Total Number Of Oocytes Research Articles

Evaluation of intra-ovarian platelet-rich plasma administration on oocytes-dependent variables in patients with poor ovarian response: A retrospective study according to the POSEIDON criteria

BackgroundPoor ovarian response (POR) is among the common findings in infertile women with no significant underlying condition. The aim of this study was to investigate the intra-ovarian potential of platelet-rich plasma (PRP) administration on oocytes-dependent variables in the POR women grouped according to the POSEIDON criteria.MethodsThis retrospective study was performed on POR women with no underlying condition who have undergone intra-ovarian PRP injection. As well as patients’ age, the number of total and MI, MII, and GV oocytes were extracted from the files. The laboratory variables including anti-mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were also gathered. In order to reduce any bias due to the possible differences in kits or devices, a single laboratory with the highest number of cases was selected and others were excluded from the study. Then, the included cases were grouped into four according to the POSEIDON criteria and analyzed for the mentioned variables by SPSS, version 25. The statistical significance level was set as P-value < 0.05.ResultsFrom 383 cases, a total number of 96 women were enrolled in this study. According to the POSEIDON criteria, group 4 (Age ≥ 35 years, AMH < 1.2 ng/mL) with the ratio of 56/96 (58.3%) had the highest prevalence among others. As the analyses showed, changes in the laboratory variables (LH, FSH, AMH, and estradiol) were not significant in almost all the groups following the intervention. Regarding the total oocytes number, PRP administration caused a significant increase in the total number in all the groups (all P < 0.05). Also, the number of MII oocytes was significantly increased following the treatment in all groups except for group 2 (Age ≥ 35 years, AMH ≥ 1.2 ng/mL; all P < 0.05). Of 96 cases, 14 (14.6%) got clinically pregnant following assisted reproductive techniques which this number were significantly differed among the groups (P = 0.002).ConclusionThis study showed that PRP treatment was effective on total and MII oocyte numbers in the patients with POR, however, further studies are required.

Defective oogenesis in mice with pristane-induced model of systemic lupus

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by generation of autoantibodies and severe damage of various organs.The hormonal changes associated with pregnancy and especially estrogen might lead to damage of reproductive function and ovarian quality.We employed a pristane-induced lupus model of Balb/c mice which resembles human lupus in an attempt to follow oogenesis disruption during the disease progression. The integrity of cytoskeletal and chromatin structures was estimated in oocytes derived by hormonally stimulated ovulation in lupus mice and the results were compared with those from healthy mice.Chromatin, tubulin and actin structures in oocytes were detected by Hoechst 33258, anti-alpha-tubulin antibody and rhodamine-labeled phalloidin, respectively. All available meiotic spindles were analyzed – in immature (metaphase I) and mature oocytes (metaphase II).The total number of mature oocytes obtained from lupus mice was lower compared to healthy controls. The maturation rate was 9.8 % for lupus mice, 12.7 % for 7-month old controls, and 14.3 % for the young control mice (4 weeks old). Another major difference between the studied groups was the higher percentage of defective metaphase I spindles registered in oocytes derived from lupus mice (60 % normal spindles), while for the young and older controls this proportion was 86 % and 81 %, respectively. No such difference was registered for metaphase II spindles. For both metaphase I and metaphase II oocytes, the proportions of normal actin cap and chromosomal condensation were similar between the experimental groups.

TWO IS NOT ALWAYS GREATER THAN ONE: PATIENTS (PTS) WITH ONE OVARY (1O) HAVE SIMILAR ASSISTED REPRODUCTIVE TECHNOLOGY (ART) OUTCOMES COMPARED TO PTS WITH TWO OVARIES (2O)

Current data conflicts on ART outcomes in pts with 1O. Furthermore, data is limited evaluating embryo quality in these pts. We assessed number of mature oocytes (M2s) and total oocytes retrieved, embryo quality, and embryo transfer outcomes in pts with 1O compared to 2O. We performed a retrospective cohort study of all pts with 1O who underwent ART at one academic institution from 2012-2020. Pts were 3-to-1 matched to 2O controls by age, ART cycle type (oocyte freezing vs. embryo banking/in vitro fertilization) and number of ART cycles. Our primary outcome was number of M2s. Secondary outcomes included AMH and day 2 FSH prior to first cycle, number of retrieved oocytes, %M2s, 2PN fertilization rate, blastocyst formation rate (BFR), number of euploid embryos, euploidy rate, clinical pregnancy rate per pt (CPR), and live birth rate per pt (LBR). Subgroup analyses were performed comparing left vs. right ovary in situ and reason for loss of 1O. Mann-Whitney, Kruskal-Wallis, Fisher’s exact, and Wilcoxon signed-rank tests were used for statistics; with p<0.05 considered significant. 104 pts (158 cycles) with 1O were matched to 312 pts (474 cycles) with 2O. Reasons for loss of 1O were torsion (18%), benign cyst (30%), malignant tumor (46%), and congenital absence (6%). Median pt age was 35.5y vs. 35.0y in pts with 1O vs. 2O (p=0.9). AMH was lower (median 1.1 vs 2.2, p<0.01) and day 2 FSH was higher (median 7.4 vs 6.2, p<0.01) in pts with 1O. See Table 1 for outcomes. Pts with 1O had fewer M2s and oocytes retrieved than pts with 2O; however, pts with 1O had more than half the number of M2s and oocytes retrieved than in pts with 2O (Z >5.8, p<0.01). The % M2s, 2PN fertilization rate, and BFR did not differ among groups. The median number of euploid embryos was 1.0 in each group, with a trend towards more euploids in pts with 2O (mean 2.0 vs 1.3, p<0.03). However, euploidy rate, CPR, and LBR did not differ among groups. Among 1O subgroups (left vs. right and reason for 1O), number of M2s, euploidy rate, CPR, and LBR did not differ. Pts with 1O had fewer M2s and oocytes retrieved than pts with 2O; however, had more than 50% of the number of M2s and oocytes retrieved in pts with 2O, suggesting a compensatory mechanism in the solitary ovary. In pts with 1O compared to 2O, oocyte and embryo quality, euploidy rate, and embryo transfer outcomes were similar.

