Is It Possible to Expand Oocyte Donors by Decreasing Number of Oocytes for Own Use? Insights From a Large Single-Center Study.

Background: Currently, in China, only women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles can donate oocytes to others, but at least 15 oocytes must be kept for their own treatment. Thus, the aim of this study was to determine whether oocyte donation compromises the cumulative live birth rate (CLBR) of donors and whether it is possible to expand oocyte donors' crowd. Methods: This was a retrospective cohort study from August 2015 to July 2017 including a total of 2,144 patients, in which 830 IVF-embryo transfer (IVF-ET) patients were eligible for oocyte donation and 1,314 patients met all other oocyte donation criteria but had fewer oocytes retrieved (10-17 oocytes). All 830 patients were advised to donate approximately three to five oocytes to others and were eventually divided into two groups: the oocyte donation group (those who donated) and the control group (those who declined). The basic patient parameters and CLBR, as well as the number of supernumerary embryos after achieving live birth, were compared. These two factors were also compared in all patients (2,144) with oocyte ≥10. Results: In 830 IVF-ET patients who were eligible for oocyte donation, only the oocyte number was significantly different between two groups, and the donation group had more than the control group (25.49 ± 5.76 vs. 22.88 ± 5.11, respectively; p = 0.09). No significant differences were found between the two groups in other factors. The results indicate that the live birth rate in the donation group was higher than that in the control group (81.31% vs. 82.95%, p = 0.371), without significance. In addition, CLBR can still reach as high as 73% when the oocyte number for own use was 10. Supernumerary embryos also increased as the oocyte number increased in all patients (oocyte ≥10). Conclusions: Currently, oocyte donation did not compromise CLBR, and oocyte donation can decrease the waste of embryos. In addition, in patients with 10 oocytes retrieved, the CLBR was still good (73%). Thus, it is possible to expand oocyte donors if the number of oocyte kept for own use was decreased from 15 to 10 after enough communication with patients.

Effects of half-dose and full-dose GnRH antagonists on IVF-ET outcomes: a retrospective study.

BACKGROUND: Gonadotropin-releasing hormone antagonist(GnRH-ant) has been shown to have a negative effect on endometrial receptivity. Therefore, the use of lower doses of GnRH-ant during controlled ovarian stimulation (COS) may improve endometrial receptivity and clinical pregnancy rate. However, the GnRH-ant dose is relatively flexible and there is no fixed requirement for guidance. In this retrospective study, we determined the effects of half-dose and full-dose GnRH-ant on IVF-ET outcomes. METHODS: Of the 316 cycles in the 314 patients analyzed in this study, 149 received GnRH-ant half-dose (Group1), while 167 received GnRH-ant full-dose (Group2). The groups were further classified based on age and BMI. Age subgroups, were divided as age ≤ 35(subgroup A) and age > 35(subgroup B): 180 cycles in subgroup A (107 cycles in subgroup A1,73 cycles in subgroup A2), 136 cycles in subgroup B (42 cycles in subgroup B1,94 cycles in subgroupB2). The subgroups based on BMI were divided as BMI < 25 (subgroup C)and BMI ≥ 25 (subgroup D):208 cycles in subgroup C (94 cycles in subgroup C1,114 cycles in subgroup C2), 108 cycles in subgroup D (55 cycles in subgroup D1,53 cycles in subgroup D2). RESULTS: The number of fertilized oocytes, superior-quality embryos, clinical pregnancy rate, and live birth rate differed significantly between the two groups. However, the number of retrieved oocytes and available embryos were significantly higher in Group 1 than Group 2 (8.17 ± 4.10 vs. 7.07 ± 4.05, 2.96 ± 2.03 vs. 2.52 ± 1.62, respectively,p<0.05). Differences between the age subgroups were not statistically significant. However, in the subgroups based on BMI, the fertilized oocytes, available embryos, the number of superior-quality embryos, and the live birth rate differed significantly between the four subgroups. The number of retrieved oocytes was higher in subgroup C1 than in subgroup C2 (8.24 ± 4.04 vs. 6.83 ± 3.92,p < 0.05), In addition, the clinical pregnancy rate was slightly higher in subgroup D1 than in subgroup D2(45.45 vs. 24.53%, P < 0.05). CONCLUSIONS: The results showed that half-dose GnRH-ant was as effective as full-dose GnRH-ant for most patients. Moreover, half-dose GnRH-ant may be more suitable in patients with BMI greater than or equal to 25. The findings of this study need to be validated in a large sample RCT. TRIAL REGISTRATION: Retrospectively registered.

