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STUDY QUESTION What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation? SUMMARY ANSWER The fourth and fifth euploid blastocyst transfers resulted in similar live birth rates of 40% and 53.3%, respectively, culminating in a cumulative live birth rate of 98.1% (95% CI = 96.5–99.6%) after five euploid blastocyst transfers. WHAT IS KNOWN ALREADY The first three euploid blastocysts have similar implantation and live birth rates and provide a cumulative live birth rate of 92.6%. STUDY DESIGN, SIZE, DURATION An international multi-center retrospective study was conducted at 25 individual clinics. The study period spanned between January 2012 and December 2022. A total of 123 987 patients with a total of 64 572 euploid blastocyst transfers were screened for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients with a history of any embryo transfer at another clinic, history of any unscreened embryo transfer at participating clinics, parental karyotype abnormalities, the use of donor oocytes or a gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital uterine anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior to initiating of progesterone, use of testicular sperm due to non-obstructive azoospermia in the male partner, transfer of an embryo with a reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles for monogenic disorders, or structural chromosome rearrangements were excluded. Ovarian stimulation protocols and embryology laboratory procedures including trophectoderm biopsy followed the usual practice of each center. The ploidy status of blastocysts was determined with comprehensive chromosome screening. Endometrial preparation protocols followed the usual practice of participating centers and included programmed cycles, natural or modified natural cycles. MAIN RESULTS AND THE ROLE OF CHANCE A total of 105 (0.085% of the total population) patients met the criteria and underwent at least one additional euploid blastocyst transfer after failing to achieve a positive pregnancy test with three consecutive euploid blastocyst transfers. Outcomes of the fourth and fifth euploid blastocyst transfers were similar across participating centers. Overall, the live birth rate was similar with the fourth and fifth euploid blastocysts (40% vs 53.3%, relative risk = 1.33, 95% CI = 0.93–1.9, P value = 0.14). Sensitivity analyses excluding blastocysts biopsied on Day 7 postfertilization, women with a BMI >30 kg/m2, cycles using non-ejaculate or donor sperm, double-embryo transfer cycles, and cycles in which the day of embryo transfer was modified due to endometrial receptivity assay test result yielded similar results. Where data were available, the fourth euploid blastocyst had similar live birth rate with the first one (relative risk = 0.84, 95% CI = 0.58–1.21, P  = 0.29). The cumulative live birth rate after five euploid blastocyst transfers was 98.1% (95% CI = 96.5–99.6%). LIMITATIONS, REASONS FOR CAUTION Retrospective design has its own inherent limitations. Patients continuing with a further euploid embryo transfer and patients dropping out from treatment after three failed euploid transfers can be systematically different, perhaps with regard to ovarian reserve or economic status. WIDER IMPLICATION OF THE FINDINGS Implantation failure seems to be mainly due to embryonic factors. Given the stable and high live birth rates up to five euploid blastocysts, unexplained recurrent implantation failure should have a prevalence of <2%. Proceeding with another embryo transfer can be the best next step once a known etiology for implantation failure is ruled out. STUDY FUNDING/COMPETING INTEREST(s) None. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

A system manager makes dynamic pricing and dispatch control decisions in a queueing network model motivated by ride hailing applications. A novel feature of the model is that it incorporates travel times. Unfortunately, this renders the exact analysis of the problem intractable. Therefore, we study this problem in the heavy traffic regime. Under the assumptions of complete resource pooling and common travel time and routing distributions, we solve the problem in closed form by analyzing the corresponding Bellman equation. Using this solution, we propose a policy for the queueing system and illustrate its effectiveness in a simulation study. [ABSTRACT FROM AUTHOR]

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]

The article discusses a study on progestin-primed ovarian stimulation (PPOS) and its effects on aneuploidy (abnormal number of chromosomes) in blastocysts. The study compared two cycles in the same patients, one using a GnRH antagonist and the other using a PPOS protocol. The results showed similar rates of euploidy (normal number of chromosomes) between the two cycles, with slightly higher oocyte yield in the PPOS cycle. The article also addresses previous studies that have reported conflicting results on the effectiveness of PPOS, emphasizing the need for high-quality studies to determine its true impact. Overall, the study supports the use of PPOS as a safe and effective method for ovarian stimulation. [Extracted from the article]

