Variations of the Relative Parasympathetic Tone Assessed by ANI During Oocyte Retrieval Under Local Anaesthesia with Virtual Reality : A Randomized, Controlled, Monocentric, Open Study.

Transvaginal oocyte retrieval is an outpatient procedure performed under local anaesthesia. Hypno-analgesia could be effective in managing comfort during this procedure. This study aimed to assess the effectiveness of a virtual reality headset as an adjunct to local anaesthesia in managing nociception during oocyte retrieval. This was a prospective, randomized single-centre study including patients undergoing oocyte retrieval under local anaesthesia. Patients were randomly assigned to the intervention group (virtual reality headset + local anaesthesia) or the control group (local anaesthesia). The primary outcome was the efficacy on the ANI®, which reflects the relative parasympathetic tone. Secondary outcomes included pain, anxiety, conversion to general anaesthesia rate, procedural duration, patient's and gynaecologist's satisfaction and virtual reality headset tolerance. ANI was significantly lower in the virtual reality group during the whole procedure (mean ANI: 79 95 CI [77; 81] vs 74 95 CI [72; 76]; p < 0.001; effect size Cohen's d -0.53 [-0.83, -0.23]), and during the two most painful moments: infiltration (mean ANI: 81 +/- 11 vs 74 +/- 13; p < 0.001; effect size Cohen's d -0.54[-0.85, -0.24]) and oocytes retrieval (mean ANI: 78 +/- 11 vs 74.40 +/- 11; p = 0.020; effect size Cohen's d -0.37 [-0.67, -0.07]).There was no significant difference in pain measured by VAS. No serious adverse events related were reported. The integration of virtual reality as an hypnotic tool during oocyte retrieval under local anaesthesia in assisted reproductive techniques could improve patient's comfort and experience.

GnRH agonist trigger in poor prognosis patients undergoing a multicycle approach through DuoStim or consecutive stimulations: a SWOT analysis.

PURPOSE OF REVIEW: Identify the most recent and significant evidence regarding the ovulation trigger within the framework of a multicycle approach through DuoStim, providing valuable insights for improving treatment strategies in patients with a poor prognosis. RECENT FINDINGS: The trigger method plays a pivotal role in optimizing in-vitro fertilization (IVF) stimulation, influencing oocyte retrieval and maturation rates, as well as follicle recruitment in consecutive ovarian stimulations such as double stimulation. Decision-making involves multiple factors and, while guidelines exist for conventional stimulation, specific recommendations for the multicycle approach are not well established. SUMMARY: The different methods for inducing oocyte maturation underscore the need for personalization of IVF protocols. The GnRH agonist trigger induces rapid luteolysis and establishes favorable hormonal conditions that do not adversely affect the recruitment of consecutive follicular waves in the context of DuoStim. It serves as a valid alternative to hCG in freeze-all cycles. This strategy might enhance the safety and flexibility of ovarian stimulations with no impact on oocyte competence and IVF efficacy.

Effects of donor age and reproductive history on developmental potential of ovum pickup oocytes in Japanese Black cattle (Wagyu).

The objectives of this study were to analyze the (1) effects of donor age and multiparity on development of in vitro fertilization (IVF) embryos after ovum pickup (OPU), (2) effects of repeated and consecutive OPU-IVF procedures on embryo development, and (3) embryo production from OPU-IVF in donors with differing embryo yields after multiple ovulation and embryo transfer technology (MOET) in Japanese Black cattle (Wagyu). Donors were pre-treated with low-dosage follicle-stimulating hormone (FSH; 200 IU total), and oocytes were collected via OPU and fertilized by IVF to generate blastocysts. The number of oocytes collected per OPU session per donor was lower in heifers (2-4 years old, 5.3 oocytes) than in primiparous and pluriparous cows (2-10 years old, 13.6-19.1 oocytes; P < 0.05). Rates of blastocyst development for oocytes from heifers (33.1%) were lower than for those from cows (2-10 years old, 44.1-54.3%; P < 0.05), and average blastocyst yield/OPU/animal was lower in heifers (3.7) than in 5-6 years old cows (10.1; P < 0.05). Donors undergoing five consecutive OPU-IVF sessions after low-dosage FSH showed similar oocyte retrieval (12.2-15.1 oocytes per OPU/animal), blastocyst development rates (35.6-45.0%), and embryo yield/OPU/animal (4.8-5.8; P > 0.05) across sessions. Additionally, embryo yield from OPU-IVF was significantly improved in animals with previous low embryo yield from MOET (5.9 vs. 2.6, respectively, P < 0.05). These results indicate that Wagyu cows with previous births can be more productive as OPU-IVF donors than heifers, and oocytes from donors undergoing to five consecutive OPU-IVF cycles are competent for embryo development without loss of embryo yield/OPU/animal. Moreover, OPU-IVF can be used for embryo production and breeding from all elite Japanese Black cattle, regardless of previous low embryo yield in routine MOET.

