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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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

The study explores the factors influencing the implantation success rate of euploid embryos. We primarily aim to understand the relationship between morphokinetics and implantation outcomes, considering potential confounding variables such as maternal age and morphological features of the embryos. Additionally, we intend to elucidate the role of morphological grading in the interplay between morphokinetics and implantation rates in euploid single embryo transfers. The present retrospective study was conducted between January-2016 and January-2023 in a tertiary university hospital's IVF clinic. Forty-four patients who were followed up in time-lapse incubation (Embryoscope, VitroLife) after intracytoplasmic sperm injection (ICSI) procedure were included. All embryos were individually cultured in a time-lapse incubator from ICSI up to the stage of trophectoderm biopsy. Images were recorded with the use of the integrated microscope in every 15 minutes from seven different focal planes. All annotations were made in a prospective fashion by single experienced senior embryologist. A longitudinal dataset containing information on individuals over time was used with a multilevel modeling approach. A linear mixed-effects model was used to analyze the data. The outcome variable (implantation) was modeled as a function of the time intervals, with random effects for the individual. The significance of the fixed effects was tested using a likelihood ratio test. A p-value of less than 0.05 was considered statistically significant. In 44 transferred single euploid embryos, 30 were implanted (68.1%). There was no marked disparity in demographic distributions between the failure or successful implantation groups (for female age, median (IQR) 39.0 (35.5 to 40.0) vs. 39.0 (34.0 to 40.0), p =.751; for male age, median (IQR) 41.5 (38.2 to 43.8) vs. 39.5 (36.0 to 42.8), p=.318; for BMI median (IQR) 23.3 (21.5 to 25.9) vs. 24.7 (23.3 to 28.2), p=.212). Regarding morphological factors, a significant correlation between inner cell mass (ICM) grade and implantation rate was found (p=.001), but it was not observed in trophectoderm grades (p=.103). In the LME (both fixed and random effects were used) model (fixed effects coefficients were the morphokinetic parameters, random effects were the individual embryos, and the outcome was implantation), a significant negative trend was demonstrated between the delay in the last quartile of embryo timeline and implantation. Specifically, a 50% decline in implantation rates was observed in the last quartile with a 9-hour delay (p=.0369, standard error=.3692). However, adding ICM grades to the LME model diminishes the negative trend (p=.99575). The study indicates that morphokinetics may play a role in the success of euploid single embryo transfer procedures, especially within specific temporal windows might impact implantation rates in euploid SET. However, association is diminished when considered with morphological grading of the embryo. [ABSTRACT FROM AUTHOR]

Does subcutaneous progesterone provide similar live birth or ongoing pregnancy rates as vaginal progesterone in frozen embryo transfer (FET) cycles? Retrospective cohort study (n = 214 women), consisting of 107 women who received subcutaneous progesterone for FET in artificial cycles and 107 women receiving vaginal progesterone who were matched for age and treatment cycle rank acted as controls. All embryos were transferred in an artificial cycle with 6 mg per day oral oestradiol valerate starting on the second or third day of the menstrual cycle. Patients underwent transvaginal ultrasound on the 10th day of priming, and subcutaneous progesterone (50 mg/day) or vaginal progesterone (180 mg/day) was started if the endometrium had a trilinear pattern regardless of its thickness. Embryo transfer was carried out on the sixth day of progesterone administration. Oestradiol and progesterone were continued until a negative pregnancy test, 10 days after the transfer, or until the completion of 10th gestational week. Main outcome measures were live birth or ongoing pregnancy rates. Baseline characteristics were similar between the groups. Positive pregnancy test rates (64.5% versus 58.9%; P = 0.40; RR 1.1; 95% CI 0.89 to 1.35), live birth or ongoing pregnancy rates (39.3% versus 35.5%; P = 0.57; RR 1.11; 95% CI 0.78 to 1.56) and miscarriage rates (29% versus 25.5%; P = 0.68; RR 1.08; 95% CI 0.76 to 1.55) were similar in the subcutaneous progesterone and vaginal progesterone groups, respectively. Subcutaneous progesterone seems to be an effective alternative to vaginal progesterone in patients undergoing FET. Randomized controlled trials comparing it with different progesterone preparations, routes and protocols are needed to better define its role. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis of comparative studies investigated whether progestins are as effective as gonadotrophin releasing hormone (GnRH) analogues for pituitary suppression in assisted reproduction. The primary outcome was live birth rate per woman. Secondary outcomes were live birth or ongoing pregnancy per woman and per embryo transfer, ongoing pregnancy, clinical pregnancy, numbers of oocytes and metaphase-two oocytes, duration of stimulation and gonadotrophin consumption. Adverse events included miscarriage, ectopic pregnancy and multiple pregnancy rates. The GRADE system was used to assess the quality of evidence. Seven studies involving a total of 2047 women were included. Three studies compared a progestin with a GnRH antagonist and four studies compared a progestin with a GnRH agonist. Most studies are non-randomized and report outcomes per embryo transfer, rather than per woman. Although progestins were similar to GnRH antagonists in effectiveness and safety parameters, they were associated with significantly higher live birth or ongoing pregnancy per embryo transfer compared with the short GnRH agonist protocol (RR 1.49, 95% CI 1.16 to 1.91). Progestin primed stimulation lasted significantly longer (mean difference 0.61 days, 95% CI 0.33 to 0.89) and required significantly more gonadotrophins (mean difference 433.2 IU, 95% CI 311.11 to 555.19) than the short GnRH agonist protocol, but the differences were clinically negligible. Safety parameters were similar between progestins and GnRH agonists. In conclusion, progestins can effectively prevent premature ovulation in assisted reproductive technology cycles. If larger and well-designed studies confirm these findings, progestins may be an effective and low-cost alternative to GnRH analogues when a fresh embryo transfer is not planned owing to a medical indication. [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]