Low Antimullerian Hormone Levels Improve Fertility Outcome in Patients with Polycystic Ovary Syndrome

Background: It was known that polycystic ovary syndrome (PCOS) patients have high AMH levels. The aim of this study is to show whether low AMH levels are associated with better clinical pregnancy rates in patients with PCOS. Methods: This retrospective study was performed on 443 patients with PCOS referred to BAU MedicalparkGoztepe Hospital IVF Clinic from January 2015 to October 2020. Participants ranged in age from 18 to 40, had their first two IVF trials, had performed frozen-thawed embryo transfer (FET) cycle at day 5. The diagnosis of PCOS was made using the Rotterdam criteria. Data related to patients' AMH were compared with each other, and based on the value, participants were divided into two groups: the first group was AMH≥7 (N = 49); The second group was AMH &lt;7 (N = 394). Results: The pregnancy test was positive for 288 (65%) participants. Of these participants, 214 had livebirth, 71 had miscarriages, and 3 had stillbirths. There was no significant difference in age and BMI between the two groups. There were no significant differences between the two groups in the number of stimulation days, the total number of oocytes, and MII oocytes. The numbers of frozen embryos were higher in the AMH≥7 group (p = 0.005). The positive pregnancy results were significantly higher in the AMH&lt;7 group than in the AMH≥ 7 group (P= 0.02). There was no significant difference in live birth, stillbirth, and miscarriage rates between the two groups. Conclusion: Low levels of circulating AMH are associated with better clinical pregnancy rates in patients with PCOS.

Efficacy of three COS protocols and predictability of AMH and AFC in women with discordant ovarian reserve markers: a retrospective study on 19,239 patients

BackgroundRecent studies have consistently shown that AFC and serum AMH are good predictors of ovarian response and have shown strong correlations. However, it is not unusual for reproductive medicine specialists to encounter discordance between them. This is the first study to investigate the efficacies of the different COS protocols when the AFC and AMH levels are discordant. Based on the association between COS protocols and pregnancy outcomes, we attempt to explain the controversial results and clarify the predictive value of AMH and AFC in this context.Methods19,239 patients undergoing their first fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles with GnRH antagonist protocols, GnRH-a long protocols or GnRH-a ultra-long protocols between January 1, 2016, and December 31, 2019, were enrolled and then divided into four groups in accordance with the boundaries for the AFC and serum AMH level provided by the Poseidon Classification. Our study was divided into two parts. Firstly, we retrospectively compared the effects of the three COS protocols in patients with discordant AMH and AFC. Multivariate logistic regression models were conducted in a forward manner to exclude the influence of confounding factors. Afterward, to increase comparability between Group 2 (low AMH and normal AFC) and Group 3 (normal AMH and low AFC), propensity score matching (PSM) analysis was performed based on age, BMI, the number of embryos transferred, and COS protocol. IVF intermediate and reproductive outcomes were compared between Group 2 and Group 3.ResultsFor people with low AMH and normal AFC (Group 2), the number of total oocytes, clinical pregnancy rate (CPR), live birth rate (LBR) and cumulative live birth rate (CLBR) were significantly higher in GnRH-a ultra-long protocol compared with GnRH antagonist protocol. In multivariate logistic regression models, significant associations of COS protocol with fresh LBR and CPR were found after adjusting for age, BMI, AFC, AMH and the number of embryos transferred. Whereas, in patients with normal AMH and low AFC (Group 3), the number of total oocytes, CLBR, LBR and CPR were highest in the long GnRH-a protocol although there was no statistically significant difference. After PSM, the results showed that although oocytes yield and available embryos in patients with normal AMH and low AFC were significantly higher, there was no significant difference in reproductive outcomes between Group 2 and Group 3.ConclusionsWe found that women with normal AFC and low AMH may benefit from the GnRH-a ultra-long protocol. Nevertheless, for women with normal AMH and low AFC, the long GnRH-a protocol seems to be associated with better clinical outcomes. Furthermore, after eliminating the confounding factors including the COS protocol, we found that AMH can only predict the number of oocytes but not the quality of oocytes when there was discordance between AFC and AMH.

Personal exposure to particulate matter air pollution and outcomes of ovarian stimulation: a pilot study in Massachusetts, US

BACKGROUND AND AIM: Higher exposure to ambient air pollution has been associated with lower fertility in women including specific adverse effects on ovarian steroidogenesis and folliculogenesis; however, no previous studies have measured personal exposure to air pollution which quantifies a woman’s real exposure levels. METHODS: We enrolled nine women undergoing a fresh, autologous assisted reproductive technology (ART) cycle at the Massachusetts General Hospital Fertility Center 2018-2019. At the woman’s baseline ultrasound appointment (cycle day 3), they were given an AirBeam2 monitor, which measures three size fractions of particulate matter (PM1, PM₂.₅, and PM10), a smartphone, and a 3-day activity diary. Women collected exposure data for the following 72 hours. Between cycle day 11 and 16, women underwent oocyte retrieval and information was collected on number of total and mature oocytes retrieved. Multivariable generalized linear models were used to evaluate associations between personal PM exposures and ovarian stimulation outcomes. RESULTS:Women collected PM data for an average (minimum, maximum) of 33.7 (8.4, 64.4) hours during ovarian stimulation. Their median (interquartile range [IQR]) exposure to PM1, PM₂.₅, and PM10 was 0.4 (4.1), 2.3 (5.5), 3.7 (8.3) μg/m³, respectively. After adjusting for age, stimulation protocol, infertility diagnosis, and average temperature exposure, an IQR increase in average exposure to PM1, PM₂.₅, and PM10 during cycle days 3 to 5 was associated with -26.8% (95% CI -37.6, -14.2%), -47.9% (95% CI -61.6, -29.1%), and -43.8% (95% CI -57.3, -26.0%) fewer oocytes retrieved, respectively. An IQR increase in PM1, PM₂.₅, and PM10 exposure was also associated with -18.4% (95% CI -33.9, 0.6%), -38.2% (95% CI -58.5 -8.1%), and -34.0% (95% CI -53.8, -5.6%) fewer mature oocytes retrieved, respectively. CONCLUSIONS:In this small pilot study of women undergoing ART in Massachusetts, higher personal exposure to PM during ovarian stimulation was associated with poorer oocyte yield. KEYWORDS: Air pollution, Particulate matter, Reproductive Outcomes, Short-term exposure, Environmental epidemiology