Proximal tubal occlusion first or oocyte retrieval first for patients with hydrosalpinx?

PURPOSE: Our study aimed to investigate the best time to manage hydrosalpinx to improve pregnancy outcomes during in vitro fertilization-embryo transfer (IVF-ET). METHODS: Patients with hydrosalpinx who received IVF treatment were analyzed retrospectively. And two groups were included to compare the effects of different timing treatment of hydrosalpinx on IVF pregnancy outcomes, "Proximal Tubal Occlusion First Group" (Group Ligation-COH) and "Oocyte Retrieval First Group" (Group COH-Ligation). The main outcome measures included: ovarian response indexes, laboratory indexes and clinical pregnancy outcomes. Univariate and multivariate Logistic regression analysis was performed for outcome indicators, and the odds ratios (OR) and 95% confidence interval (CI) were used. RESULTS: A total of 1490 patients were included (n = 976 Ligation-COH and n = 514 COH-Ligation). The Gn starting dose and MII rate in group Ligation-COH were significantly higher than those in group COH-Ligation (203.33 ± 58.20 vs. 203.33 ± 58.20, 81.58% vs. 80.28%, P < 0.05). The number of oocytes obtained and the number of available D3 embryos in group COH-Ligation were higher than those in group Ligation-COH (15.10 ± 7.58 vs. 13.45 ± 6.42, 10.92 ± 5.81 vs. 9.94 ± 5.15, P < 0.05). Although the number of ET cycles per IVF cycle in group COH-Ligation was higher than that in group Ligation-COH (1.88 ± 1.00 vs. 1.48 ± 0.70, P < 0.05), the biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, live birth rate and cumulative live birth rate in group Ligation-COH were significantly higher than those in group COH-Ligation (60.83% vs. 46.27% for biochemical pregnancy, 55.69% vs. 38.5% for clinical pregnancy, 26.18% vs. 17.74% for multiple pregnancy, 47.08% vs. 25.26% for live birth, 69.47% vs. 47.47% for cumulative live birth, P < 0.05), and the miscarriage rate in group Ligation-COH was lower than that in group COH-Ligation (10.47% vs. 17.20 for early abortion, 4.49% vs. 15.86% for late abortion, P < 0.05). In logistic regression analysis, after adjustment for age and multiple factors, the above results were still statistically significant differences (P < 0.001). For elderly patients, the clinical pregnancy rate, multiple birth rate and live birth rate in group Ligation-COH were also higher than those in group COH-Ligation (P < 0.001). No significant differences were detected for patients with diminished ovarian reserve. CONCLUSIONS: For the choice of ligation operation time, we recommend that patients choose tubal ligation first and then ovulation induction and oocyte retrieval treatment.

Contribution of medico-administrative databases to health vigilance: example of post-oocyte retrieval infections.

STUDY QUESTION: Can we monitor post-oocyte retrieval infections in the French national health data system to complement the French ART vigilance system? SUMMARY ANSWER: Medico-administrative databases provide a more comprehensive view of post-oocyte retrieval infections and can be used to detect abnormal increases in frequency and outlier ART centers as a complementary tool to the ART vigilance system. WHAT IS KNOWN ALREADY: The various studies of ART complications are reassuring, showing relatively low overall complication rates. Nonetheless, the European Union has set up a vigilance system to monitor these complications. However, this system is not an exhaustive source of information and does not provide a complete overview of post-ART complications. STUDY DESIGN, SIZE, DURATION: The study population was identified from the comprehensive French national hospital discharge database. It included women under 46 years of age undergoing an oocyte retrieval in 2019, classified into three population subgroups according to the indication of oocyte retrieval: infertility (IF) , fertility preservation (FP), and oocyte donation (OD) . The study population included 52 098 women who had undergone 65 948 oocyte retrievals in 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Hospital stays and delivery of antibiotics within 31 days after oocyte retrieval were analyzed. Women and infections were characterized according to various characteristics (age, comorbidities, indication of oocyte retrieval, type of hospital stay, length of hospital stay, type of antibiotherapy, etc.). Multivariate analysis was performed to determine the relation between the occurrence of infection and women's characteristics, and results are expressed as odds ratios (ORs) and 95% CI. A funnel plot and a box plot were used to compare the infection rate per center with the national average and to detect outliers. MAIN RESULTS AND THE ROLE OF CHANCE: Infections in the month following the oocyte retrieval represented 6.9% of the procedures in 2019 (n = 4522). Of these infections, 112 were hospitalized (0.2% of oocyte retrievals), and 4410 were non-hospitalized (6.7% of oocyte retrievals). The hospitalized infections were essentially gynecological infections (40.9%) and urinary tract infections (23.5%). In 87.9% of non-hospitalized infections, a single antibiotic therapy was prescribed. Mixed-effect model analysis showed that the risk of infection was significantly higher in women under 30 years of age, in the FP population, in supplementary universal health coverage (CMU-C) beneficiaries, and women with endometriosis. Funnel plot and box plot analysis showed that three ART centers have an infection rate significantly higher than the national average. In the three centers that stand out from all the others, the objective is to return to these centers to understand the possible reasons for this observed rate and to implement corrective measures. LIMITATIONS, REASONS FOR CAUTION: Despite all its advantages, the French national health data system presents some limitations, such as the risk of inappropriate coding. Another limitation of this study is that we cannot confirm an attributable relation between the infection and the ART procedure, even if the delay of 31 days after oocyte retrieval is consistent with the occurrence of a post-retrieval complication. In addition, antibiotics may be prescribed as a 'precautionary' measure in certain situations (women with a susceptibility to infection, complicated procedures), or as antibiotic prophylaxis for embryo transfer. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limits in identifying post-ART infections in medico-administrative databases, this approach is a promising way to complement the ART vigilance reporting system. This concept developed for infections will also be generalized to other complications with regular feedback to professionals. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was sought for the study. The study was supported by the Agence de la biomédecine, France. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Predicting the ovarian response: towards a determinant model and implications for practice.