Fertility preservation and PGT-M in women with familial adenomatous polyposis-associated desmoid tumours.

RESEARCH QUESTION: Is ovarian stimulation and pregnancy in women with familial adenomatous polyposis (FAP)-associated desmoid tumours safe? DESIGN: The study included women with FAP-associated desmoid tumours who underwent fertility treatments at the authors' tertiary medical centre between the years 2011 and 2021. Data were collected from the fertility unit's charts and from the oncological registries. The main outcome measures were the number of vitrified oocytes and embryos, and the number of live births in preimplantation genetic testing for monogenic/single gene defects (PGT-M) cycles. RESULTS: Overall, 17 women were identified suitable for this study. A total of 117 mature oocytes were vitrified for fertility preservation and 106 embryos were submitted to PGT-M. One patient returned to claim her cryopreserved oocytes, and five patients who underwent PGT-M embryo transfer reported three live births. A statistically significant decrease in selected fertility cycle parameters was observed in one woman who co-administered sorafenib (a multikinase inhibitor) during her first cycles of treatment, as the mean number of oocytes before and after was 2.7 (±1.3) versus 13.2 (±3.3) (P = 0.02), the mean number of metaphase II oocytes was 2.2 (±2.1) versus 7.7 (±2.6) (P = 0.007), and the mean number of two-pronuclei oocytes was 0.5 (±1.1) versus 3.5 (±1.7) (P = 0.09). Three patients had a median desmoid tumour growth on magnetic resonance imaging of 6.2 (2.9-7.2) cm when compared with prior ovarian stimulation imaging. CONCLUSIONS: Ovarian stimulation for women with desmoid tumours was characterized in some patients with an acceleration in tumour growth, regardless of the use of aromatase inhibitors. The use of sorafenib should be carefully considered during the course of fertility treatment.

Oocyte accumulation for fertility preservation in women with benign ovarian tumours with a history of previous surgery, multiple or large cysts.

RESEARCH QUESTION: What are ovarian stimulation cycle outcomes and acceptance rates of an oocyte accumulation programme in young women with benign ovarian tumour (BOT)? DESIGN: Retrospective cohort study conducted at the Academic Assisted Reproductive Technology and Fertility Preservation Centre, Lille University Hospital, between January 2016 and December 2019. The number of metaphase II oocytes per cycle and per patient after accumulation were evaluated. Two groups were identified for the analysis: endometrioma ('endometrioma') and dermoid, mucinous or serous cyst ('other cysts'). RESULTS: A total of 113 fertility-preservation cycles were analysed in 70 women aged 27.9 ± 4.8 years. Almost all women had undergone previous ovarian surgery before fertility preservation (89%). Mean anti-Müllerian hormone levels before ovarian stimulation was 12.5 ± 8.7 pmol/l. A total of 6.4 ± 3.4 oocytes were retrieved, and 4.3 ± 3.4 metaphase II (MII) oocytes were vitrified per cycle. All agreed to the oocyte accumulation programme and all underwent at least one cycle. To date, 36 (51%) patients achieved two or three fertility- preservation cycles. After accumulation, 7.0 ± 5.23 MII oocytes were vitrified per patient. No difference was found in ovarian response and oocyte cohort between the 'endometrioma' and 'other cysts' groups. Questionnaires completed after oocyte retrieval revealed abdominal bloating and pelvic pain in most patients, with no difference according to the type of cyst. No serious adverse events occurred. CONCLUSIONS: Oocyte accumulation should be systematically offered to young women with BOT irrespective of histological type, as it seems to be well-tolerated. Long-term follow-up is needed to assess the efficiency of oocyte accumulation to optimize the chances of subsequent pregnancies.

How far is too far? Does time interval between GnRH antagonist and GnRH agonist trigger in GnRH antagonist cycles matter?