The ultimate measure of success of assisted reproductive technology (ART) is the cumulative live birth rate (CLBR) per ovarian stimulation cycle, which increases with every oocyte collected. However, the adverse effects of ovarian stimulation on endometrial receptivity, as well as the risks of ovarian hyperstimulation syndrome (OHSS) and adverse obstetric and neonatal outcomes, are observed to increase with ovarian response to stimulation. To mitigate these risks, mild stimulation has been hailed as the safer patient-friendly approach with the additional benefit of cutting the cost of gonadotrophins. Yet accumulating data demonstrate the absence of an adverse effect of ovarian stimulation on oocytes as well as on obstetric and neonatal outcomes, and multiple preventive strategies have been introduced for OHSS. The widespread use of vitrification revolutionized ART by enabling the liberal use of cycle segmentation to minimize the risk of OHSS and avoid impaired endometrial receptivity due to ovarian stimulation. Vitrification also allowed every oocyte to contribute to the CLBR. Thus, it is questionable whether the cost savings from gonadotrophins during the index ovarian stimulation offset the cost saving by preventing repeat ovarian stimulation and repeat laboratory procedures per live birth. This paper aims to prove by contradiction that ovarian stimulation should be aimed to maximize oocyte yield. [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]

How endometriosis causes infertility, with the exception of tubal dysfunction caused by adhesions, is unclear. The inflammatory milieu in the pelvis and impaired receptivity of the eutopic endometrium are considered to be possible factors. Anatomical staging systems fail to predict the fertility status of endometriosis patients. Data from assisted reproductive technology cycles consistently suggest that oocytes from patients with endometriosis have a normal potential to develop into euploid blastocysts. Moreover, oocyte or embryo recipients with endometriosis seem to have similar or slightly lower pregnancy and live birth rates compared with recipients without endometriosis, suggesting that eutopic endometrium is not or is only minimally affected, which may be caused by undiagnosed adenomyosis. In-vivo observations from women with endometriomas provide evidence against a detrimental effect of endometriomas on oocytes. Combined with the absence of an obvious improvement in fertility following the surgical destruction or excision of peritoneal endometriosis or from temporary medical suppression of the disease and the associated inflammation, the available evidence makes endometriosis-associated infertility questionable in the absence of tubal dysfunction caused by adhesions. It is likely that no anatomical staging will correlate with fertility beyond assessing tubal function. In patients with endometriosis assisted reproductive technology is as effective as for other indications. [ABSTRACT FROM AUTHOR]

This paper studies a diffusion control problem motivated by challenges faced by public health agencies who run clinics to serve the public. A key challenge for these agencies is to motivate individuals to participate in the services provided. They must manage the flow of (voluntary) participants so that the clinic capacity is highly utilized, but not overwhelmed. The organization can deploy costly promotion activities to increase the inflow of participants. Ideally, the system manager would like to have enough participants waiting in a queue to serve as many individuals as possible and efficiently use clinic capacity. However, if too many participants sign up, resulting in a long wait, participants may become irritated and hesitate to participate again in future. We develop a diffusion model of managing participant inflow mechanisms. Each mechanism corresponds to choosing a particular drift rate parameter for the diffusion model. The system manager seeks to balance three different costs optimally: (i) a linear holding cost that captures the congestion concerns, (ii) an idleness penalty corresponding to wasted clinic capacity and negative impact on public health, and (iii) costs of promotion activities. We show that a nested-threshold policy for deployment of participant inflow mechanisms is optimal under the long-run average cost criterion. In this policy, the system manager progressively deploys mechanisms in increasing order of cost, as the number of participants in the queue decreases. We derive explicit formulas for the queue length thresholds that trigger each promotion activity, providing the system manager with guidance on when to use each mechanism. [ABSTRACT FROM AUTHOR]

Motivated by applications in queueing theory, we consider a class of singular stochastic control problems whose state space is the d-dimensional positive orthant. The original problem is approximated by a drift control problem, to which we apply a recently developed computational method that is feasible for dimensions up to d=30\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$d=30$$\end{document} or more. To show that nearly optimal solutions are obtainable using this method, we present computational results for a variety of examples, including queueing network examples that have appeared previously in the literature. [ABSTRACT FROM AUTHOR]