OBJECTIVE: To improve the reliability of prediction models for ovarian response to stimulation in ART. DESIGN: A multicenter retrospective cohort study. SETTING: Twelve reproductive centers. PATIENTS: A total of 25,854 controlled ovarian stimulations between 2005 and 2016, including cycles cancelled for inadequate response, were included. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Precision of the prediction of the number of oocytes at ovarian pickup and of cancellation rate for poor ovarian response. RESULTS: Both AMH and antral follicle count exhibit a non-linear effect on the oocyte yield, with a linear relationship after log-transformation. After adjustment for age, BMI, and center, ovarian response observed in a previous stimulation was found to be the best predictor, followed by AMH and AFC. The zero-inflated binomial negative model showed that predictors of cycle cancellation and number of oocytes at retrieval were different, and assimilating cancellation to zero oocyte greatly reduces the determination of the model. Our model was characterized by the best ever reached determination (R2=0.505 for non-naïve women, 0.313 for all the women) and provided evidence of a very strong difference among centers. The results can be easily converted in the prediction of response levels (poor-medium-good-high). Finally, in case of partial report of the above predictors, we show that the univariate prediction based on the best predictor provides a good approximation. CONCLUSION(S): A substantial improvement of the ovarian response prediction is possible in modelling the possible cancellation decision, followed by the oocyte retrieval itself, according to an appropriate model based on previous stimulation and non-linear effects of AMH and AFC.

Effect of follicular wave synchronization using a progesterone-releasing intravaginal device-based protocol on in vitro embryo production in Bos taurus cows subjected to 14-day intervals ovum pick-up.

Follicular wave synchronization (FWS) before ovum pick-up (OPU) is one of the strategies used to improve the efficiency of in vitro embryo production (IVP). This study aimed to evaluate the effect of FWS on the total follicular number, cumulus-oocyte complex (COC) recovery, and in vitro embryo development in Angus cows (n = 33) subjected to OPU with 14-day intersession intervals. Additionally, it was also evaluated the presence of carryover effects given the short intersession interval used. The experiment was run as a 2-treatment (FWS vs. Control) x 2-period (1 vs. 2) crossover design. Animals in the FWS group received an intravaginal progesterone implant (1gr), estradiol benzoate (2 mg), and D-cloprostenol (150 µg) on day 0 and the OPU was performed on day 5. Control group animals did not receive any hormone treatment. The FWS increased the number of 6-10 mm follicles (P = 0.05), but it decreased the COC recovery rate (P < 0.01). The FWS did not affect the total or frozen embryo numbers (P = 0.49 and P = 0.17; respectively), but it increased the total blastocyst cell number (P < 0.01). A carryover effect was found on the total and < 6 mm follicles number (P = 0.10 and P < 0.01; respectively), and on the regular, atretic, viable, and total number of COC (P = 0.01, P = 0.08, P = 0.02 and P < 0.01; respectively). We concluded that the FWS increased the quality of embryos after OPU with 14-day intersession intervals in Angus cows and that this kind of OPU/IVP scheme enabled the existence of a carryover effect, especially on the follicle number and COC morphology.

Haemoperitoneum due to ovarian rupture after oocyte retrieval procedure.