RESEARCH QUESTION: What is a suitable time interval between the last GnRH antagonist exposure and GnRH agonist (GnRHa) triggering for final follicular maturation? DESIGN: A retrospective cohort study including 413 patients undergoing GnRH antagonist cycles in which GnRHa trigger was used, either solely or as a dual trigger. The primary outcome measure was the follicle/mature oocyte ratio. Cycles were analysed according to the time interval between the last GnRH antagonist exposure and the GnRHa triggering: Group 1 included patients with a 12-14 h interval; Group 2: 7-10 h interval; Group 3: 5-6 h interval and Group 4: 2-4 h interval. LH concentration was measured 11-13 h post-GnRHa injection. RESULTS: Median LH value was 65 IU/l. There was a weak but significant correlation between basal LH and the LH surge (R2 = 0.137, P < 0.001). Although square root LH values differed significantly between study groups (P < 0.001; higher in Groups 2 and 3), the follicle/mature oocyte ratio was not different across the four antagonist-agonist interval groups and no correlation was detected between the post-trigger LH concentration and the follicle/oocyte ratio (R2 = 0.011). In a model integrating age, day 3 FSH concentration, maximal oestradiol and body mass index along with the study groups, none of these factors was significantly related to the follicle/mature oocyte outcome ratio. Insufficient surge (LH < 15 IU/l) occurred in 14 (3.4%) cases. Rates of insufficient LH surge did not differ significantly between the groups (2.4%, 3.2%, 3.4% and 7.1% in Groups 1 to 4, respectively; P = 0.5). CONCLUSIONS: LH concentrations post-GnRHa trigger differ in regard to antagonist-agonist intervals, but the follicle/mature oocyte ratio achieved was not affected.

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

RESEARCH QUESTION: Do 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? DESIGN: Retrospective 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. RESULTS: Donor 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. CONCLUSIONS: Donor 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.

Oocyte or embryo number needed to optimize live birth and cumulative live birth rates in mild stimulation IVF cycles.

RESEARCH QUESTION: How many oocytes or embryos are needed to optimize the live birth rate (LBR) per cycle and cumulative LBR (CLBR) following mild stimulation IVF (MS-IVF) in women with uncompromised ovarian reserve? DESIGN: Retrospective analysis of a 4-year database of five fertility centres. The study population included women with normal/high ovarian reserve, who underwent autologous MS-IVF (daily ≤150 IU gonadotrophin) with fresh and subsequent frozen embryo transfer(s) (FET) from surplus embryos. Only the first cycle of each patient was included. Cycles with >150 IU daily average of gonadotrophin were excluded. 'Freeze-all embryo' (FAE) cycles were analysed separately. RESULTS: A total of 862 consecutive cycles fulfilled the inclusion criteria; 592 were eligible for fresh embryo transfer, 239 had non-elective 'freeze-all' cycles. Median age (25-75th percentile) of women who had fresh embryo transfer was 35 (32-37) years, median antral follicle count 19 (14-28) and anti-Müllerian hormone 19.2 (13-28.9) pmol/l. LBR/fresh cycle and CLBR inclusive of FAE cycles in the <35, 35-37, 38-39 and 40-42 year age groups were 37.8% and 45.1%, 36.0% and 41.6%, 18.4% and 29.1%, and 8.9% and 18.1%, respectively. The LBR following fresh embryo transfer plateaued after nine oocytes (40.3%) or four embryos (40.8%). The CLBR optimized when 12 oocytes (42.9%) or nine embryos (53.8%) were obtained. The LBR per oocyte peaked in women under 35 years when <5 oocytes were retrieved (11.4%), then declined with age and with higher oocyte yield. There were no cases of severe ovarian hyperstimulation syndrome (OHSS). CONCLUSION: Nine oocytes, or four embryos, can optimize fresh transfer cycle LBR in MS-IVF. The CLBR are optimized with 12 oocytes, or nine embryos in predicted normal responders, while safeguarding against OHSS.

Predicting the Likelihood of Live Birth in Assisted Reproductive Technology According to the Number of Oocytes Retrieved and Female Age Using a Generalized Additive Model: A Retrospective Cohort Analysis of 17,948 Cycles.

Capsule: We designed a predictive reference model to evaluate how many stimulation cycles are needed for a patient to achieve an ideal live birth rate using assisted reproductive technology. Objective: To develop a counseling tool for women who wish to undergo assisted reproductive technology (ART) treatment to predict the likelihood of live birth based on age and number of oocytes retrieved. Methods: This was a 6-year population-based retrospective cohort analysis using individual patient ART data. Between 2012 and 2017, 17,948 women were analyzed from their single ovarian stimulation cycle until they had a live birth or had used all their embryos. All consecutive women between 20 and 49 years old undergoing their ovarian stimulation cycles for ART in our center were enrolled. The cumulative live birth rate (CLBR) was defined as the delivery of a live neonate born during fresh or subsequent frozen-thawed embryo transfer cycles. Only the first delivery was considered in the analysis. Binary logistic regression was performed to identify and adjust for factors known to affect the CLBR independently. A generalized additive model was used to build a predictive model of CLBR according to the woman's age and the number of oocytes retrieved. Results: An evidenced-based counseling tool was created to predict the probability of an individual woman having a live birth, based on her age and the number of oocytes retrieved in ART cycles. The model was verified by 10 times 10-fold cross-validation using the preprocessed data, and 100 area under the curve (AUC) values for receiver operating characteristic (ROC) curves were obtained on the test set. The mean AUC value was 0.7394. Our model predicts different CLBRs ranging from nearly 90% to less than 20% for women aged 20-49 years with at least 22 oocytes retrieved. The CLBRs of women aged 20-28 years were very similar, nearly on one trend line with a certain number of oocytes retrieved. Differences in the CLBR began to appear by the age of 29 years; these increased gradually in women aged >35 years. Conclusion: A predictive model of the CLBR was designed to serve as a guide for physicians and for patients considering ART treatment. The number of oocytes needed to be retrieved to achieve a live birth depends on the woman's age.