P–660 Impact of elevated late-follicular phase serum estrogen and progesterone levels on blastocyst utilization and cumulative live birth rates in freeze-all cycles

Abstract Study question Does elevated late-follicular phase estrogen and progesterone levels have an impact on blastocyst utilization and/or cumulative live birth rates in freeze-all cycles? Summary answer High estrogen or progesterone on the day of ovulation trigger is associated with poor blastocyst utilization but comparable cumulative live birth rates in freeze-all cycles. What is known already Several studies suggest impaired clinical outcome in cycles with high estrogen (&amp;gt;3500 pg/ml) or progesterone (&amp;gt;1.5 ng/ml) levels. However, these data were derived from cycles where top-quality embryo(s) were transferred in the fresh cycle and surplus embryos were frozen. These findings might be confounded by alterations in endometrial receptivity. Freeze-all cycles might provide a better model to assess the impact of high late-follicular estrogen or progesterone levels on laboratory and clinical outcome. Study design, size, duration We performed a retrospective cohort study of all IVF cycles (n = 712) between 2016 and 2018 where the entire cohort of embryos was cryopreserved at the blastocyst stage. After excluding cases with &amp;lt;4 oocytes or preimplantation genetic test, the study group comprised 459 women who had 699 frozen-thawed embryo transfer cycles. Participants/materials, setting, methods Women were classified into four groups by the indication for freeze-all strategy as elevated progesterone (high P, n = 61), high estrogen (high E, n = 224), elective freezing (elective, n = 114) and tubal-endometrial pathologies (TEP, n = 60). The primary outcome was the cumulative live birth rate in subsequent thaw-transfer cycles and the secondary outcome was the blastocyst utilization rate. Groups were compared using ANOVA and Cox regression analyses to adjust for confounding variables. Main results and the role of chance The mean age of the study group was 32.8 ± 5.3 years, total number of oocytes and cryopreserved blastocysts were 15.0±7.6 and 4.2±3.0, respectively. The high-E group was younger (31.5 ± 5.2 years) and had higher peak E2 levels (4078.9 ± 588.4 pg/ml), number of oocytes (19.7 ± 7.0), cryopreserved embryos (5.3 ± 3.3) and transfer cycles (2.3 ± 1.4) than the other groups. Blastocyst utilization rate was significantly lower (40.4%) compared to elective freezing (53.6%) and TEP groups (55.7%) (both p = 0.001). The high-P group had higher peak progesterone levels (2.1 ± 0.5 ng/ml, p = 0.001), number of oocytes (14.0 ± 5.2) and frozen embryos (4.1 ± 3.5) compared to elective and TEP groups (both p = 0.04). Blastocyst utilization rate was lower (45.7%) than elective freezing and TEP groups but the difference lacked statistical significance (p = 0.33 and p = 0.21, respectively). Cumulative live birth rates were 42.6% in high-P, 59.8% in high-E, 44.7% in elective freezing and 46.7% in TEP groups. Significant predictors of cumulative live birth were female age (aHR: 0.97, 95%CI:0.95–0.99, p = 0.02) and number of frozen blastocysts (aHR:1.05, 95%CI:1.01–1.10), p = 0.02). When adjusted for these confounders, the cumulative live birth rate was not associated with high-E (aHR: 0.86, 95%CI:0.56–1.31) or high-P (aHR: 0.76,95%CI:0.44–1.32). Limitations, reasons for caution This was a retrospective study with small sample size performed at a single fertility center, which may limit the generalizability of our findings. Wider implications of the findings: While lower blastocyst utilization rates are observed in women high late-follicular estradiol or progesterone levels, cumulative live birth rates in subsequent thaw-transfer cycles were not impaired. However, unfavorable outcome parameters observed in women with elevated progesterone deserve further research. Trial registration number Not applicable

P–614 BMI effects on oocyte quality in an egg donation program and the relationship with its first stimulation cycle

Abstract Study question Does body mass index (BMI) affect oocyte quality in an egg donation program and its relationship with the first stimulation cycle? Summary answer Our results indicated significant differences within BMI groups obtaining better results in donors &amp;lt;25 years old in quantity/quality oocyte than &amp;gt; 25 with normal weight. What is known already Low weight (LW) and excess weight represent a risk factor for different pathologies and may have a negative effect on the quality of the ovarian response in infertility treatments. Study design, size, duration Observational retrospective study at IVI Alicante, in which first donor cycles between 01/01/2015 and 04/30/2020 were analyzed. 307 donors were included. Groups were divided according to the BMI following the WHO criteria and were subdivided according to the protocol used (antagonists / progestogens, age, previous pregnancy and polycystic ovary syndrome (PCOS)). In all cases, the number of total, MII and immature oocytes, doses of FSH and days of stimulation were observed. Participants/materials, setting, methods Donors between 18–35 years old, in their first stimulation cycle, were distributed according to their BMI, following the WHO criteria in kg / m2 (Low weight (LW): &amp;lt;18, 5, Normal weight (NW): 18.5–24.9, Overweight (OW) 25–29.9 and Obese (O): ≥30). Inclusion criteria: Good state of psychophysical health and normal tests according to Spanish law on ART . Statistical analysis was performed with R statistical software, version 4.0, linear and establishing significant differences when p &amp;lt; 0.05. Main results and the role of chance Taking into account the general results of the BMI groups by oocytes number and MII: LW: 19.2 / 14.9; NW: 20.2 / 15.6; OW: 18.9 / 14.6, p = 0.513 / p = 0.74 respectively, we observe that with BMI groups and progestin stimulation protocols, results are reversed: No. oocytes and MII with LW: 30 / 22.5; NW: 19.2 / 14.4, OW: 20.8 / 14.8 p = 0.402 / 0.662 respectively. LW and OW are conditions which affect more in quantity than oocyte quality. Significant differences in BMI are observed when they are subdivided according to age, obtaining better results in donors &amp;lt;25 years of age both in quantity and oocyte quality than&amp;gt; 25 years: Total oocytes: LW: 22.6, NW: 21.7, OW: 20 vs LW: 14.2, NW: 17.6, SP: 16.3, p = 0.01, respectively; No. of MII oocytes LW: 17.8, NW: 16.6, OW: 14.9 vs LW: 10.5, NW: 13.9 OW: 13.8, p = 0.003, respectively. Our results reflect that the NW group is the one with better results obtained compared to the LW and OW groups both in overall number of oocytes and also in quality. The type of stimulation does not affect this group of donors. Limitations, reasons for caution More studies with clear criteria and a uniform record of results are needed. Meanwhile, the proper shortlisting should be considered if it is a BMI of NW (18.5–24.9 kg / m2) and less than 25 years. Wider implications of the findings: Analyzing other studies, there are disagreements in terms of discrimination of BMI groups and with incomplete data about of quantity, oocyte quality and oocyte stimulation, offering different results with the same parameters establishing trends in the NW group. Trial registration number Not applicable