Transvaginal ultrasound-guided oocyte retrieval is the gold-standard technique for oocyte retrieval that has few associated procedural and post-procedural complications. Rarely, severe complications can occur including haemoperitoneum, for which the incidence reported in the literature is approximately 0.08-0.22%. In this report, we present the case of a nulliparous woman in her late 30s who presented to the hospital with severe abdominal pain following transvaginal ultrasound-guided oocyte retrieval and was found to have extensive haemoperitoneum attributed to ovarian rupture.

Exploring the efficacy and beneficial population of preimplantation genetic testing for aneuploidy start from the oocyte retrieval cycle: a real-world study.

BACKGROUND: Preimplantation genetic testing for aneuploidy (PGT-A) is widely used as an embryo selection technique in in vitro fertilization (IVF), but its effectiveness and potential beneficiary populations are unclear. METHODS: This retrospective cohort study included patients who underwent their first oocyte retrieval cycles at CITIC-Xiangya between January 2016 and November 2019, and the associated fresh and thawed embryo transfer cycles up to November 30, 2020. PGT-A (PGT-A group) and intracytoplasmic sperm injection (ICSI)/IVF (non-PGT-A group) cycles were included. The numbers of oocytes and embryos obtained were unrestricted. In total, 60,580 patients were enrolled, and baseline data were matched between groups using 1:3 propensity score matching. Sensitivity analyses, including propensity score stratification and traditional multivariate logistic regression, were performed on the original unmatched cohort to check the robustness of the overall results. Analyses were stratified by age, body mass index, ovarian reserve/responsiveness, and potential indications to explore benefits in subgroups. The primary outcome was cumulative live birth rate (CLBR). The other outcomes included live birth rate (LBR), pregnancy loss rate, clinical pregnancy rate, pregnancy complications, low birth weight rate, and neonatal malformation rate. RESULTS: In total, 4195 PGT-A users were matched with 10,140 non-PGT-A users. A significant reduction in CLBR was observed in women using PGT-A (27.5% vs. 31.1%; odds ratio (OR) = 0.84, 95% confidence interval (CI) 0.78-0.91; P < 0.001). However, women using PGT-A had higher first-transfer pregnancy (63.9% vs. 46.9%; OR = 2.01, 95% CI 1.81-2.23; P < 0.001) and LBR (52.6% vs. 34.2%, OR = 2.13, 95% CI 1.92-2.36; P < 0.001) rates and lower rates of early miscarriage (12.8% vs. 20.2%; OR = 0.58, 95% CI 0.48-0.70; P < 0.001), preterm birth (8.6% vs 17.3%; P < 0.001), and low birth weight (4.9% vs. 19.3%; P < 0.001). Moreover, subgroup analyses revealed that women aged ≥ 38 years, diagnosed with recurrent pregnancy loss or intrauterine adhesions benefited from PGT-A, with a significant increase in first-transfer LBR without a decrease in CLBR. CONCLUSION: PGT-A does not increase and decrease CLBR per oocyte retrieval cycle; nonetheless, it is effective in infertile populations with specific indications. PGT-A reduces complications associated with multiple gestations.

Cumulative live birth rate in mild versus conventional stimulation in progestin-primed ovarian stimulation protocols for individuals with low prognosis.

Objective: The purpose of this study was to evaluate the cumulative live birth rate (CLBR) of mild stimulation and conventional stimulation for the low-prognosis population undergoing PPOS protocols. Methods: This was a retrospective cohort study. We included women with a low prognosis. All women underwent PPOS protocols, and the starting gonadotropin (Gn) dose was 150 IU or 300 IU. The primary outcome measure was CLBR. The secondary outcome measures were the number of oocytes retrieved, number of 2PN oocytes and number of available embryos. Results: In total, 171 women with mild stimulation and 1810 women with conventional stimulation met the criteria. In the PSM model, 171 mild stimulation cycles were matched with 513 conventional stimulation cycles. The gonadotropin dosage in the mild stimulation group was significantly lower than that in the conventional stimulation group (1878.6 ± 1065.7 vs. 2854.7 ± 821.0, P<0.001). The numbers of oocytes retrieved, 2PN oocytes, available embryos and high-quality embryos were also higher in the conventional stimulation group than in the mild stimulation group (P<0.05). There was no significant between-group difference in the cumulative clinical pregnancy rate (26.3% vs. 27.5%, P=0.77). The CLBR after mild stimulation was similar to that after conventional stimulation (21.1% vs. 22.0%, P=0.79). Conclusion: In our study, we found that the CLBRs of mild stimulation and conventional stimulation were similar, despite conventional stimulation resulting in significantly more oocytes and embryos. Thus, mild stimulation can be considered an option for women with a low prognosis in PPOS protocols.