Progestin-primed ovarian stimulation (PPOS) is being increasingly used for ovarian stimulation in assisted reproductive technology. Different progestins have been used with similar success. The available studies suggest a similar response to ovarian stimulation with gonadotrophin-releasing hormone (GnRH) analogues. Any differences in the duration of stimulation or gonadotrophin consumption are minor and clinically insignificant. PPOS has the advantage of oral administration and lower medication costs than GnRH analogues. As such it is clearly more cost-effective for fertility preservation and planned freeze-all cycles, but when fresh embryo transfer is intended PPOS can be less cost-effective depending on the local direct and indirect costs of the additional initial frozen embryo transfer cycle. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analogue cycles seem to be similar in terms of both ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies have reported lower cumulative live birth rates with PPOS, they have methodological issues, including arbitrary definitions of the cumulative live birth rate. PPOS has been used in all patient types (except progesterone receptor-positive breast cancer patients) with consistent results and seems a patient friendly and cost-effective choice if a fresh embryo transfer is not intended. [ABSTRACT FROM AUTHOR]

Does the trigger to oocyte retrieval interval (TORI) affect oocyte maturation rates differently in progestin-primed ovarian stimulation (PPOS) and gonadotrophin-releasing hormone (GnRH) antagonist cycles? This was a retrospective cohort study. The interaction between the stimulation protocol and TORI was assessed in a linear mixed effects multivariable regression analysis with oocyte maturation rate as the dependent variable, and stimulation protocol (GnRH antagonist or PPOS), age (continuous), gonadotrophin type (FSH or human menopausal gonadotrophin), trigger (human chorionic gonadotrophin [HCG] or GnRH agonist), TORI (continuous) and days of stimulation (continuous) as the independent variables. Oocyte maturation rate was defined as number of metaphase II oocytes/number of cumulus–oocyte complexes retrieved. The maturation rate was calculated per cycle and treated as a continuous variable. A total of 473 GnRH antagonist and 205 PPOS cycles (121 conventional PPOS and 84 flexible PPOS) were analysed. The median (quartiles) female age was 36 (32–40) years. Of these cycles, 493 were triggered with HCG and 185 with a GnRH agonist. The TORI ranged between 33.6 and 39.1 h, with a median (quartiles) of 36.2 (36–36.4) hours. Maturation rates were similar between fixed PPOS, flexible PPOS and antagonist cycles (median 80%, 75% and 75%, respectively, P = 0.15). There was no significant interaction between the stimulation protocols and TORI for oocyte maturation. PPOS cycles do not seem to require a longer TORI than GnRH antagonist cycles. [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]

In this paper, a decoupled backstepping sliding mode control method is proposed to control underactuated systems under uncertainties and disturbances. The sliding mode control technique and the backstepping control technique are combined owing to their merits. Since the design methodology is based on the Lyapunov theorem, the stability of the system is guaranteed. The effectiveness of the proposed method is verified by the experimental results of the controller which is applied to a nonlinear, underactuated inverted pendulum system. The experimental results show that the decoupled backstepping sliding mode control achieves a satisfactory control performance rather than the decoupled sliding mode controller and the proposed method provides a robust performance to overcome parametric uncertainties where the decoupled sliding mode control fails. [ABSTRACT FROM AUTHOR]

Ovarian stimulation for assisted reproductive technology is traditionally started in the early follicular phase. The essential rationale is to allow timely follicle growth and oocyte retrieval to ensure synchronization of the in-vitro cultured embryos with the receptive period of the endometrium in a fresh transfer cycle. In addition, conventional thought suggested that follicle recruitment happened only once, around menstruation. A deeper understanding of folliculogenesis, advances in cryobiology and an increasing proportion of freeze-all cycles provide a unique opportunity here. Experience from oncofertility patients as well as infertile women and oocyte donors who underwent ovarian stimulation in different phases of the menstrual cycle, dubbed 'random start' cycles, suggests that the number of oocytes collected and their reproductive potential do not depend on the time of starting ovarian stimulation, although the duration of stimulation and gonadotrophin consumption can vary slightly. It may be time to free both patients and clinics from the obsession with starting ovarian stimulation in the early follicular phase in planned freeze-all cycles. The flexibility provided by random start cycles is one aspect of individualizing treatment to patients' needs. [ABSTRACT FROM AUTHOR]

