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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]

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

The aim of this retrospective study was to compare the oocyte yield with the luteal estradiol patch (LPA) - GnRH antagonist and microdose (MD) flare-up protocols in anticipated poor responders. Fifty-seven women who underwent IVF treatment following stimulation with LPA or MD protocols at McGill Reproductive Centre were matched for age and markers of ovarian reserve. Numbers of oocytes collected (6 vs 7), mature oocytes collected (5 vs 5), and oocyte maturation rates (72%% vs 74%%) were similar. The numbers of good quality embryos available (2 vs 1) and embryos transferred (3 vs 3) were likewise similar. Embryo implantation rate of 16.7%% and clinical pregnancy rate of 38.9%% achieved in the LPA group were almost 50%% higher than the corresponding figures at 10.3%% and 22.2%% in the MD group; however, the differences were not statistically significant ( p > 0.05 for all comparisons). Although the results do not suggest an increased oocyte yield or follicular synchronization with the LPA protocol, the observed trend toward higher embryo implantation and clinical pregnancy rates requires further research. [ABSTRACT FROM AUTHOR]

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

The aim of this retrospective study was to compare the incidence of chromosomal abnormality in embryos from in-vitro maturation (IVM) and IVF cycles. The copy numbers of chromosomes 13, 15, 16, 18, 21,22, X and Y were assessed with fluorescence in-situ hybridization (FISH) in single blastomeres biopsied from cleavage stage embryos. Spare embryos that were not transferred or cryopreserved were also analysed in full. IVM and IVF groups comprised six and 30 couples, with mean ± SD embryos with FISH result of 8.0 ± 4.4 and 11.7 ± 3.8, respectively. The incidence of chromosomal abnormality per FISH result was similar in IVM and IVF embryos (58.7% versus 57.4%, respectively). When embryos were categorized based on maturation time of oocytes in IVM cycles, embryos derived from oocytes that matured 48 h after collection had a higher chromosomal abnormality rate compared with embryos derived from in-vivo matured oocytes and to embryos derived from oocytes that matured in the first 24 h after collection. [ABSTRACT FROM AUTHOR]

Controlled ovarian stimulation with exogenous gonadotrophins and gonadotrophin-releasing hormone (GnRH) analogues enables the collection of multiple oocytes and subsequent development of multiple embryos. However, interfering with the natural hormonal milieu may decrease the probability of successful embryo implantation due to effects on oocytes and/or endometrium. In order to provide a fair comparison of embryo implantation rates between natural cycles and stimulated cycles, bias caused by the presence of multiple embryos available for transfer in stimulated cycles should be avoided. This retrospective study analysed embryo implantation rates in cycles in which only a single embryo was available for transfer in 304 women who had poorly responded to ovarian stimulation in the previous cycle. Embryo implantation rates with different stimulation protocols were as follows: natural cycle, 20% (6/30); gonadotrophin only. 5.6% (3/54); long GnRH protocol. 3.8% (2/52); co-flare protocol. 1.9% (1/52); microdose flare-up. 15.4% (4/26); GnRH antagonists. 14.4% (13/90). Although the difference was not statistically significant there was a trend towards higher implantation rates with natural cycles in this group of women. Natural cycle IVF may be a reasonable and patient-friendly treatment choice yielding an acceptable outcome for women who are known or anticipated poor responders to ovarian stimulation. [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]

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

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

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]

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

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

Objective: In vitro maturation (IVM) of human oocytes can be an alternative treatment option to conventional in vitro fertilization. Women with polycystic ovary syndrome (PCOS) are considered the classical candidates for IVM because of the associated ovarian morphology and because IVM diminishes the risk of developing ovarian hyperstimulation syndrome. The objective of this study was to identify predictive factors for live birth in a cohort of women with PCOS who underwent IVM.Methods: This retrospective study included 159 patients with PCOS who had IVM cycles in which single or double embryo transfer was performed. The IVM protocol included three days of gonadotropin ovarian stimulation and hCG priming when the leading follicle size was 10-12 mm. Collected cumulus-oocyte complexes were cultured for 24 h for maturation. Intracytoplasmic sperm injection (ICSI) was used for fertilization. Embryo transfer was performed two days after fertilization. Demographic and clinical parameters were analyzed with logistic regression to identify predictors for live birth.Results: The women's mean age was 27.4 years, the mean number of retrieved oocytes was 14, and the live birth rate was 34.6%. The logistic regression revealed the following significant factors for live birth: infertility duration (OR 0.9; 95% CI, 0.82-0.98), number of collected oocytes (OR 1.56; 95% CI, 1.01-3.2), embryo cell number (OR 2.1; 95% CI, 1.4-3.5), and embryo grade (OR 1.84; 95% CI, 1.13-4.2).Conclusion: Infertility duration, oocyte number, embryo cell number, and embryo grade were the most significant predictors for live birth after IVM in PCOS patients. These prognostic factors can be used when planning treatment or counselling patients. [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]