A receptive endometrium is required for successful embryo implantation. Endometrial thickness, as measured by ultrasonography, is the most commonly used marker of endometrial receptivity in assisted reproductive technology cycles. Several factors simultaneously affect both endometrial thickness and probability of live birth, including age, oestradiol concentration and oocyte number, among others. Most of the studies investigating a relationship between endometrial thickness and embryo transfer outcomes are retrospective and do not adequately address confounding factors, in addition to other limitations. Despite multiple meta-analyses and studies with large numbers of cycles, controversy still exists. The difference between the results from prospective and retrospective studies is also striking. This article presents a critical appraisal of the studies on endometrial thickness and embryo transfer outcomes in order to highlight methodological issues and how they can be overcome in future studies. Currently available evidence does not seem to support a modification of management just because endometrial thickness is below an arbitrary threshold. [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]

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]

Whether endometriomas grow because of supraphysiological oestradiol levels attained during ovarian stimulation for assisted reproduction techniques is a concern. In this prospective study, 25 women with 28 endometriomas underwent three-dimensional ultrasound using sono-automated volume calculation software. Endometrioma volume was measured on the first day of gonadotrophin injection (V1) and the day of ovulation trigger (V2). Nine (36%) women were stimulated in a gonadotrophin releasing hormone antagonist protocol (GnRH), 13 (52%) in a long, and three (12%) in an ultra-long GnRH agonist protocol. Mean duration of stimulation was 10.3 days with median total gonadotrophin dose of 4500 IU/day. Median number of cumulus oocyte complexes was five, and metaphase-two oocytes was four. None of the endometriomas were punctured during oocyte retrieval. Median V1 was 22.2 ml (12–30 ml) and median V2 was 24.99 ml (11.2–37.4 ml) with P = 0.001. Twenty-three out of 28 endometriomas (82%) grew to some extent during ovarian stimulation. Endometrioma growth was positively correlated with prestimulation cyst volume (Correlation coefficient 0.664; P < 0.01). Although the 3-ml average growth was statistically significant, it could be regarded as clinically insignificant. [ABSTRACT FROM AUTHOR]

Despite their wide and global use, possible short and long-term effects of fertility treatments on children is not well-established. In this review, birth defects and perinatal complications and their relationship with assisted reproductive technology (ART), along with long-term effects of ART on cardiovascular system, metabolism, behavior, cognitive skills, and childhood cancers are discussed. Children conceived through ART are at increased risk for birth defects and perinatal complications such as preterm delivery, low birth weight and small for gestational age. Parental characteristics, underlying infertility etiology and ART procedures themselves may contribute to this. The long-term effects of ART are difficult to establish. Studies so far report that ART children have normal social, emotional, cognitive, and motor functions. Likewise, despite some minor inconsistencies in some studies, they do not seem to be at increased risk for childhood cancers. However, there are a number of studies that imply vascular system may be adversely affected by ART and its possible consequences should be further investigated with follow up studies. Large scale studies with long-term follow up periods are required to determine the effects of ART on conceived children. [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]

Objective: To compare two commonly used protocols (fresh vs. vitrified) used to transfer euploid blastocysts after IVF with preimplantation genetic screening.Design: Randomized controlled trial.Setting: Private assisted reproduction center.Patient(s): A total of 179 patients undergoing IVF treatment using preimplantation genetic screening.Intervention(s): Patients were randomized at the time of hCG administration to either a freeze-all cycle or a fresh day 6 ET during the stimulated cycle.Main Outcome Measure(s): Implantation rates (sac/embryo transferred), ongoing pregnancy rates (PRs) (beyond 8 weeks), and live birth rate per ET in the primary transfer cycle.Result(s): Implantation rate per embryo transferred showed an improvement in the frozen group compared with the fresh group, but not significantly (75% vs. 67%). The ongoing PR (80% vs. 61%) and live birth rates (77% vs. 59%) were significantly higher in the frozen group compared with the fresh group.Conclusion(s): Either treatment protocol investigated in the present study can be a reasonable option for patients. Freezing all embryos allows for inclusion of all blastocysts in the cohort of embryos available for transfer, which also results in a higher proportion of patients reaching ET. These findings suggest a trend toward favoring the freeze-all option as a preferred transfer strategy when using known euploid embryos.Clinical Trial Registration Number: NCT02000349. [ABSTRACT FROM AUTHOR]