Objective: To compare dual oocyte retrieval with minimal ovarian stimulation and embryo transfer in the same menstrual cycle versus conventional ovarian stimulation among women with premature ovarian insufficiency (POI).Methods: A retrospective study of 51 women with POI attending a reproductive center in Turkey between 2013 and 2015. Women with an ovarian follicle of 12 mm or larger early in the follicular phase who underwent oocyte retrieval followed by an immediate cycle of ovarian stimulation (group 1, n=14) were compared with those who received conventional ovarian stimulation (group 2, n=37). Both groups underwent subsequent ovarian stimulation cycles to obtain optimally two embryos for transfer.Results: The groups had similar baseline parameters. Serum estradiol was higher in group 1 (P<0.001); total number of oocyte retrievals was higher in group 2 (P<0.001); and total number of oocytes retrieved was similar (P=0.192). Group 1 had more higher-quality embryos (P=0.031). There was a non-significant trend toward higher live birth rates in the dual trigger group (28% vs 8%, P=0.08).Conclusion: Rescuing growing follicles early in the follicular phase combined with subsequent ovarian stimulation and embryo transfer in the same cycle resulted in fewer oocyte retrieval cycles and might potentially improve reproductive outcomes. [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]

In this retrospective multicenter cohort study, women with congenital hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic sperm injection in-between 2010–2014 were compared to age-matched controls with tubal factor infertility (n = 114) to assess ovarian stimulation cycle and pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6% in CHH and controls groups, respectively (p = 0.36). Comparable success rates were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78–2.67,p = 0.24). Of the 57 women with CHH, 19 were stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH-agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25 cases. Compared to women with PS, women without PS had significantly higher embryo implantation rates (21.6 versus 52.6%,p = 0.03). Although there was a trend favoring no PS, LBRs (25.0 versus 40.0%,p = 0.26) per cycle were short of statistical significance. LBRs per cycle (57.1 versus 31.2%,p = 0.11) and miscarriage rates (11.1 versus 16.7%,p = 0.75) were similar between CHH women who were given estrogen + progesterone and progesterone alone to support the luteal phase. In conclusion, the optimal stimulation protocol appears to be exogenous gonadotropin stimulation alone, without PS, and progesterone-only luteal phase support in CHH patients. [ABSTRACT FROM PUBLISHER]

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]

This paper studies a Geo/Geo/1 $$+GI$$ queue in which the abandonments are endogenous. One crucial feature of this model is that the abandonment behavior is affected by the system performance and vice versa. Our model captures this interaction by developing two closely related models: an abandonment model and a queueing model. In the abandonment model, customers take the virtual waiting time distribution as given. They receive a reward r from service and incur a cost c per period of waiting. Customers are forward-looking and maximize their expected discounted utilities by making wait or abandon decisions dynamically as they wait in the queue. The queueing model takes the customers' abandonment time distribution as an input and studies the resulting virtual waiting time distribution. In equilibrium, the customers' abandonment behavior and the system performance must be consistent across the two models. Therefore, combining the two models and imposing this consistency requirement, we show that there exists a unique equilibrium. Lastly, we provide a computational scheme to calculate the equilibrium numerically. [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]

Endometriosis is a chronic disease mostly affecting women at reproductive age. There is a clear association between endometriosis and infertility; however, exact mechanisms are unknown. Some evidence suggests an adverse effect on oocytes. Endometriosis and its surgical treatment can affect quantitative ovarian reserve as well. In the presence of endometriomas, serum level of anti-Müllerian hormone (AMH) seems a more reliable marker of ovarian reserve than antral follicle count. Women with endometrioma have decreased serum AMH levels as compared with healthy controls. This is further declined after surgical excision, and the decline seems permanent. Bipolar cauterization of the ovary seems to be playing a role on ovarian damage. Extraovarian endometriosis and its surgical treatment can also be associated with decreased ovarian reserve, but there is limited information. Patients with endometriosis should be informed about fertility preservation options, especially in the presence of bilateral endometriomas or prior to surgery. [ABSTRACT FROM AUTHOR]