P–628 Predicting oocyte yield in patients with diminished ovarian reserve using basal antral follicle count

Abstract Study question Is basal antral follicle count (bAFC) taken on day 1 to 3 of stimulation a useful predictor of oocyte yield in that cycle, in women with diminished ovarian reserve (DOR)? Summary answer Basal AFC has moderate correlation with final oocyte yield. A median 75% of the antral follicle count is collected as oocytes. What is known already The current theory of folliculogenesis suggests that all follicles available for recruitment are visible on ultrasound in the ovary at the point when ovarian stimulation is applied. This implies a tight correlation between the AFC on day 1–3 of a stimulation cycle (bAFC) and the eventual number of follicles collected. We hypothesise that in women with diminished ovarian reserve who receive maximum stimulation basal AFC would be a useful predictor of final oocyte yield in that cycle. Study design, size, duration This was a prospective single centre, observational study in a tertiary referral hospital in London. 125 women with DOR underwent controlled ovarian stimulation between December 2018 and January 2021. Participants/materials, setting, methods All study participants were given an antagonist cycle with a starting stimulation dose of 450iu and remained on the same dose throughout their treatment. We assessed the correlation between bAFC taken on day 1–3 of the stimulation cycle and the total number of oocytes collected. Main results and the role of chance A total of 150 treatment cycles were included in the analysis. The median age was 37 (IQR 35 – 39). The median AMH was 6.0 (IQR 4.4 – 8.9) and the median FSH was 7.6 (IQR 5.7 – 9.4). The median bAFC at the start was 9 (IQR 6 – 11). The median total stimulation dose was 4050iu (IQR 4050 – 4500). The median oestradiol on day of trigger was 5906 (IQR 4166 – 7397) and median number of oocytes collected was 7 (IQR 5 – 9). There was a moderate correlation between bAFC and the number of oocytes collected (r = 0.549, p = 0.005). The median ratio of oocytes collected over the number of antral follicles observed at the start was 72.7% (IQR 58.3 – 100). Limitations, reasons for caution We have standardised approach to AFC determination and have previously shown that AFC inter and intra-observer variability in our unit is low. Nevertheless, our study involved multiple operators for AFC determination which may introduce variability. Further variability may have been introduced at egg collection by varying technique. Wider implications of the findings: Studies of antagonist protocol in good prognosis patients suggest poor correlation between basal AFC and oocyte yield. In contrast, our study shows that in a population of women with DOR basal AFC provides useful information which can be used to counsel women around the expected oocyte yield of their cycle. Trial registration number Not applicable

P–325 The impact of letrozole on endometrial thickness in IVF cycles

Abstract Study question Does daily administration of letrozole during IVF stimulation affect endometrial thickness ? Summary answer Patients treated with letrozole during fresh IVF cycles had a thinner endometrium on the day of trigger compared to patients who did not receive letrozole. What is known already Letrozole supplementation is commonly used during fertility preservation for breast cancer patients to reduce peak estrogen levels with no adverse effects on embryo outcomes. Studies in poor responders have found that letrozole use resulted in a shorter duration of stimulation and a lower total dose of gonadotropin, with no detrimental effect on IVF outcomes. In normal responders, studies have shown an increase in blastocysts obtained, but have not yet shown an increase in clinical pregnancy rates. There is concern that when a fresh embryo transfer is planned letrozole use may negatively affect endometrial thickness and subsequently diminish pregnancy rates. Study design, size, duration In a retrospective cohort study between January 2009 and June 2019 at a single academic fertility center, we compared the endometrial thickness in 97 cancer patients who underwent IVF-fertility preservation with daily letrozole use to 158 cancer patients who underwent IVF-fertility preservation without letrozole. Participants/materials, setting, methods All women diagnosed with cancer were referred for fertility preservation prior to gonadotoxic treatment exposure and were less than 40 years old at the time of oocyte retrieval. All patients who received letrozole started on day one of stimulation and continued until the day of oocyte retrieval. The primary outcome was endometrial thickness on the day of trigger. The secondary outcomes were number of oocytes retrieved, number of MII retrieved, and maximal estradiol level. Main results and the role of chance During the study period, 336 cancer patients underwent fertility preservation. Eighty-one patients were excluded; 50 because they had an intrauterine device or were on long term oral contraceptives and 31 because endometrial thickness was not documented. Of the remaining 255 patients, 86 had breast cancer, 95 had a hematological cancer and 74 had various other cancers. Ninety-seven cancer patients treated with letrozole were compared to 158 cancer patients who did not receive letrozole. Patients who received letrozole were significantly older (34 vs 28yrs, P &amp;lt; 0.0001). There were no significant differences in baseline characteristics such as BMI, AFC nor in the total duration for stimulation. Endometrial thickness on the day of trigger was significantly less in letrozole treated patients (8 vs 9mm, P &amp;lt; 0.003). There were no significant differences in total number of oocytes retrieved (12.5 vs 11, P = 0.126) nor in the number of mature oocytes (8 vs 8, P = 0.312). Patients in the letrozole group received a higher total gonadotropin dose (2680IU vs 1980IU, P = 0.016). The maximum estradiol level was significantly lower in patients treated with letrozole (1068 vs 3838ml/dl, P = &amp;lt;0.0001). A regression analysis showed that using letrozole during stimulation decreased the endometrial thickness by 0.81mm (CI –1.37 to –0.253, P = 0.005). Limitations, reasons for caution The retrospective nature of this study could have introduced selection and misinformation bias. We report on cancer patients where all oocytes or embryos were vitrified. Without fresh embryo transfer data, it is unclear if a thinner endometrium due to letrozole will effect the implantation or pregnancy rate. Wider implications of the findings: As the use of letrozole expands beyond cancer patients and poor responders, it is important to understand the impact on the endometrium. This study shows that letrozole reduces endometrial thickness. However, the effect on endometrial function remains unknown. Further study is needed before letrozole can be used with fresh transfers. Trial registration number 2020–6370