FSH dose is negatively correlated with number of oocytes retrieved: analysis of a data set with ~650,000 ART cycles that previously identified an inverse relationship between FSH dose and live birth rate.

PURPOSE: To evaluate whether total FSH dose was negatively correlated with number of oocytes retrieved in a large data set where previously, a negative correlation between FSH dose and live birth rate was identified. METHODS: Data from 650,637 fresh autologous in vitro fertilization (IVF) cycles reported to the Society for Assisted Reproductive Technology between 2004 and 2012 were included. Logistic regression analysis was performed to determine if the relationship between total FSH dose used during ART with number of oocytes retrieved was impacted by the patient's health prognosis, age, BMI, ovarian stimulation protocol, or infertility diagnosis. RESULTS: The number of oocytes retrieved was negatively correlated with FSH dose (P < 0.0001). Regardless of patient prognosis, age, BMI, ovarian stimulation protocol, and infertility diagnosis, the highest number of oocytes retrieved was in the 1001-2000 IU FSH group, and was 36-51% lower in the > 5000 IU compared with the optimal, 1001-2000 IU, FSH groups. Overall, ~80% of patients received FSH doses outside of the optimal FSH dose. Moreover, 61% of good prognosis patients (excludes individuals likely prescribed higher FSH doses) received doses exceeding the optimal dose range. CONCLUSION: The inverse relationship between FSH dose and the number of oocytes retrieved independent of patient age or health implies that excessive FSH doses during ART may be detrimental to oocyte retrieval.

IVF in women aged 43 years and older: a 20-year experience.

RESEARCH QUESTION: What are the reproductive outcomes of women aged 43 years and older undergoing IVF and intracytoplasmic sperm injection (ICSI) treatment using their own eggs. DESIGN: Retrospective study of 833 woman aged 43 years or older undergoing their first IVF and ICSI cycle using autologous oocytes at a tertiary referral hospital between January 1995 and December 2019. Live birth rate (LBR) after 24 weeks' gestation was the primary outcome. RESULTS: Ninety-five out of 833 (11.4%) had a positive HCG, whereas 59 (62.1% per positive HCG) had a miscarriage before 12 weeks' gestation and 36 (4.3%) live births were achieved. Analysis by age showed that the number of cumulus-oocyte complexes retrieved was significantly different between the four age groups: 43 years (5 [3-9]); 44 years (5 [2-7]); 45 years (3 [2-8)]); ≥45 years (2.5 [2-6]); P < 0.01; the number of metaphase II oocytes, however, was similar. Positive HCG rates remained low: 43 years (78/580 [13.4%]); 44 years (14/192 [7.3%]); 45 years (1/39 [2.6%]; and ≥46 years (2/22 [9.1%]); P = 0.03, as did LBR: 43 years (28 [4.8%]); 44 (7 [3.6%]); 45 years (0 [0%]); and ≥46 years (1 [4.5%]); P = 0.5. Multivariate regression analysis revealed that only number of metaphase II was significantly associated with LBR, when age was considered as a continuous (OR 1.08, 96% CI 1.004 to 1.16) or categorical variable (OR 1.08, 95% CI 1.005 to 1.16). CONCLUSION: The chances of achieving a live birth in patients aged 43 years and older undergoing IVF/ICSI with their own gametes are low, even in cases of patients with a relatively 'normal' ovarian reserve for their age.

Luteal Phase Ovarian Stimulation versus Follicular Phase Ovarian Stimulation results in different Human Cumulus cell genes expression: A pilot study.