In the context of assisted reproduction, the term ovarian aging is often used to refer to declining potential of ovaries to produce oocytes in adequate number or quality in response to controlled ovarian stimulation (COS). Different aspects of COS have been modified with the intention to increase the number and quality of oocytes obtained for in vitro fertilization. In the setting of ovarian aging, suppression of the luteinizing hormone (LH) surge with gonadotropin-releasing hormone (GnRH) antagonist or short GnRH agonist protocol and stimulation with a daily gonadotropin dosage of ≤300 IU/day seem to be appropriate first choices, and there is a strong need for well-designed randomized controlled trials investigating effects of addition of LH activity, estradiol priming, transdermal testosterone administration, and growth hormone supplementation. Given the lack of high-quality evidence showing effectiveness of one approach over another, other factors such as duration of stimulation, total gonadotropin consumption and cost of medication, patient friendliness, and possible side effect profiles must be considered in tailoring the COS protocol according to each individual's needs and desires. [ABSTRACT FROM AUTHOR]

Are basal FSH measurements, when elevated within its normal range, useful for assessing overall ovarian response and predicting unexpected poor or suboptimal ovarian response? Retrospective cohort study of ovarian stimulation cycles. A total of 1058 ovarian stimulation cycles (891 first, 167 repeated) were included. Anti-Müllerian hormone (AMH) values were categorized into four (0 to ≤0.6, >0.6 to ≤1.2, >1.2 to ≤3.0, >3.0 to ≤6.25 ng/ml) and basal FSH levels into four groups (<25th percentile: >3.5 to 6.1 IU/ml; 25–75th percentile: >6.1 to ≤8.5 IU/ml; >75–90th percentile: >8.5 to ≤9.9 IU/ml; >90th percentile: >9.9 to ≤12.5 IU/ml). Including only first cycles, a significant independent effect of basal FSH on retrieved cumulus–oocyte complex (COC) count was seen for all basal FSH categories (>90th, >75 to ≤90th, >25 to ≤75th compared with ≤25th percentile, P < 0.001, P = 0.001 and P = 0.007, respectively), when adjusted for age, body mass index (BMI), AMH, antral follicle count (AFC), starting dose and gonadotrophin type. Including only first cycles, patients aged 35 years or older with AFC of 5 or above and AMH 1.2 ng/ml or above, showed significantly higher odds of unexpected poor or suboptimal response if they had higher basal FSH values. Most prominently in the above 90th percentile group (OR 8.64, 95% CI 2.84 to 28.47 compared with <25th percentile) but lower categories (>25th to ≤75th percentile: OR 3.04, 95% CI 1.42 t 6.99; >75th to ≤90th percentile: OR 3.47, 95% CI 1.28 to 9.83 compared with ≤25th percentile) also showed a significant association after adjusting for age, AMH, BMI, AFC, dose, and gonadotrophin type. In patients with a second cycle, an increase in FSH levels in the second round compared with the first was associated with fewer retrieved COCs (estimate: –0.44, 95% CI –0.44 to –0.05, P = 0.027). This effect was adjusted for changes in age, FSH, AFC, starting dose, stimulation duration and change in medication type. Basal FSH is independently associated with overall ovarian response. Moreover, it is associated with unexpected poor or suboptimal response in patients, who would fulfill POSEIDON group 2 criteria after oocyte retrieval. [ABSTRACT FROM AUTHOR]

• The current study represents the first large-scale investigation providing significant data on the feasibility and reliability of the hypo-osmotic swelling test (sperm viability test) on sibling oocytes across different sperm origins (ejaculated/testicular) and processing methods (fresh/frozen-thawed) in the context of assisted reproductive technology. • Hypo-osmotic swelling test is more reliable in fresh samples than in those subjected to the freeze–thaw process. • Hypo-osmotic swelling test is not effective in predicting viability in frozen-thawed specimens, regardless of sperm origin. • Hypo-osmotic swelling is considered a safe method for selecting viable sperm in all subgroups. The viability of sperm is a crucial factor for achieving a successful pregnancy in intracytoplasmic sperm injection (ICSI) cycles. The aim of this study was to evaluate the accuracy of the hypo-osmotic swelling test (HOST) in fresh and frozen-thawed sperm samples of different origins (ejaculated/testicular). A retrospective analysis was conducted on the outcomes of 2167 oocytes subjected to ICSI using motile and immotile-HOST-positive sperm from 2011 to 2023. We evaluated embryonic development, as well as clinical, obstetric, and neonatal outcomes in four groups based on different sperm origins (ejaculated/testicular) and processing (fresh/frozen). When comparing the results of ICSI between motile and immotile-HOST-positive sperm within each group, it was observed that there were no significant differences in the outcomes for fresh samples. However, for frozen-thawed samples, fertilization rates and blastocyst development rates were significantly lower when ICSI was performed with immotile-HOST-positive sperm compared to motile sperm. Of note, clinical, obstetric, and neonatal outcomes were statistically similar across all groups. Our findings indicate that HOST is more reliable in fresh samples than in those subjected to the freeze–thaw process. Nonetheless, HOST is considered a safe method for selecting viable sperm in all subgroups. [ABSTRACT FROM AUTHOR]