Random start ovarian stimulation before gonadotoxic therapies in women with cancer: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to quantify the effect of random start ovarian stimulation (RSOS) compared with conventional start ovarian stimulation (CSOS) in cancer patients before gonadotoxic treatment. The final analytical cohort encompassed 688 RSOS and 1076 CSOS cycles of cancer patients before gonadotoxic treatment. Eleven studies were identified by database searches of MEDLINE, Cochrane Library and cited references. The primary outcomes of interest were the number of oocytes and mature oocytes collected, the number of embryos cryopreserved and the metaphase II (MII)-antral follicle count (AFC) ratio. The studies were rated from medium to high quality (from 6 to 9) according to the Newcastle-Ottawa Quality Assessment Scale. The two protocols resulted in similar numbers of oocytes collected, MII oocytes, embryos available for cryopreservation and comparable MII-AFC and fertilization rates. The duration of ovarian stimulation was longer (standardized mean difference [SMD] 0.35, 95% CI 0.09 to 0.61; P = 0.009) and gonadotrophin consumption was higher (SMD 0.23, 95% CI 0.06 to 0.40; P = 0.009) in RSOS compared with CSOS. This systematic review and meta-analysis show that the duration of stimulation is longer, and the total gonadotrophin consumption is higher in cancer patients undergoing RSOS compared with those undergoing CSOS, with no significant effect on mature oocyte yield.

Follicular flushing increases the number of oocytes retrieved: a randomized controlled trial.

STUDY QUESTION: Does follicular flushing increase the number of cumulus-oocyte complexes (COCs) retrieved compared to single aspiration? SUMMARY ANSWER: Follicular flushing significantly increases the number of COCs retrieved compared to single aspiration. WHAT IS KNOWN ALREADY: On the basis of published meta-analyses, follicular flushing does not seem to increase the number of oocytes retrieved, the probability of clinical pregnancy, or that of live birth and has been associated with an increase in the duration of oocyte retrieval. It should be noted, however, that all the eligible randomized controlled trials (RCTs) in these meta-analyses have randomized patients into either single aspiration or follicular flushing. This study design might not allow the detection of the true effect of follicular flushing. Despite randomization, this might still be obscured, to an extent, by heterogeneity in patients, stimulation characteristics, and differences in the oocyte retrieval procedure. STUDY DESIGN, SIZE, DURATION: A prospective, single centre, RCT, including 105 patients was performed between July and December 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible patients were those undergoing oocyte retrieval for ICSI, aged <43 years, with BMI 18-35 kg/m2. Patients with all types of ovarian response (low-normal-high), as assessed on the day of triggering final oocyte maturation, were included. Random allocation of the ovaries of each patient to either single aspiration or follicular flushing was performed on the day of oocyte retrieval, using a computer-generated randomization list. Patients could enter the study only once. All follicles from ovaries allocated to either follicular flushing or single aspiration, were aspirated by the same 16G double lumen needle, with a constant aspiration pressure of 190 mmHg, resulting in flow rate of 0.42 ml/s. In the ovaries allocated to the follicular flushing group, if a COC was not recovered in the initial aspirate of each follicle, follicular flushing was performed until a COC was retrieved, up to a maximum of five times. The primary outcome measure was the number of COCs retrieved. Secondary outcomes were oocyte recovery rate, oocyte maturation rate, fertilization rate, and rate of good quality embryos on Day 2. Values are expressed as a median (inter-quartile range). MAIN RESULTS AND THE ROLE OF CHANCE: Significantly more COCs were retrieved in the follicular flushing as compared to the single aspiration group in all patients [5 (7) vs 2 (3), P < 0.001, respectively], as well as in patients with high [9 (3) vs 5 (4), P < 0.001, respectively], normal [5 (2) vs 2 (3), P < 0.001, respectively] and low [1 (1) vs 1 (1), P < 0.001, respectively] ovarian response. In patients with low ovarian response, no COCs were retrieved in 5.7% of the ovaries in the flushing group vs 42.8% of the ovaries in the single aspiration group (P < 0.001). The oocyte retrieval rate was significantly higher in the follicular flushing vs the single aspiration group, in all patients [88.9% (25.0) vs 45.5% (37.5), P < 0.001, respectively], as well as in patients with high [81.8% (15.9) vs 45.5% (22.2), P < 0.001, respectively], normal [85.7% (28.6) vs 40.0% (30.0), P < 0.001, respectively], and low [100% (0) vs 50.0% (100), P < 0.001, respectively] ovarian response. No significant difference was observed regarding maturation rate [85.2% (30.8) vs 100% (33.3), P = 0.78], fertilization rate [76.4% (50) vs 83.3% (50) P = 0.42], and the proportion of good quality embryos on Day 2 [83.3% (40) vs 100% (50), P = 0.62]. Similarly, no differences in the above variables were observed in patients with different types of ovarian response. Follicular flushing as compared to single aspiration was associated with a significant increase in the duration of oocyte retrieval in all patients [248 s (332) vs 135 s (164), respectively], as well as in patients with high [464 s (225) vs 237 s (89), P < 0.001, respectively], normal [248 s (108) vs 141 s (95), P < 0.001, respectively], and low [64 s (59) vs 48 s (10), P < 0.001, respectively] ovarian response. LIMITATIONS, REASONS FOR CAUTION: Although the current study design allows for a more accurate evaluation of the true effect of follicular flushing on the number of COCs retrieved, it does not permit the evaluation of its role on the probability of pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: This is the first RCT to suggest that follicular flushing increases the number of COCs retrieved compared to single aspiration, independently of ovarian response. This implies that follicular flushing plays an important role in the optimization of oocyte retrieval. These results, however, need to be confirmed in future studies, in which an equal flow rate should be used during oocyte retrieval. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT05473455. TRIAL REGISTRATION DATE: 15 July 2022. DATE OF FIRST PATIENT'S ENROLMENT: 27 July 2022.