O-106 Non-donor IVF treatment cycles in the UK need to be re-evaluated against the 1.625 million oocytes retrieved

Abstract Study question Are IVF clinics collecting too many oocytes per retrieval procedure? Summary answer IVF cycles performed in the UK appear to be retrieving far too many oocytes, most of which may never be used and are probably discarded. What is known already For justifying IVF with low AMH, older women, poor responders, the Bologna and POSEIDON consensuses were developed. The positive linear correlation between cumulative live birth rates and numbers of oocytes collected is well established, thereby focussing intensely on stimulation regimes and the growth of FER cycles and oocyte freezing activities. The associated risk of OHSS is well-known. However, over-stimulation practices and numbers of oocytes retrieved within IVF remain unknown as is the impact on patients’ health, emotional and financial welfare. This UK dataset uniquely reveals numbers of oocytes retrieved against IVF cycles undertaken, and which may well reflect global practices. Study design, size, duration This is a retrospective observational cohort study of oocyte retrieval procedures for non-donor IVF cycles in the UK between 2015 and 2018. Data were obtained from UK HFEA under the Freedom of Information Act 2000. For fresh oocytes, data were obtained for the number of cycles retrieving 1-5, 6-15, 16-25, 26-49, 50-59, and 60+ oocytes. The number of cycles that led to no oocytes was obtained as well as data on the utilisation of oocytes. Participants/materials, setting, methods The data from the HFEA covers up to 86 UK IVF clinics undertaking non-donor IVF. IVF clinics are legally obliged to provide IVF dataset as part of the licence requirement. The unbiased data was gathered independently by HFEA staff under the Freedom of Information Act 2000. Specifically, the number of treatment cycles with; 0, 1-5, 6-15,16-25, 26-49, 50-59, and 60+ oocytes retrieved for each year was requested. Additional limited data could be gained. Main results and the role of chance For 2015-2018 there were 172341 fresh oocyte retrieval cycles, where 10148 (5.9%) cycles from 9439 patients did not yield any oocytes. In this period, 42574 cycles (24.7%), 91797 cycles (53.3%), 23794 cycle (13.8%) and 3970 cycles (2.3%) yielded 1-5 oocytes, 6-15 oocytes, 16-25 oocytes, 26-49 oocytes respectively, while 58 cycle (0.033%) yielded over 50 oocytes. The data was accountable by 5-85 clinics and the outcomes and patterns remained uniform across the 4 years. The main desired oocyte yield of 6-15 oocytes occurred in 53.3% of IVF cycles distributed evenly across the clinics. However, 16.1% of cycles were associated with 16-49 oocytes retrieved per IVF cycle, while 58 (0.03%) cycles led to greater than 50 oocytes retrieved. The maximum number of oocytes collected was not provided by the HFEA due to technical reasons. The total number of oocytes collected over 4-years numbered 1,624,912 oocytes from 147274 women yielding on average 11 oocytes per patient. These oocytes were fertilised to yield 931,265 embryos (57.3% converted). The fate of 42.7% oocytes remains unknown. Of the embryos created, 209,080 (22.4%) were transferred over 172,333 cycles, while 219,563 (23.6%) embryos frozen and the fate of 53.97% of embryos remained unaccounted for. Limitations, reasons for caution This retrospective analysis spans 4 years in which stimulation regimes, patient characteristics, or outcomes were unavailable. Only a qualitative analysis is possible with the HFEA dataset, but the corresponding data is unique and of public interest. The outcome of unaccounted oocytes appears a limitation in the regulatory body data set. Wider implications of the findings This unique observation on IVF clinics practices suggests that the high oocyte number per retrieval procedure needs re-evaluation. In particular, this needs to focus on the side-effects, including OHSS and procedure-related complications. In addition, the outcome and cost of unused frozen oocytes need to be established. Trial registration number not applicable

P–453 Fertility preservation in endometriosis: Impact of the ovarian endometriosis and it’s surgical treatment on oocyte yield