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]

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]

The aim of this study was to evaluate the feasibility of intraoperative endoscopic ultrasound guidance for excision of symptomatic deep intramural myomas that are not otherwise visible at laparoscopy. Seventeen patients with symptomatic deep intramural myomas who underwent laparoscopic myomectomy with intraoperative endoscopic ultrasound guidance were followed up and reported. All myomas were removed successfully. The endometrium was breached in one patient. All patients were relieved of their symptoms and three patients presenting with infertility conceived. There were no short- or long-term complications associated with the procedure. One patient who had multiple myomas necessitated intravenous iron treatment prior to discharge. Laparoscopic removal of small symptomatic deep intramural myomas is facilitated by the use of intraoperative endoscopic ultrasound that enables exact localisation and correct placement of the serosal incision. IMPACT STATEMENT • What is already known on this subject: When the myoma is symptomatic, compressing the endometrium, does not show serosal protrusion and is not amenable to hysteroscopic resection, laparoscopic surgery may become challenging. • What do the results of this study add: The use of intraoperative endoscopic ultrasound under these circumstances may facilitate the procedure by accurate identification of the myoma and correct placement of the serosal incision. • What are the implications of these findings for clinical practice and/or further research: Intraoperative ultrasound should be more oftenly used to accurately locate deep intramural myomas to the end of making laparoscopy feasible and possibly decreasing recurrence by facilitating removal of otherwise unidentifiable disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the feasibility of intraoperative endoscopic ultrasound guidance for excision of symptomatic deep intramural myomas that are not otherwise visible at laparoscopy. Seventeen patients with symptomatic deep intramural myomas who underwent laparoscopic myomectomy with intraoperative endoscopic ultrasound guidance were followed up and reported. All myomas were removed successfully. The endometrium was breached in one patient. All patients were relieved of their symptoms and three patients presenting with infertility conceived. There were no short- or long-term complications associated with the procedure. One patient who had multiple myomas necessitated intravenous iron treatment prior to discharge. Laparoscopic removal of small symptomatic deep intramural myomas is facilitated by the use of intraoperative endoscopic ultrasound that enables exact localisation and correct placement of the serosal incision. Impact statement What is already known on this subject: When the myoma is symptomatic, compressing the endometrium, does not show serosal protrusion and is not amenable to hysteroscopic resection, laparoscopic surgery may become challenging. What do the results of this study add: The use of intraoperative endoscopic ultrasound under these circumstances may facilitate the procedure by accurate identification of the myoma and correct placement of the serosal incision. What are the implications of these findings for clinical practice and/or further research: Intraoperative ultrasound should be more oftenly used to accurately locate deep intramural myomas to the end of making laparoscopy feasible and possibly decreasing recurrence by facilitating removal of otherwise unidentifiable disease. [ABSTRACT FROM AUTHOR]