Influence of the starting day of luteal phase stimulation on double stimulation cycles.

Background: Double ovarian stimulation is one of the most used strategies in poor-prognosis patients. There is a high heterogeneity between the studies regarding the execution of this stimulation protocol. The aim of this study was to investigate whether the day on which luteal phase stimulation begins after the first oocyte retrieval affects ovarian response in DuoStim cycles. Methods: This observational and retrospective study included 541 DuoStim cycles between January 2018 and December 2021 in a private fertility clinic. Patients were assigned to 4 groups according to the timing of the onset of luteal phase stimulation after oocyte retrieval (0-2nd day, 3rd day, 4th day and 5th-6th day). The primary outcome was the number of oocytes retrieved in the luteal phase in each group. Results: No differences were found between groups in the number of oocytes collected (5.12 ± 3.56 vs. 5.39 ± 3.74 vs. 5.61 ± 3.94 vs. 5.89 ± 3.92; p=0,6), MII or number of follicles. An increase in the duration of stimulation was found when stimulation started on the 4th day (10.42 ± 2.31 vs. 10.68 ± 2.37 vs. 11.27 ± 2.40 vs. 10.65 ± 2.37 days, p=0,033). A lower number of fertilized oocytes was observed when stimulation began before the fourth day (3.36 ± 2.80 vs. 3.95 ± 2.53 vs. 4.03 ± 2.73 vs. 4.48 ± 3.11; p=0,036). The number of blastocysts was higher when the stimulation started 5-6 days after retrieval (1.82 ± 1.74 vs. 2.13 ± 1.61 vs. 2.33 ± 2.06 vs. 2.91 ± 2.39; p= 0,030). Discussion: The number of oocytes retrieved does not differ depending on the day that stimulation begins. However, oocytes competence in terms of fertilized oocytes and blastulation, appears to be lower when the second stimulation starts before the fourth day after oocyte retrieval.

Follicular steroidogenesis in random start protocols for oocyte cryopreservation.

PURPOSE: Random start protocols are commonly used for oocyte cryopreservation in women with cancer. However, albeit generally reassuring, available evidence is still insufficient to rule out a sub-optimal cycle outcome. This study aimed to compare follicular steroidogenesis between women initiating the random start protocol in the luteal phase and those initiating in the follicular phase. METHODS: Consecutive women with cancer scheduled for oocyte cryostorage were prospectively recruited. We excluded those requiring a concomitant letrozole assumption. All women received a standardized protocol with recombinant FSH and GnRH antagonists. At the time of oocyte retrieval, follicular fluids were pooled, and a sample was collected and frozen at -80 °C. All samples were assayed concomitantly after thawing by liquid chromatography-tandem mass spectrometry. The concentration of 15 different steroid hormones was determined. RESULTS: Seventy-one women were recruited. Thirty-three initiated the ovarian stimulation in the luteal phase, while the remaining 38 initiated in the follicular phase. Baseline characteristics were generally similar. Cycle outcome did also not differ; the median (interquartile range) number of frozen mature oocytes was 9 (5-14) and 10 (5-21), respectively (p = 0.42). None of the 15 tested steroid hormones differed. CONCLUSIONS: The endocrine microenvironment surrounding oocytes is not markedly influenced by the phase of the menstrual cycle at the initiation of ovarian stimulation. This result further supports the validity of random start protocols.

Risk factors for low oocyte retrieval in patients with polycystic ovarian syndrome undergoing in vitro fertilization.