Abstract Study question Does a previous history of surgery for ovarian endometriosis (OMA) has an impact on controlled ovarian stimulation (COS) response in case of fertility preservation (FP) for endometriosis? Summary answer After COS, a prior history for OMA surgery was associated with poorer ovarian responsiveness compared to non-previously operated women. What is known already Endometriosis is a chronic disorder that affects 10% of woman, which can be responsible for infertility. The presence of OMA and/or it’s excision could induce a reduction of the ovarian reserve (ROR), and for some women, an increased risk of premature ovarian failure. Therefore, FP with oocyte/embryo vitrification can be proposed for OMA-affected women, considering the relationship between endometriosis, infertility and ROR. Although a complete surgery excision of endometriosis lesions may be appropriate for some patients to relieve them from pain, the more efficient time to preserve fertility is still unknown in the management of women presenting OMA lesions. Study design, size, duration We conducted an observational multicentric study from April 2015 to December 2019, in two tertiary care university hospitals. Women presenting OMA or having a previous history of surgery for OMA that had performed a FP with COS for oocytes/embryo vitrification during the study period were included. Diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography and magnetic resonance imaging or histologically proven in women who had past surgery. Participants/materials, setting, methods A total of 165 women were allocated to two groups, according to the presence of a previous history of surgery for endometrioma(s). Main outcome measure was the total number of oocytes retrieved. Main results and the role of chance Fifty-one (30,9%) women were included in the group ‘previous history of surgery’ and 115 (69,1%) in the group ‘no history of surgery’. Mean age was 31,6±4,4 years and was not significantly different between groups (p = 0.09). However, women in ‘No previous surgery’ group had higher AMH levels than women in ‘previous surgery’ group (2.27±1.70ng/ml versus 1.56±1.89ng/ml; p &amp;lt; 0,001). In the group ‘previous history of surgery’, 21(41.2%) women had a recurrence of OMA(s) and 31 (60.8%) had at least one deep infiltrating endometriosis (DIE) lesion at FP. In the group ‘no history of surgery’, 92(80.7%) of the women had DIE. In addition, women in ‘No previous surgery group’ had larger OMA than women in ‘previous surgery’ group (mean diameter size: 5.56±4.34cm versus 3.25±2.16cm, respectively; p:0,03). The mean number of COS with oocyte-retrieval was significantly higher in the group ‘previous history of surgery’ (2.0±1.02 versus 1.65±0.82 in the group ‘no surgery’, p = 0.03), however, the total number of oocytes retrieved per women was significantly higher in women ‘history of surgery’, compared to women ‘no previous surgery’ (13.7±8.4 versus 10.3±7.5, p = 0.02). In addition, the cancellation rate per cycle was significantly lower in ‘No previous surgery’ group compared to the ‘previous surgery’ group (0.09±0.31 versus 0.28±0.53; p &amp;lt; 0.001). Limitations, reasons for caution No data concerning the thawing of oocytes/embryo are available for now. Wider implications of the findings: FP is an essential component to integrate in ovarian endometriosis-management and should be proposed before surgery to optimize oocyte yield. Trial registration number Not applicable

Frozen eggs: national autologous oocyte thaw outcomes

To characterize national outcomes of oocyte thaw (OT) cycles. Retrospective descriptive study. All autologous OT cycles reported to the Society of Assisted Reproductive Technology Clinic Outcome Reporting System from 2012 to 2018. All women undergoing OT cycles in the United States. None. Absolute numbers of oocyte cryopreservation (OC) and OT cycles over time. Among OT cycles, patient and cycle characteristics, the ratio of the total number of oocytes thawed to the number of live births by maternal age at the time of cryopreservation (ATOC), and outcomes including pregnancy, miscarriage, live birth, and good perinatal outcome (GPO) by age ATOC. From 2012 to 2018, 54,675 OC and 6,413 OT cycles were performed; the absolute numbers increased from 2,719 to 13,824 and from 348 to 1,810, respectively. The ratio of the total number of oocytes thawed to the number of live births increased significantly with increasing age ATOC, from 41.4 (age <35 years) to 122.4 (age >41 years). Among OT cycles resulting in embryo transfer, the live birth rate decreased with increasing age ATOC from 42.8% (age <35 years) to 10.8% (age >42 years). The live birth rate was higher when calculated per transfer (42.8% in women aged <35 years ATOC) rather than per thaw cycle (31.5% in women aged <35 years ATOC) because of the number of patients with no transfer. Among 1,124 cycles resulting in pregnancy, the chance of a GPO was highest among women aged <35 years ATOC (65.8%) and decreased as age at ATOC increased. Among reported OT cycles, the rates of pregnancy and live birth decreased as age ATOC increased. The number of oocytes thawed to achieve one live birth increased significantly with increasing age ATOC. In addition, among the resulting pregnancies, the rate of GPO decreased as age ATOC increased.

Improvement in early antral follicle development and gene expression modulation prior to follicle aspiration in bovine cumulus-oocyte complexes by equine chorionic gonadotropin

We aimed to evaluate the morphological ovarian response to equine chorionic gonadotropin (eCG) prior to ovum pick-up (OPU) and its effects on the molecular phenotype of immature cumulus-oocyte complexes (COCs) from Nelore cow (Bos indicus) donors. To this end, 20 Nelore cows were distributed randomly into the synchronized-OPU (Sync-OPU) and synchronized plus stimulated-OPU (Sync + eCG-OPU) groups using a cross-over experimental design, as each cow was used in both treatments. On a random day of the estrus cycle (Day 0), all cows received an intravaginal implant with 1.0 g of progesterone and 2 mg IM of estradiol benzoate. On the morning of Day 3, only the Sync + eCG-OPU group received 400 IU of eCG IM. On the morning of Day 5, the P4 device was removed and OPU was conducted in both groups. Before OPU management, ultrasonography was used to identify and measure the follicles. The aspirated COCs were morphologically classified based on their cumulus cells (CC) layers and the texture of the ooplasm. The COCs classified as Grade 1, Grade 2, and Grade 3 were considered viable and used for the assessment of quality markers. Oocytes and CC were mechanically separated from pools of 25 immature COCs of the Sync-OPU and Sync + eCG-OPU groups immediately after the follicular aspiration and stored at −80 °C until RNA extraction. Relative quantification of several markers for oocyte quality was assessed by RT-qPCR. The eCG treatment increased the number of follicles sized 3.0–5.0 mm and >5.0 mm compared to that in Sync-OPU group. Moreover, the protocol with eCG improved the total number of oocytes and the number of viable oocytes, which is related to a high number of oocytes in Grade 3. Regarding the impact on transcriptional regulation in immature oocytes, the mRNA encoding BMP15, SMAD1, SMAD2, SMAD3, ACACA, and CPT1A was upregulated in Sync + eCG-OPU compared with the Sync-OPU group. Moreover, the relative mRNA abundance of CTSZ, a member of the cathepsins family functionally related to reduced oocyte competence, was lower in the Sync + eCG-OPU group than in the Sync-OPU group. In addition, CC CTSB, CTSS, and CTSK mRNA abundances were lower in the Sync + eCG-OPU group than in the Sync-OPU group. However, the relative abundance of AREG and EREG mRNA was higher in CC recovered from cows stimulated with eCG. In conclusion, the eCG approach addressing follicular stimulation in Nelore cows had a positive impact on early antral follicle development, followed by a positive morphological and molecular phenotype in bovine COCs.