A 30-year-old woman with premature ovarian insufficiency had two follicles measuring 17 mm and 14 mm on day 3 of her menstrual cycle. Serum oestradiol concentration was 210 pg/ml. Recombinant human chorionic gonadotrophin was given and 5 mg/day letrozole started orally. One metaphase II oocyte was collected 36 h later. A 4-cell embryo was vitrified on the second day after fertilization. Letrozole was stopped on cycle day 8 due to absence of any other visible antral follicles. Oestradiol valerate 6 mg/day was started and the endometrium was 9.2 mm on cycle day 11. The embryo was warmed and transferred on cycle day 13, the 8th day after oocyte retrieval. Luteal phase support with progesterone, oestradiol and low molecular weight heparin was started on the day of transfer and continued until the 10th gestational week. A healthy girl weighing 3200 g was born at term. Early follicular phase oocyte collection did not result in early opening of the implantation window. Apparently secretory transformation was not started until luteal phase support, enabling a cleavage stage embryo transferred 8 days later to implant. Either corpus luteum formation could be disrupted or the endometrium could remain unresponsive to progesterone during the early follicular phase. [ABSTRACT FROM AUTHOR]

This retrospective study aims to determine the more predictive ovarian reserve marker when there is discordance between anti-Müllerian hormone (AMH) and antral follicle count (AFC) in patients with diminished ovarian reserve (DOR). Patients who underwent ICSI because of DOR were divided into three groups. Group 1: patients with low AMH (<1.1 ng/ml) and AFC (n < 7), group 2: patients with low AMH (<1.1 ng/ml) and normal AFC (n ≥ 7) and group 3: patients with normal AMH (≥1.1 ng/dl) and low AFC (n < 7). Demographic values, follicle output rate (FORT) score and follicle to oocyte index (FOI) score of the groups were compared. Totally, 662 cycles were enrolled in the study. There were 418 cycles in group 1, 167 cycles in group 2 and 77 cycles in group 3. As the primary result, FORT and FOI scores were higher in group 3 than the other two groups. Median FORT Score with quartiles: group 1: 100 (66–150), group 2: 71 (57–100), group 3: 136 (96–200), p<.01 – median FOI score with quartiles: group 1: 83 (50–140), group 2: 71 (40–100), group 3: 116 (66–216), p<.01. In conclusion, serum AMH level has more predictive value for stimulation success if there is discordance with AFC. What is already known on this subject? Female age, serum Anti-Müllerian Hormone (AMH) levels, and antral follicle count (AFC) are commonly used to assess ovarian reserve and predict response to ovarian stimulation. AMH and AFC are both positively correlated with ovarian reserve. What do the results of this study add? If there is discordance between AFC and AMH in patients with diminished ovarian reserve (DOR), the ovarian response is better in patients with high AMH and low AFC than the patients with low AMH and high AFC. What are the implications of these findings for clinical practice and/or further research? It is important to assess both AFC and AMH before controlled ovarian hyperstimulation, to predict ovarian response in DOR patients, rather than assessing AFC or AMH alone. [ABSTRACT FROM AUTHOR]

Background It is well established that singletons born of assisted reproductive technology are at higher risk of preterm birth and other adverse outcomes. What remains unclear is whether the increased risk is attributable to the effects of the treatment alone or whether the underlying causes of infertility also play a role. The aim of this study was to examine whether any of the six categories of causes of infertility were associated with a direct effect on preterm birth using causal mediation analysis. Methods We assembled a hospital-based cohort of births delivered at a large tertiary care hospital in Montreal, Canada between 2001 and 2007. Causes of infertility were ascertained through a clinical database and medical chart abstraction. We employed marginal structural models ( MSM) to estimate the controlled direct effect of each cause of infertility on preterm birth compared with couples without the cause under examination. Results The final study cohort comprised 18 598 singleton and twin pregnancies, including 1689 in couples with ascertained infertility. MSM results suggested no significant direct effect for any of the six categories of causes. However, power was limited in smaller subgroup analyses, and a possible direct effect for uterine abnormalities (e.g. fibroids and malformations) could not be ruled out. Conclusion In this cohort, most of the increased risk of preterm birth appeared to be explained by maternal characteristics (such as age, body mass index, and education) and by assisted reproduction. If these findings are corroborated, physicians should consider these risks when counselling patients. [ABSTRACT FROM AUTHOR]

