cycles. Once intracavitary pathology and inadvertent progesterone exposure were excluded, women with thinner EMTs should not be denied their potential for live birth because it is comparable to that of those with thicker EMT. [ABSTRACT FROM AUTHOR]

We aimed to answer one key question, that was not previously addressed as to whether serum progesterone (P4-hCG day) and its co-variates (estradiol (E2-hCG day) and the number of retrieved oocytes) of a given cycle can be predictive of the subsequent cycle when both cycles are consecutive and comparable for the stimulation protocol, gonadotropin dose and duration of stimulation. We analyzed such 244 consecutive (< 6 months) IVF cycles in 122 patients with GnRH agonist long protocol and found that P4, E2 and the number of retrieved oocytes significantly vary between the two cycles. Although P4 increased (ranging from 4.7 to 266.7%) in the 2nd cycle in 61 patients, E2 and the number of retrieved oocytes, which are normally positively correlated with P4 paradoxically decreased in the 41% and 37.7% respectively, of these same 61 patients. When a similar analysis was done in the 54 out of 122 patients (44.3%) in whom serum P4 was decreased in the 2nd cycle, the mean decrease in P4 was − 34.1 ± 23.3% ranging from − 5.26 to − 90.1%. E2 and the number of retrieved oocytes paradoxically increased in the 42.3% and 40.7% of these 54 patients respectively. P4 remained the same only in the 7 (5.7%) of these 122 patients. These findings indicate that late follicular phase serum P4 may change unpredictably in the subsequent IVF cycle. The changes are not always necessarily proportional with ovarian response of previous cycle suggesting that growth characteristics and steroidogenic activities of antral cohorts may exhibit considerable cycle to cycle variations. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a flexible progestin primed ovarian stimulation (fPPOS) protocol is effective for preventing premature ovulation.Design: Retrospective cohort study.Setting: Private assisted reproduction center.Patient(s): Eighty-seven oocyte donors and 191 recipients of fresh oocytes.Intervention(s): Each donor was stimulated with a flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in one cycle and with the new fPPOS protocol in the other, within a period of 6 months. FSH was started on cycle day 2-3, and 0.25 mg/day GnRH antagonist or 10 mg/day medroxyprogesterone acetate (MPA) was started on stimulation day 7 or when the leading follicle reached 14 mm, whichever came first.Main Outcome Measure(s): Duration of stimulation, gonadotropin consumption, duration of GnRH antagonist or MPA administration, number of metaphase II oocytes, and pregnancy rates in fresh oocyte recipients.Results: Duration of stimulation was 11 (10-11) days in both groups. Total gonadotropin consumption was similar. Pituitary suppression was started on day 7 and lasted for 5 days in each group. There were no premature ovulations in any group. The fPPOS yielded a significantly higher number of cumulus oocyte complexes than GnRH antagonist cycles (33 [21-39] vs. 26 [18-36], respectively). Likewise, the fPPOS generated significantly more metaphase II oocytes than GnRH antagonist cycles (24 [17-34] vs. 21 [15-28], respectively). Recipients of fresh oocytes from fPPOS and GnRH antagonist cycles had similar cleavage, blastulation, implantation, and live birth/ongoing pregnancy rates (50% vs. 48.6%).Conclusion(s): FPPOS with MPA seems to be an effective choice for preventing premature ovulation in women undergoing ovarian stimulation without compromising oocyte quality. [ABSTRACT FROM AUTHOR]

Objective(s): To analyze whether first-degree relatives (FDR) of patients with polysystic ovary syndrome (PCOS) have an increased risk of insulin resistance and glucose intolerance.Design: Systematic review and meta-analysis.Setting: None.Patient(s): Parents and siblings of women with and without PCOS.Intervention(s): Search of PubMed database from 1960 to September 2017 with cross-checking of references of relevant articles in English.Main Outcome Measure(s): Prevalence of type 2 diabetes mellitus (T2DM) and impaired glucose tolerance, and levels of fasting insulin, 2-hour insulin levels, and homeostatic model assessment insulin resistance (HOMA IR).Result(s): Our search retrieved 4,796 articles of which 19 were included. The prevalence of T2DM was significantly increased in mothers and fathers of PCOS probands (rate ratio [RR] 2.43; 95% confidence interval [CI], 1.58-3.75, and RR 2.27; 95% CI, 1.25-4.12). Moreover, the fasting insulin (in mothers, fathers, and sisters) and HOMA IR (in mothers, fathers, and sisters) levels were statistically significantly higher in parents and siblings of PCOS patients. The sisters (RR 1.34; 95% CI, 0.59-3.03) and brothers (RR 1.51; 95% CI, 0.63-3.62) had a higher prevalence of T2DM than the control subjects, but the difference was not statistically significant.Conclusion(s): Our meta-analysis provides quantitative evidence demonstrating clustering of T2DM and insulin resistance in the parents and siblings of PCOS probands.Systematic Review Registration Number: PROSPERO 2016 CRD42016048551. [ABSTRACT FROM AUTHOR]