Testicular sperm extraction vs. ejaculated sperm use for nonazoospermic male factor infertility

To study the potential benefit of testicular sperm compared with ejaculated sperm for men with oligospermia. After exemption from institutional review board approval, we performed a retrospective cohort study using the Mayo Clinic Assisted Reproductive Technology database. Single academic center. Couples with nonazoospermic male factor infertility (total motile sperm <25 million per ejaculate) undergoing intracytoplasmic sperm injection with sperm obtained by testicular sperm extraction (TESE) or ejaculated sperm between 2016 and2019. Invitro fertilization, Intracytoplasmic sperm injection, TESE. The primary outcome was live birth rate. The secondary outcomes were fertilization rate, blastulation rate, pregnancy rate, and miscarriage rate. Subjects in the two groups were similar in age, body mass index, and ovarian reserve. Baseline sperm parameters were similar in the two groups: total motile sperm (5.4 in the ejaculate sperm group vs. 3.6 million motile per ejaculate), except that baseline motility was higher in the group that used ejaculated sperm (40% vs. 29%). The total number of mature oocytes retrieved was similar in the two groups, but the use of TESE was associated with a 20% decrease in fertilization (60.0% vs. 80.6%) and half the number of blastocyst embryos (two vs. four) compared with ejaculated sperm. Compared with ejaculated sperm, use of TESE did not improve the miscarriage rate (11% vs. 9%) or the live birth rate (50.0% vs. 31.3%). Patients with male factor infertility and oligozoospermia did not have improved ICSI outcomes with the use of TESE samples compared with ejaculated sperm.

VARIATION IN CYCLE CHARACTERISTICS AMONG PATIENTS < 35 WITH A SINGLE DIAGNOSIS

BackgroundInfertile women under 35 are among those considered to have a favorable prognosis with regards to assisted reproductive technology (ART) cycles. However, although reproductive age is the best predictor of outcome with ART, this population has a heterogeneous result with regards to live birth outcomes. Cycle characteristics, e.g. fertilization and embryo development, represent a potential counseling tool with which to manage patient expectations through an ART cycle. We hypothesized that infertility diagnosis would be associated with cycle characteristics among patients with ovarian (e.g. diminished ovarian reserve/DOR), anatomic (tubal factor/TF) and unexplained infertility.ObjectiveThe purpose of this study was to evaluate cycle characteristics among patients with DOR, TF, and unexplained infertility.Materials and MethodsA retrospective chart review of fresh autologous IVF cycles in patients < 35 years of age with a single diagnosis of unexplained infertility, tubal factor, or diminished ovarian reserve (DOR) performed at an academic center between 2010 and 2019 were identified. Patients with more than one identified indication for ART were excluded from analysis. Cycle characteristics were defined as total gonadotropin dose, number of oocytes retrieved, fertilization rate and total number of embryos for transfer and cryopreservation. ANOVA with post-hoc Tukey HSD was performed on variable outcomes.ResultsA total of 332 cycles were evaluated. In cycles with women < 35 years of age with a single diagnosis, unexplained infertility (46%; 153/332 cycles) was the most common single diagnosis, followed by DOR (36%; 119/332 cycles) and TF (18%, 60/332). No differences were observed in mean ages among unexplained (31.1 +/- 7.4 years), DOR (31.1 +/- 2.7 years), and TF (30.9 +/- 2.6 years) infertility (p=0.8). DOR cycles exhibited lower AMH values (1.5 +/- 1.62 ng/ml) versus unexplained infertility (3.27 +/- 1.84 ng/ml, p=0.002), higher total FSH dose (3801 +/- 1977 versus 2090 +/- 1005 mIU/mL, p<0.001), and lower total number of oocytes retrieved (9.3 +/- 5.3 versus 15.1 +/- 7.4, p<0.0001). No difference was observed in AMH, total FSH dose, and total number of oocytes retrieved between unexplained infertility and TF cycles. No statistically significant difference was seen in fertilization rates between the three groups (p=0.2); however, total number of embryos available for either transfer or cryopreservation was highest in tubal factor patients (7.1 +/- 6.6) compared to both unexplained (4.7 +/- 3.9, p<0.01) and DOR (3.7 +/- 3.0, p<0.001).ConclusionsDespite similar markers of ovarian reserve, total number of oocytes retrieved and fertilization rates, patients with unexplained infertility exhibit lower numbers of total embryos available for transfer or cryopreservation compared to those with TF infertility. These data suggest embryonic development as a potential contributor to ART outcomes in unexplained infertility.SUPPORT: N/A

Factors predicting clinical outcomes from 494 vitrified oocyte donation cycles at a UK-regulated egg bank