The aim of this retrospective cohort study was to compare the effectiveness of the new flexible progestin primed ovarian stimulation (fPPOS) protocol with the flexible gonadotropin-releasing-hormone antagonist (GnRH-ant) protocol in women with decreased ovarian reserve (DOR). Twenty-seven women who underwent fPPOS and 54 age-matched women who received GnRH-ant for pituitary suppression were included in the study. All women had DOR and underwent oocyte cryopreservation. Three-hundred IU/day FSH was started on cycle day 2–3 and 0.25 mg/day GnRH-ant or 10 mg/day medroxyprogesterone acetate was started when the leading follicle reached 14 mm or serum oestradiol level was ≥200 ng/mL. The median duration of stimulation, day of commencing pituitary suppression and duration of suppression were similar in both groups, with 8, 5, and 5 days, respectively. The median number of cumulus-oophorous complexes (4.0 vs 5.5), metaphase-two oocytes (3 vs 4), the total number of oocytes cryopreserved (3.0 vs 4.5), and oocyte maturation rates (0.67 vs 0.70) were similar between the fPPOS and GnRH-ant groups, respectively. There was one case of premature ovulation in the fPPOS group and none in the GnRH-ant group (p = 0.91). In conclusion, fPPOS may be used in women with DOR without compromising the number of oocytes retrieved and seems a viable alternative to the flexible GnRH-ant protocol. [ABSTRACT FROM AUTHOR]

Endometriosis usually presents as cyclical pain in the pelvis but may also present as painful cutaneous lesions. Many diseases may mimic hidradenitis suppurativa (HS) since HS, a chronic inflammatory painful skin disease, is a clinical diagnosis. A 32-year-old woman presented with painful lumps on her vulva and groin accompanied with bloody discharge during menstruation. She was followed up with preliminary diagnosis of endometriosis. Previous excision without definitive diagnosis resulted in temporary relief. She was prescribed oral contraceptive pills that alleviated her symptoms but quitted due to headache. Surgical excision was performed for definitive diagnosis and therapeutic relief. Pathology report revealed HS. She was prescribed oral doxycycline. She responded well to the therapy and has symptom-free for the last 2 years. She delivered one healthy girl via cesarian section 2 years after the treatment. Endometriosis and HS should be included in the differential diagnosis when women present with menstrual painful lesions around external genitalia for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the effect of rescue in vitro maturation and immediate intracytoplasmic sperm injection (ICSI) application on fertilisation success and early embryonic development of metaphase I (MI) oocytes. This was a retrospective cohort study including 2425 sibling oocytes in 259 ICSI cycles. ICSI was performed on 104 GV (germinal vesicle) oocytes which had reached the metaphase II (MII) stage (Group 1) and 231 MI oocytes which had reached the MII stage (Group 2) following IVM (in vitro maturation). Immediate ICSI was applied following oocyte aspiration on 292 MI stage (Group 3) and 1798 MII stage oocytes (Group 4). Normal fertilisation rates in Groups 1, 2, 3 and 4 were 51.9%, 39%, 30.1% and 59.5%, respectively. The rates of blastocyst development per oocyte and per zygote were calculated as 3.8%, 3.0%, 6.8%, 14.1% and 7.4%, 7.7%, 22.7%, 23.6% for Groups 1, 2, 3 and 4, respectively. The blastocyst development rate was significantly higher in the MI-ICSI group compared with other immature oocytes. Even though performing ICSI on the oocytes at the MI stage on the day of oocyte aspiration resulted in lower fertilisation rates, it was associated with significantly higher rates of blastocyst development. [ABSTRACT FROM AUTHOR]

Most proposed definitions of recurrent implantation failure (RIF) are based on clinical judgement, probably affected by patients' demands. They are not based on robust statistical considerations. As a result, a diagnosis of RIF is commonly made too early, exposing couples to the risk of overdiagnosis and overtreatment. However, the situation is changing, and three statistical approaches have recently been proposed. The first is a probability model based on the chances of success per cycle and suggests for the definition three failed oocyte retrieval cycles with all embryos being transferred in women younger than 40 years of age. The second approach suggests an individualized diagnosis that takes into consideration multiple factors, while the third is also based on individualization but mainly relies on anticipated euploidy rates across the female age range. All these approaches have their pros and cons. Regardless of the specific peculiarities, they represent steps in the right direction, with the intent of providing a statistically sound definition. However, these attempts will not be useful unless endorsed by the scientific community in general. There is a pressing need for a rigorous and shared definition of RIF that will be widely accepted by researchers, scientific societies and other stakeholders, including patients. [ABSTRACT FROM AUTHOR]