Study Question: Are there any differences in the molecular characteristics of the luteal granulosa cells (GC) obtained from stimulated versus non-stimulated (natural) IVF cycles that may help explain the defective luteal phase in the former?Summary Answer: Luteal GC of stimulated IVF cycles, particularly those of agonist-triggered antagonist cycles, are less viable ex vivo, express LH receptor and anti-apoptotic genes at lower levels, undergo apoptosis earlier and fail to maintain their estradiol (E2) and progesterone (P4) production in comparison to natural cycle GC.What Is Known Already: Luteal function is defective in stimulated IVF cycles, which necessitates P4 and/or hCG administration (known as luteal phase support) in order to improve clinical pregnancy rates and prevent miscarriage. The luteal phase becomes shorter and menstruation begins earlier than a natural cycle if a pregnancy cannot be achieved, indicative of early demise of corpus luteum (premature luteolysis). Supra-physiological levels of steroids produced by multiple corpora luteae in the stimulated IVF cycles are believed to inhibit LH release directly via negative feedback actions on the hypothalamic-pituitary-ovarian axis resulting in low circulating levels of LH and a defective luteal phase. We hypothesized that some defects in the viability and steroidogenic activity of the luteal GC of the stimulated IVF cycles might contribute to this defective luteal phase in comparison to natural cycle GC. This issue has not been studied in human before.Study Design, Size, Duration: A comparative translational research study of ex vivo and in vitro models of luteal GC recovered from IVF patients undergoing natural versus stimulated IVF cycles was carried out. Luteinized GC were obtained from 154 IVF patients undergoing either natural (n = 22) or stimulated IVF cycles with recombinant FSH and GnRH agonist (long) (n = 44), or antagonist protocol triggered conventionally either with recombinant hCG (n = 46) or with a GnRH agonist (n = 42). GC were maintained in vitro for up to 6 days.Participants/materials, Setting, Methods: Cellular viability (YO-PRO-1 staining), the expression of the steroidogenic enzymes, pro-apoptotic genes [Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX) and Caspase-3 (CASP3)], anti-apoptotic genes [RAC-alpha serine/threonine-protein kinase (AKT-1) and Bcl-2-like protein 2 (BCL2-L2)], LH receptor, vascular endothelial growth factor (VEGF) (using real-time quantitative PCR at mRNA level and western blot immunoprecipitation assay at protein level) and in vitro E2 and P4 production (electrochemiluminescence immunoassay) were compared in GC among the groups.Main Results and the Role Of Chance: Natural cycle GC were significantly more viable ex vivo (88%) compared to their counterparts of the stimulated IVF cycles (66, 64 and 37% for agonist and antagonist cycles triggered with hCG and GnRH agonist respectively, P < 0.01). They were also more capable of maintaining their vitality in culture compared to their counterparts from the stimulated IVF cycles: at the end of the 6-day culture period, 74% of the cells were still viable whereas only 48, 43 and 22% of the cells from the agonist and antagonist cycles triggered with hCG and agonist respectively, were viable (P < 0.01). The mRNA expression of anti-apoptotic genes (AKT-1 and BCL2-L2) was significantly lower, while that of pro-apoptotic genes (BAD, BAX and CASP3) was significantly higher in the stimulated cycles, particularly in the agonist-triggered antagonist cycles, compared to natural cycle GC (P < 0.01 for long protocol and antagonist hCG trigger, P < 0.001 for agonist trigger). The expression of steroidogenic enzymes (stAR, SCC, 3β-HSD and aromatase) and VEGF was significantly higher in the agonist and hCG-triggered antagonist cycles compared to natural cycle GC. Therefore, in vitro E2 and P4 production in cells from the stimulated IVF cycles was significantly higher than their counterparts obtained from the natural cycles in the first 2 days of culture. However, after Day 2, their viability and hormone production began to decline very rapidly with the most