Background: Luteal-phase ovarian stimulation (LPOS) is an alternative in vitro fertilization (IVF) protocol. However, limited data showed the genes expression of cumulus cells (CCs) in LPOS. Therefore, this study aimed to investigate CC genes expression between LPOS and follicular-phase ovarian stimulation (FPOS) in poor ovarian responders (PORs) undergoing IVF cycles. Methods: This was a prospective non-randomized trial (ClinicalTrials.gov Identifier: NCT03238833). A total of 36 PORs who met the Bologna criteria and underwent IVF cycles were enrolled. Fifteen PORs were allocated to the LPOS group, and 21 PORs were allocated to the FPOS group. The levels of CC genes involved in inflammation (CXCL1, CXCL3, TNF, PTGES), oxidative phosphorylation (NDUFB7, NDUFA4L2, SLC25A27), apoptosis (DAPK3, BCL6B) and metabolism (PCK1, LDHC) were analyzed using real-time quantitative PCR and compared between the two groups. Results: The number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day-3 embryos and top-quality day-3 embryos, clinical pregnancy rates and live birth rates were similar between the two groups except for significantly high progesterone levels in the LPOS group. The mRNA expression levels of CXCL1 (0.51 vs 1.00, p < 0.001) and PTGES (0.30 vs 1.00, p < 0.01) were significantly lower in the LPOS group than in the FPOS group. The LPOS group had significantly lower mRNA expression of NDUFB7 (0.12 vs 1.00, p < 0.001) and NDUFA4L2 (0.33 vs 1.00, p < 0.01) than the FPOS group. DAPK3 (3.81 vs 1.00, p < 0.05) and BCL6B (2.59 vs 1.00, p < 0.01) mRNA expression was significantly higher in the LPOS group than in the FPOS group. Increased expression of PCK1 (3.13 vs. 1.00, p < 0.001) and decreased expression of LDHC (0.12 vs. 1.00, p < 0.001) were observed in the LPOS group compared to the FPOS group. Conclusions: Our data revealed different CC genes expression involving in inflammation, oxidative phosphorylation, apoptosis and metabolism between LPOS and FPOS in PORs. However, the results are non-conclusive; further large-scale randomized controlled trials are needed to validate the results.

Do follicular fluid advanced glycation end products levels affect the ovarian response in unexplained infertility?

OBJECTIVE: To compare the advanced glycation end products (AGEs) levels in follicular fluid according to the different ovarian responses of women who underwent controlled ovarian stimulation due to unexplained infertility and to examine the relationship between these levels and pregnancy outcomes. METHODS: Sixty-three women who underwent fresh IVF/ICSI cycles with GNRH antagonist protocol were divided into 3 groups according to the number of retrieved oocytes as suboptimal (4-9 oocytes), optimal (10-15 oocytes) and high (>15 oocytes) responders. AGEs levels in follicular fluid were measured by ELISA method. RESULTS: AGEs levels were 6.81 ± 2.20 µg/ml, 5.30 ± 2.01 and 6.44 ± 1.43 µg/ml in suboptimal, optimal and high response group, respectively. AGEs level was significantly higher in suboptimal response group than in optimal response group. The cutoff level of 6.19 µg/ml had a sensitivity of 59.3% and a specificity of 66.7% in distinguishing the suboptimal response group from the optimal response group. However, there were no statistically significant difference between AGEs levels and clinical pregnancy and live birth rates. CONCLUSION: Increased AGEs level in follicular fluid may be associated with decreased ovarian response during controlled ovarian stimulation in unexplained infertility case, however, it does not provide information about pregnancy outcomes.

Time from oocyte retrieval to frozen embryo transfer in the natural cycle does not impact reproductive or neonatal outcomes.

OBJECTIVE: To determine if the time from oocyte retrieval to frozen embryo transfer (FET) in the natural cycle affects reproductive or neonatal outcomes. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): Five hundred and seventy-six consecutive freeze-all cycles from January 2011 to December 2018 followed by natural cycle FET of a single blastocyst. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome of live birth; secondary outcomes of preterm delivery (24-37 weeks) and small for gestational age (SGA) with a multivariable logistic regression performed with adjustment for age, infertility diagnosis, ovulatory trigger type, and preimplantation genetic testing (PGT). RESULT(S): Before adjustment for confounding, we found a statistically significantly different live-birth rate (57.7% vs. 48.6%) for natural cycle FET occurring in the first versus second menstrual cycle, respectively. In a multivariate analysis, performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle did not statistically significantly impact the odds of live-birth rate. After adjustment for age, diagnosis, and ovulatory trigger type, only PGT was associated with statistically significantly increased odds of live birth compared with no PGT. There were no differences in the incidence of SGA (male, 6.6% vs. 2.3%; female, 9.8% vs. 11.1%) or preterm delivery (1.6% vs. 5.6%) between both groups. CONCLUSION(S): Performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle after ovarian stimulation did not statistically significantly impact the odds of live birth or neonatal outcomes.