Research questionDo donor age, AMH, AFC, BMI and reproductive history predict response to ovarian stimulation? Do donor and recipient clinical markers and embryology parameters predict recipient pregnancy and live birth? DesignRetrospective cohort study of 494 altruistic oocyte donors aged 18–35 years; 340 were matched to 559 recipients. Predictors of donor total oocyte yield and total mature oocyte yield were identified. Total and mature oocyte number were compared according to stratified donor AMH and age. Donor, recipient and embryology parameters predictive of recipient primary outcomes (clinical pregnancy and live birth) were identified. ResultsDonor age and AMH predicted total oocyte yield (P = 0.030 and P < 0.001)) and total mature oocyte yield (P = 0.011 and P < 0.001). Donors aged 30–35 years with AMH 15–29.9 pmol/l had lower total oocyte yield (P = 0.004) and mature oocyte yield (P < 0.001) than donors aged 18–24 years. Up to an AMH threshold of 39.9 pmol/l, increasing AMH levels predicted higher total oocyte yield (<15 pmol/l versus 15–29.9 pmol/l, P = 0.001; 15–29.9 pmol/l versus 30–39.9 pmol/l, P < 0.001; 30–39.9pmol/l versus ≥ 40 pmol/l, P = 1.0) and mature oocyte yield (<15 pmol/l versus 15–29.9 pmol/l, P = 0.005; 15–29.9 pmol/l versus 30–39.9 pmol/l, P = 0.006; 30–39.9 pmol/l versus ≥40 pmol/l, P = 1.0). In recipients, the rate of transferrable embryos per oocytes received, fertilized and number of embryo transfers needed to achieve the primary outcome were predictors of cumulative clinical pregnancy (P = 0.011, P = 0.017 and P < 0.001) and live birth (P = 0.008, P = 0.012 and P < 0.001) rates. Recipient BMI (P = 0.024) and previous miscarriages (P = 0.045) were predictors of cumulative live birth rate. Donor age 18–22 years was associated with a lower incidence of recipient clinical pregnancy (P = 0.004) and live birth (P = 0.001) after the first embryo transfer versus donor age 23–29 years. ConclusionsDonor age and AMH are independent predictors of oocyte yield. Raised recipient BMI and history of miscarriages reduce cumulative live birth rates, which may be increased by selecting donors aged 23–29 years, instead of younger donors.

Assisted reproductive technique outcomes in patients with endometrioma undergoing sclerotherapy vs laparoscopic cystectomy: Prospective cross-sectional study.

PurposeThe authors compared assisted reproductive technique (ART) outcomes and the recurrence rate of endometrioma in the infertile patients undergoing sclerotherapy vs laparoscopic ovarian cystectomy.MethodsIn this prospective cross‐sectional study, a total of 101 infertile patients, with unilateral endometriomas, were divided into two groups. The first group (n = 57) underwent ART after 1 year of unsuccessful spontaneous pregnancy after laparoscopic ovarian cystectomy; the second group (n = 44) had ethanol sclerotherapy (EST) at the time of oocyte retrieval. The authors measured the number of oocytes, clinical pregnancy rate (CPR), live birth rate (LBR), complication, and recurrence of endometriomas as the primary and secondary outcomes.ResultsThe two groups had no significant differences in baseline characteristics and ovarian stimulation markers and also total number of oocytes. 42.1% and 34.1% of the patients (n = 24 and 15) had clinical pregnancy, and 38.6% and 29.5% (n = 22 and 13) had live birth following ART cycles in the surgery group and sclerotherapy group (P = .41, 0.34). The recurrence rates were 14.0% and 34.1% in the surgery and sclerotherapy groups (P = .017, X 2 = 5.67).ConclusionsEthanol sclerotherapy can be a good alternative to surgery concerning the treatment of endometrioma; however, the recurrence of the disease in this group is significantly higher.

Viability of bovine opu-derived oocytes to honeybee as cryoprotectant

This study designs to determine the effectiveness of Honeybee (HB) as cryoprotectants (CP) on viability vitrified-thawed bovine oocytes derived from OPU using Trehalose as control. Cattles were subjected to superstimulation protocol, per session conducted five days where three days both cattle were administrated 100 mg follicle stimulation hormone (FSH) within 24 h once and two days of “resting period” totalling two sessions. The “coasting period” (FSH starvation) between sessions was four days (96 h). Oocytes collection via OPU were performed at fifth day (120 h). The ovarian growth was observed via ultrasonographic before OPU. Prior to vitrifying oocytes with treatment Trehalose (T1) and HB (T2) followed by warming protocol, oocytes subjected to in vitro maturation (IVM). Oocytes viability were evaluated by fluorescein diacetate staining. Results showed ovarian growth for first session was larger size follicles than the second session for both cattle. Total number of oocytes obtained were 60. Oocytes viability treatment T2 was significantly higher (90.9%) than T1 (70.4%). This study concludes that HB as CP in vitrification protocol was able to achieved high oocytes viability with oocytes derived via OPU suggesting Honeybee as an alternative CP for oocytes vitrification.

Senataxin: A New Guardian of the Female Germline Important for Delaying Ovarian Aging.

Early decline in ovarian function known as premature ovarian aging (POA) occurs in around 10% of women and is characterized by a markedly reduced ovarian reserve. Premature ovarian insufficiency (POI) affects ~1% of women and refers to the severe end of the POA spectrum in which, accelerated ovarian aging leads to menopause before 40 years of age. Ovarian reserve refers to the total number of follicle-enclosed oocytes within both ovaries. Oocyte DNA integrity is a critical determinant of ovarian reserve since damage to DNA of oocytes within primordial-stage follicles triggers follicular apoptosis leading to accelerated follicle depletion. Despite the high prevalence of POA, very little is known regarding its genetic causation. Another little-investigated aspect of oocyte DNA damage involves low-grade damage that escapes apoptosis at the primordial follicle stage and persists throughout oocyte growth and later follicle development. Senataxin (SETX) is an RNA/DNA helicase involved in repair of oxidative stress-induced DNA damage and is well-known for its roles in preventing neurodegenerative disease. Recent findings uncover an important role for SETX in protecting oocyte DNA integrity against aging-induced increases in oxidative stress. Significantly, this newly identified SETX-mediated regulation of oocyte DNA integrity is critical for preventing POA and early-onset female infertility by preventing premature depletion of the ovarian follicular pool and reducing the burden of low-grade DNA damage both in primordial and fully-grown oocytes.