drastic decrease being observed in the agonist-triggered cycles. By contrast, natural cycle GC maintained their viability and produced E2 and P4 in increasing amounts in culture up to 6 days. In vitro P production and the mRNA and protein expression of LH receptor, VEGF and 3β-HSD were most defective in the agonist-triggered antagonist cycles compared to natural and agonist and hCG-triggered antagonist cycles. In vitro hCG treatment of a subset of the cells from the agonist-triggered cycles improved their viability, increased E2 and P4 production in vitro and up-regulated the mRNA expression of anti-apoptotic gene BCL-L2 together with steroidogenic enzymes stAR, SCC, 3B-HSD, LH receptor and VEGF.Large Scale Data: Not applicable.Limitations, Reasons For Caution: The limitations include analysis of luteinized GC only might not reflect the in vivo mechanisms involved in survival and function of the whole corpus luteum; GC recovered during oocyte retrieval belong to a very early stage of the luteal phase and might not be representative; effects of ovulation triggered with hCG may not equate to the endogenous LH trigger; the clinical characteristics of the patients may vary among the different groups and it was not possible to correlate stimulation-related molecular alterations in luteal GC with the clinical outcome, as no oocytes have been utilized yet. Therefore, our findings do not conclusively rule out the possibility that some other mechanisms in vivo may also account for defective luteal function observed in stimulated IVF cycles.Wider Implications Of the Findings: Ovarian stimulation is associated with significant alterations in the viability and steroidogenic activity of luteal GC depending on the stimulation protocol and mode of ovulation trigger. Reduced survival and down-regulated expression of 3B-HSD, LH receptor and VEGF leading to compromised steroid production in stimulated cycles, and particularly in the agonist-triggered cycles, may at least in part help explain why the luteal phase is defective and requires exogenous support in these cycles.Study Funding/competing Interest(s): This study was funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

We performed a literature review of studies comparing the effectiveness of progestins in preventing premature ovulation during ovarian stimulation for assisted reproductive technology (ART). Five randomized trials and cohort studies involving a total of 2404 women, which compared; i) two different progestins or ii) two different doses of the same progestin were included. The primary outcome was live birth rate (LBR) per woman. Secondary outcomes were live birth or ongoing pregnancy (LB/OP) per woman and per embryo transfer (ET), ongoing pregnancy, clinical pregnancy, positive pregnancy test, numbers of oocytes and metaphase-two oocytes, duration of stimulation and gonadotropin consumption. The primary outcome was not reported in most studies however there were no differences between progestins for secondary outcomes. All progestins seem to effectively prevent premature ovulation in ART cycles. Low-quality evidence suggests that progestins can effectively prevent premature ovulation in ART cycles. [ABSTRACT FROM AUTHOR]

We performed a literature review of studies comparing the effectiveness of progestins in preventing premature ovulation during ovarian stimulation for assisted reproductive technology (ART). Five randomized trials and cohort studies involving a total of 2404 women, which compared; i) two different progestins or ii) two different doses of the same progestin were included. The primary outcome was live birth rate (LBR) per woman. Secondary outcomes were live birth or ongoing pregnancy (LB/OP) per woman and per embryo transfer (ET), ongoing pregnancy, clinical pregnancy, positive pregnancy test, numbers of oocytes and metaphase-two oocytes, duration of stimulation and gonadotropin consumption. The primary outcome was not reported in most studies however there were no differences between progestins for secondary outcomes. All progestins seem to effectively prevent premature ovulation in ART cycles. Low-quality evidence suggests that progestins can effectively prevent premature ovulation in ART cycles. [ABSTRACT FROM AUTHOR]