Ideal lag time from ovulation to oocyte aspiration using a GnRH agonist trigger.

BACKGROUND: In ART, oocyte maturation (M2) and ovulation is stimulated by a hormonal trigger. For maturation to occur, sufficient "lag time" must elapse between the trigger and aspiration, ranging from 32 to 38 hours. Premature aspiration can result in poor yields; late aspiration risks spontaneous ovulation. AIM: Our study examines optimal lag time using a GnRH antagonist protocol and GnRH agonist trigger for ICSI. METHODS AND MATERIALS: We analyzed data from 220 women undergoing GnRH antagonist protocol using a GnRH agonist trigger for ICSI at our clinic between 02/2012-03/2018. Patients were divided into 4 groups based on lag time: 34.00-34.99 hours (n = 32), 35.00-35.99 hours (n = 113), 36.00-36.99 hours (n = 57) and 37.00 h or more (n = 18). Analyses were performed with the Kruskal-Wallis test, Chi-Square, and Spearman's rho correlation. RESULTS: A positive correlation was found for the number of M2 oocytes aspirated and lag time (ρ = 0.138, p = 0.04) and for the total number of oocytes aspirated and lag time, (ρ = 0.174, p = 0.01). No correlation was found between the proportion of M2 oocytes aspirated and lag time (p = 0.217). The third group (36 h) had significantly more M2 oocytes aspirated than the second group (35 h) (12.4 ± 7.1 vs 9.4 ± 6.2; p = 0.039). The four groups did not differ for the proportion of mature M2 oocytes (H = 2.453, p = 0.484). The four groups differed in the frequency of live births per fresh embryos transferred (χ2 = 9.364, p = 0.025). CONCLUSION: Our study identified a positive correlation between lag time and both the number of M2 oocytes and the total number of oocytes aspirated-factors which lead to an increased rate of successful pregnancies. Further research is necessary.

Is there an optimal number of oocytes retrieved at which live birth rates or cumulative live birth rates per aspiration are maximized after ART? A systematic review.

The association between the number of oocytes retrieved and fresh live birth rate (LBR) or cumulative LBR (CLBR), and whether an optimal number of oocytes are retrieved when LBR or CLBR are maximized, are highly relevant clinical questions; however published results are conflicting. A systematic review of all eligible studies (n = 16) published until January 2020 on MEDLINE, Embase, Scopus, CINAHL and Web of Science was conducted. Five studies evaluated only LBR from fresh cycles, five studies evaluated only CLBR from stimulated cycles and six evaluated both. A marked difference was observed between the oocyte yields at which LBR and CLBR were reportedly maximized in the individual studies. On the basis of nine studies, the optimal number of oocytes at which fresh LBR seems to be maximized is proposed to be between 12 and 18 oocytes (15 oocytes was the most common suggestion). On the other hand, CLBR continues to increase with the number of oocytes retrieved. This is the first systematic review on the topic, and it suggests that the retrieval of 12-18 oocytes is associated with maximal fresh LBR, whereas a continuing positive association is present between the number of oocytes retrieved and CLBR.

Ovarian response to stimulation for fertility preservation in women with hematologic cancer.

PURPOSE: To compare the ovarian response to controlled ovarian hyperstimulation (COH) in patients with hematologic malignancies treated for fertility preservation (FP) and healthy subjects (oocyte donors (OD)). PATIENTS AND METHODS: Retrospective cohort study comparing 41 women (18-37 years) who underwent COH for oocyte vitrification prior to gonadotoxic treatment for hematologic cancer (FP group) from January 2014 to February 2019 and with 117 women undergoing COH as part of an OD protocol (OD group) during the same period. The number of frozen mature oocytes, number of oocytes retrieved, total dose of rFSH, maximal estradiol levels, percentage of maturity, number of dominant follicles >14 mm, days of stimulation were evaluated. Results were adjusted for age, body mass index (BMI), anti-Mullerian hormone (AMH) and rFSH starting dose. RESULTS: Patients in the FP group were younger and had a lower BMI than those in the OD group. rFSH starting dose was higher in the FP group (median 225UI (125;450) vs 150UI (87.5;337.5), p < 0.0001). After adjusting for age, BMI and starting rFSH dose according to ANCOVA, more frozen mature oocytes (median 10 (0;45) vs 8 (0;22] p = 0.0055) and retrieved oocytes (median 12 (0;49) vs 11 (0;29) p = 0.0468) were found in the FP group. Other outcome measures did not differ between the groups. CONCLUSION: Ovarian response after COH in women with a hematologic cancer is similar to that in the general population. A higher number of mature oocytes were collected in the FP group after strong COH.