BACKGROUND: The number of oocytes retrieved does not always coincide with the number of follicles aspirated in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Patients with high expectation of retrieval sometimes obtain few oocytes, which may be induced by improper operation or therapeutic factors. The purpose of this study was to evaluate the distribution data of oocyte retrieval rate (ORR) and to explore the risk factors for low ORR in patients with polycystic ovary syndrome (PCOS) undergoing IVF/ICSI. METHODS: A total of 2478 patients with PCOS undergoing IVF/ICSI were involved in this retrospective case-control study from March 2016 to October 2021. The oocyte retrieval rate was calculated as the ratio of the number of obtained oocytes to the number of follicles (≥ 12 mm) on the trigger day. Patients were divided into a low ORR and a normal ORR group with the boundary of one standard deviation from the mean value of ORR. The patient characteristics, treatment protocols, serum hormone levels, and embryonic and pregnancy outcomes were analyzed. RESULTS: The ORR exhibited a non-normal distribution, with a median of 0.818. The incidence of complete empty follicle syndrome was 0.12% (3/2478). The proportion of patients in the low ORR group who received the progestin-primed protocol was significantly higher than that in the normal ORR group (30.30% vs. 17.69%). A logistic regression analysis showed that the serum estradiol level/follicle (≥ 12 mm) ratio (OR: 0.600 (0.545-0.661)) and progesterone level (OR: 0.783 (0.720-0.853)) on the trigger day were significant factors in the development of a low ORR, with optimal cutoff values of 172.85 pg/ml and 0.83 ng/ml, respectively, as determined by receiver operating curve. Fewer high-quality embryos (2 vs. 5) and more cycles with no available embryos (5.42% vs. 0.43%) were found in the low ORR group. CONCLUSIONS: For patients with PCOS, low estradiol levels/follicles (≥ 12 mm) and progesterone levels on the trigger day and the use of the progestin-primed protocol could be risk factors for low ORR, which leads to a limited number of embryos and more cycle cancellations.

The time interval between oocyte retrieval and frozen embryo transfer does not impact reproductive outcomes.

RESEARCH QUESTION: Does the time interval between oocyte retrieval and frozen embryo transfer (FET) affect pregnancy outcomes after a freeze-all strategy? DESIGN: Retrospective study including a total of 5995 patients who underwent their first FET following a freeze-all cycle between 1 January 2017 and 31 December 2020. Patients were divided into immediate (the interval between oocyte retrieval and the day of first FET ≤40 days), delayed (>40 days but ≤180 days) and overdue groups (>180 days). Pregnancy and neonatal outcomes were analysed, and multivariable regression analysis was used to study the effect of FET timing on the live birth rate (LBR) in the entire cohort and the different subgroups. RESULTS: The LBR was significantly lower in the overdue group than in the delayed group (34.9% versus 42.8%, P = 0.002); however, after adjusting for confounding factors, the difference was not statistically significant. The immediate group had a comparable LBR (36.9%) to the other two groups in both the crude and adjusted analyses. Multivariable regression analysis showed no impact of FET timing on LBR in the whole cohort or in the subgroups according to ovarian stimulation protocol, trigger type, insemination method, reason for freezing all, FET protocol or transferred embryo stage. CONCLUSIONS: The time interval between oocyte retrieval and FET does not impact reproductive outcomes. Unnecessary delays in FET should be avoided to shorten the time to live birth.

Optimal timing to retrieve oocytes for fertility preservation in patients with acute myeloid leukemia: two cases of controlled ovarian stimulation using DuoStim with a literature review.

Fertility preservation (FP) for hematological malignancies is difficult because immediate chemotherapy is needed after diagnosis. We report two cases of acute myeloid leukemia (AML) treated with controlled ovarian stimulation (COS) and oocyte cryopreservation using DuoStim after first-line chemotherapy. In Cases 1 and 2, COS and oocyte retrieval (OR) were performed using DuoStim 116 and 51 days after first-line chemotherapy, respectively, and 14 and 6 unfertilized oocytes, respectively, were cryopreserved. Another round of COS and OR was performed using the random-start method 82 days after first-line chemotherapy, and 22 unfertilized oocytes were cryopreserved. DuoStim is useful to maximize OR for patients with a short interval for FP. Many oocytes can be retrieved depending on the timing of recruitment from primary to secondary follicles, although ovarian reserve capacity declines immediately after first-line chemotherapy. Aggressive FP should be performed before allogeneic hematopoietic stem cell transplantation becomes necessary.

Weekday vs. weekend oocyte retrievals: is there a difference?