Objective: To provide an evidence-based assessment of metabolic syndrome, hypertension, and hyperlipidemia in first-degree relatives of women with polycystic ovary syndrome (PCOS).Design: Systematic review and meta-analysis.Setting: Not applicable.Patient(s): Mothers, fathers, sisters, and brothers of women with and without PCOS.Intervention(s): An electronic-based search with the use of PubMed from 1960 to June 2015 and cross-checked references of relevant articles.Main Outcome Measure(s): Metabolic syndrome, hypertension and dyslipidemia, and surrogate markers, including systolic blood pressure (BP), diastolic BP, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides.Result(s): Fourteen of 3,346 studies were included in the meta-analysis. Prevalence of the following was significantly increased in relatives of women with PCOS: metabolic syndrome (risk ratio [RR] 1.78 [95% confidence interval 1.37, 2.30] in mothers, 1.43 [1.12, 1.81] in fathers, and 1.50 [1.12, 2.00] in sisters), hypertension (RR 1.93 [1.58, 2.35] in fathers, 2.92 [1.92, 4.45] in sisters), and dyslipidemia (RR 3.86 [2.54, 5.85] in brothers and 1.29 [1.11, 1.50] in fathers). Moreover, systolic BP (mothers, sisters, and brothers), total cholesterol (mothers and sisters), low-density lipoprotein cholesterol (sisters), and triglycerides (mothers and sisters) were significantly higher in first-degree relatives of PCOS probands than in controls.Conclusion(s): Our results show evidence of clustering for metabolic syndrome, hypertension, and dyslipidemia in mothers, fathers, sisters, and brothers of women with PCOS.Systematic Review Registration Number: PROSPERO 2016 CRD42016048557. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical outcome of single-embryo transfer (SET) with double-embryo transfer (DET) in in vitro maturation (IVM) cycles performed in patients with polycystic ovary syndrome (PCOS), and to determine which factors predict those outcomes.Design: A retrospective analysis.Setting: Private assisted reproduction center.Patient(s): One hundred and fifty-nine women with PCOS.Intervention(s): In vitro maturation with elective SET or DET conducted between September 2007 and May 2014.Main Outcome Measure(s): Live-birth rates.Result(s): Single-embryo transfer was performed in 83 patients (52.2%), and DET was performed in 76 patients (47.7%). When compared with the patients who had DET, the patients who had SET were statistically significantly younger (32.4 ± 3.5 vs. 24.1 ± 4.2 years) and had a shorter infertility duration (9.2 ± 4.5 vs. 4.4 ± 2.1 years), fewer previous ART cycles (<2 prior attempts, 39.5% vs. 6%; ≥2 prior attempts, 60.5% vs. 0), fewer collected oocytes (15.1 ± 4.6 vs. 12.6 ± 3.8), fewer metaphase II oocytes (9.0 ± 4.1 vs. 5.7 ± 2.9), fewer fertilized oocytes (8.2 ± 3.7 vs. 3.6 ± 2.3), and a higher implantation rate (27% vs. 47%). The SET and DET groups had similar embryo quality and similar clinical pregnancy (44.6% vs. 44.7%) and live-birth rates (34.9% vs. 34.2%). Twin pregnancy rates were statistically significantly higher in the DET compared with the SET groups (9.2% vs. 2.4%).Conclusion(s): In vitro maturation is a successful assisted reproduction technique that can be an alternative to conventional in vitro fertilization in women presenting with PCOS-related infertility. Our observations suggest that SET is a feasible option to prevent multiple pregnancies while maintaining the live-birth rate. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to determine whether high E2 levels after controlled ovarian hyperstimulation affect TSH. Methods: Patients completing ART cycles between April-October 2010 were eligible for this cohort study. 180 patients were recruited however those with known thyroid disease were excluded. The final analysis included 154 subjects. Blood was collected at each visit during the ART cycle as well as at the pregnancy test. Samples were frozen at −20 °C and analyzed together for E2 and TSH using the same assay kit once all patients had completed their cycles. All participants were treated at the McGill University Health Center. A paired t-test was used to study the difference in TSH levels recorded at maximal and minimal Estradiol levels during ovarian stimulation. Multiple regression analysis was then used to determine if factors such as anti-thyroid antibodies and ovarian reserve measures affect this change in TSH. We used multiple imputation methods to account for missing data. Results: As E2 levels rose from low to supra-physiologic levels during treatment, TSH levels also rose significantly. This increase was clinically significant by the time of pregnancy test. The factors that potentially affected the change in TSH were: male factor/tubal factor infertility, type of protocol used as well as the presence of thyroid antibodies. Conclusions: Although TSH increases during ART, this change only becomes clinically significant on the day of pregnancy test. Future studies should examine TSH changes specifically in certain “at-risk” sub-groups such as those with antibodies and known thyroid disease. [ABSTRACT FROM AUTHOR]