Reproductive and obstetric outcomes in mildly and significantly underweight women undergoing IVF.

RESEARCH QUESTION: What is the impact of low body mass index (BMI) on live birth rates and obstetric outcomes in infertile women treated with IVF and fresh embryo transfer? DESIGN: This was a retrospective cohort study of infertile patients in an academic hospital setting who underwent their first oocyte retrieval with planned autologous fresh embryo transfer between 1 January 2012 and 31 December 2018. The primary study outcome was live birth rate. Secondary outcomes were IVF treatment and delivery outcomes. Underweight patients were stratified into a significantly underweight group (body mass index [BMI] <17.5 kg/m2) and a mildly underweight group (BMI 17.5-18.49 kg/m2), and were compared with a normal-weight group (BMI 18.5-24.9 kg/m2). RESULTS: A total of 5229 patients were included (significantly underweight, 76; mildly underweight, 231; normal weight, 4922), resulting in 4798 embryo transfers. After oocyte retrieval, there were no significant differences between groups for total oocytes, mature oocyte yield and number of supernumerary blastocysts cryopreserved. Among women who had an embryo transfer, there were no significant differences in the live birth rates in significantly (31.0%, odds ratio [OR] 0.67, confidence interval [0.95, CI] 0.40-1.13) and mildly (37.7%, OR 0.95, CI 0.73-1.33) underweight patients compared with normal-weight patients (35.9%). Additionally, there were no statistically significant increased risks of preterm delivery, Caesarean delivery or a low birthweight (<2500 g) neonate. CONCLUSIONS: Mildly and significantly underweight infertile women have similar pregnancy and live birth rates to normal-weight patients after IVF treatment. In addition, underweight patients do not have an increased risk of preterm delivery (<37 weeks), Caesarean delivery or a low birthweight neonate.

Streamlining follicular monitoring during controlled ovarian stimulation: a data-driven approach to efficient IVF care in the new era of social distancing.

STUDY QUESTION: What is the optimal follicular tracking strategy for controlled ovarian stimulation (COS) in order to minimise face-to-face interactions? SUMMARY ANSWER: As data from follicular tracking scans on Days 5, 6 or 7 of stimulation are the most useful to accurately predict trigger timing and risk of over-response, scans on these days should be prioritised if streamlined monitoring is necessary. WHAT IS KNOWN ALREADY: British Fertility Society guidance for centres restarting ART following coronavirus disease 2019 (COVID-19) pandemic-related shutdowns recommends reducing the number of patient visits for monitoring during COS. Current evidence on optimal monitoring during ovarian stimulation is sparse, and protocols vary significantly. Small studies of simplifying IVF therapy by minimising monitoring have reported no adverse effects on outcomes, including live birth rate. There are opportunities to learn from the adaptations necessary during these extraordinary times to improve the efficiency of IVF care in the longer term. STUDY DESIGN, SIZE, DURATION: A retrospective database analysis of 9294 ultrasound scans performed during monitoring of 2322 IVF cycles undertaken by 1875 women in a single centre was performed. The primary objective was to identify when in the IVF cycle the data obtained from ultrasound are most predictive of both oocyte maturation trigger timing and an over-response to stimulation. If a reduced frequency of clinic visits is needed due to COVID-19 precautions, prioritising attendance for monitoring scans on the most predictive cycle days may be prudent. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study comprised anonymised retrospective database analysis of IVF/ICSI cycles at a tertiary referral IVF centre. Machine learning models are used in combining demographic and follicular tracking data to predict cycle oocyte maturation trigger timing and over-response. The primary outcome was the day or days in cycle from which scan data yield optimal model prediction performance statistics. The model for predicting trigger day uses patient age, number of follicles at baseline scan and follicle count by size for the current scan. The model to predict over-response uses age and number of follicles of a given size. MAIN RESULTS AND THE ROLE OF CHANCE: The earliest cycle day for which our model has high accuracy to predict both trigger day and risk of over-response is stimulation Day 5. The Day 5 model to predict trigger date has a mean squared error 2.16 ± 0.12 and to predict over-response an area under the receiver operating characteristic curve 0.91 ± 0.01. LIMITATIONS, REASONS FOR CAUTION: This is a retrospective single-centre study and the results may not be generalisable to centres using different treatment protocols. The results are derived from modelling, and further clinical validation studies will verify the accuracy of the model. WIDER IMPLICATIONS OF THE FINDINGS: Follicular tracking starting at Day 5 of stimulation may help to streamline the amount of monitoring required in COS. Previous small studies have shown that minimal monitoring protocols did not adversely impact outcomes. If IVF can safely be made less onerous on the clinic's resources and patient's time, without compromising success, this could help to reduce burden-related treatment drop-out. STUDY FUNDING/COMPETING INTEREST(S): F.P.C. acknowledges funding from the NIHR Applied Research Collaboration Wessex. The authors declare they have no competing interests in relation to this work. TRIAL REGISTRATION NUMBER: N/A.

Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals.

RESEARCH QUESTION: What are the risk factors affecting the incidences of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and severe hemoperitoneum in assisted reproductive technology (ART) treatment cycles? DESIGN: A retrospective cohort study was conducted on 1,435,108 oocyte retrieval cycles among Japanese ART registry data between 2007 and 2015. The study included 11,378 cycles with moderate-to-severe OHSS, 1182 cycles with severe hemoperitoneum, including 27 cycles with both conditions, and 1,422,575 cycles without moderate-to-severe OHSS and severe hemoperitoneum. RESULTS: The incidences of moderate-to-severe OHSS and severe hemoperitoneum were 0.79% and 0.08%, respectively, and decreased by 0.57-fold and 0.29-fold from 2007 to 2015, respectively. In cycles with OHSS and cycles with hemoperitoneum women were younger (odds ratios [OR] 0.91 and 0.95, respectively) and had more retrieved oocytes (OR 1.09 and 1.01, respectively) compared with cycles without both complications. The use of a gonadotrophin-releasing hormone (GnRH) agonist protocol for ovarian stimulation was the highest risk factor in cycles with OHSS and hemoperitoneum (OR 1.83 and 1.24, respectively), followed by GnRH antagonist protocol (reference), gonadotrophin with or without oral medicine (OR 0.45 and 0.56, respectively) and natural or oral medicine (OR 0.02 and 0.19, respectively). In fresh embryo transfer, clinical pregnancy was associated with an increased risk of OHSS and hemoperitoneum (OR 1.19 and 2.34, respectively). CONCLUSIONS: The highest risk factors affecting OHSS and hemoperitoneum were the use of a GnRH agonist protocol and clinical pregnancy following fresh embryo transfer. The incidences of OHSS and hemoperitoneum have decreased yearly with a reduction of GnRH agonist use and fresh embryo transfer.

The effect of human papilloma virus vaccination on embryo yield and clinical in vitro fertilisation outcomes: a matched retrospective cohort study.

The effects of HPV vaccination on embryo yield and pregnancy outcomes in IVF cycles with fresh embryo transfer (ET) were investigated. First, embryo yielding rates (EYR) in 2795 cycles with and without HPV vaccination were compared by retrospective cohort study design. EYR of HPV vaccinated and non-vaccinated patients were not significantly different (OR, 1.66; 95% CI, 0.76-3.63). Second, ET outcomes were compared for 155 HPV vaccine + cycles and 465 HPV vaccine - cycles after matching for ages and cycle attempt number. The differences in the number of retrieved oocytes (10.2 ± 6.1, 11.2 ± 6.7; p = .161), mature (MII) oocytes (8.7 ± 5.7, 9.8 ± 6.3; p = .088), two pronuclear zygotes (2PN) (5.4 ± 4.1, 6.1 ± 4.6; p = .110) and fertilisation rates (0.62 ± 0.23, 0.62 ± 0.23; p = .539) were insignificant between the two groups. Moreover, positive (OR, 0.74; 95% CI, 0.47-1.16), clinical (0.60; 0.36-1.01) and the ongoing pregnancy (0.55; 0.30-1.01) rates were lower in the HPV vaccinated group but the difference was not statistically significant.IMPACT STATEMENTWhat is already known on this subject? There are recent case studies that report premature ovarian insufficiency (POI) following a post-vaccination autoimmune response against the HPV vaccine. These studies suggest that the possible trigger for the immune reaction might be the immunogen content of the vaccine. However, the number of clinical studies investigating the effects of the HPV vaccine on reproductive function and in vitro fertilisation outcomes is limited.What do the results of this study add? In contrast to the case reports suggesting impaired reproductive and ovarian functions in HPV vaccinated patients, this study finds that in IVF patients HPV vaccinated and non-vaccinated women have similar EYR, MII, 2PN, oocyte counts, fertilisation rates, positive, clinical and ongoing pregnancy rates.What are the implications of these findings for clinical practice and/or further research? The results suggest the HPV vaccine does not have a negative impact on embryo yielding rates oocyte counts and fertilisation rates, positive, clinical and ongoing pregnancy rates in IVF treatments. Hence, they can be safely used for primary prevention against cervical cancer.