The purpose of this study was to evaluate whether there is a difference in procedure duration and time spent in the post anaesthesia care unit (PACU) between weekday (WD) and weekend (WE) oocyte retrievals (ORs). This was a retrospective cohort study of patients compared and stratified based on number of oocytes retrieved (1-10, 11-20, and >20). Student's t-test and linear regression models were used to assess the relationship between AMH, BMI, and a number of oocytes retrieved with the duration of procedure and total time spent in the PACU. 664 patients underwent OR of which 578 met inclusion criteria and were analyzed. There were 501 WD OR cases (86%) and 77 (13%) WE ORs. When stratified by number of oocytes retrieved, there was no difference in procedure duration or PACU time between WD vs. WE OR. Longer procedure times were associated with higher BMI (p = 0.04), AMH (p = 0.01) and oocytes retrieved (p < 0.01). Increased PACU times positively correlated with the number of oocytes retrieved (p = 0.04), but not AMH or BMI. While BMI, AMH, and number of oocytes retrieved are associated with longer intra-operative and post-operative recovery times, there is no difference in procedure or recovery time when comparing WD vs. WE procedures.

A Monocentric Randomized Controlled Clinical Trial to Compare Single- and Double-Lumen Needles in Oocyte Retrieval Procedure in Assisted Reproductive Technologies.

The purpose was to determine any difference in outcomes, primarily in terms of number of retrieved oocytes per procedure, between two different needles used for oocytes retrieval procedure in Assisted Reproductive Technologies: the single-lumen needle (SLN) versus the double-lumen needle (DLN) with follicle flushing after aspiration. This randomized controlled trial included oocyte retrieval (OR) cycles for IVF and ICSI performed in 18 to 42-year-old women between March 2019 and January 2021 at a tertiary-care Fertility Center. A total of 200 ORs were randomized, 100 in each group. The mean number of retrieved oocytes was not different between groups (10.2 ± 6.5 for DLNs vs. 10.7 ± 7.0 for SLNs, p = 0.810). No significant differences were observed also in terms of number of retrieved oocytes/punctured follicles (83.0% ± 27.0% vs. 81.0% ± 22.0%, p = 0.916), number of retrieved oocytes/follicles at trigger (78.0% ± 29.0% vs. 78.0% ± 27.0%, p = 0.881), number of mature oocytes (7.6 ± 5.3 vs. 8.0 ± 5.1, p = 0.519), and pregnancy rate (27% vs. 23%, p = 0.514). However, the time required to retrieve each oocyte was longer using the DLN (1.5 ± 1.3 vs. 1.1 ± 0.9 minutes, p = 0.002). The present study confirmed the new perspectives on the sole use of SLNs in terms of saving time, without affecting the number of retrieved oocytes. Trial registration number and date of registration NCT03611907; July 26, 2018.

Serum steroid metabolome on the day of oocyte retrieval in women with polycystic ovarian syndrome and its association with pregnancy outcome of in vitro fertilization.

Steroid hormone level is a crucial factor affecting the outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The purpose of this study was to evaluate serum steroid metabolome on the day of oocyte retrieval in women with polycystic ovarian syndrome (PCOS) and explore whether specific steroids can be potential indicators to improve the prediction of pregnancy outcomes in PCOS patients undergoing IVF/ICSI. In this study, the serum levels of 21 steroids in 89 women with PCOS and 73 control women without PCOS on the day of oocyte retrieval of the first IVF/ICSI treatment cycle were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). All patients subsequently received good-quality embryo transfer, and the correlation between their steroid profiles and pregnancy outcomes of the first embryo transfer (ET) was retrospectively analyzed. We found PCOS patients had aberrant levels of 11 out of 21 steroid hormones compared to control individuals, with androgen steroid hormones being considerably enhanced. Enzyme activity evaluation indicated that PCOS women might have abnormal activity of CYP17A1, CYP21A2, CYP11B2, CYP19A1, HSD3B, HSD11B, and HSD17B. Additionally, the level of 18-hydroxycorticosterone (p = 0.014), corticosterone (p = 0.035), and 17-hydroxypregnenolone (p = 0.005) were markedly higher in live birth group than in non- live birth group for PCOS women following frozen embryo transfer (FET). Multiple logistic regressions indicated that 18-hydrocorticosterone and 17-hydroxypregnenolone were independently associated with live birth outcomes of PCOS women following FET. Receiver operating characteristic (ROC) curve analysis revealed that 0.595 ng/mL for 18-hydrocorticosterone level (AUC: 0.6936, p = 0.014).and 2.829 ng/mL for 17-hydroxypregnenolone level (AUC: 0.7215, p = 0.005) were the best cutoff values to predict live birth outcomes of PCOS. In conclusion, the blood steroid metabolome was closely related to the IVF/ICSI outcomes of PCOS patients. 18-hydroxycorticosterone and 17-hydroxypregnenolone might be potential indicators to predict pregnancy outcomes of PCOS undergoing IVF/ICSI treatment.