Total Number Of Mature Oocytes Research Articles

Spironolactone use and oocyte maturation in patients undergoing controlled ovarian hyperstimulation.

To evaluate the association between spironolactone use and controlled ovarian hyperstimulation (COH) outcomes. Retrospective study, including patients who underwent COH. Oocyte yield and maturation rates were compared by categories of spironolactone use at the start of their cycle. 402 patients were included. 83 patients continued spironolactone, 44 patients discontinued spironolactone, and 275 matched control patients were spironolactone-naïve. No difference was observed in the number of oocytes retrieved (17 ± 14 vs. 15 ± 13, p = 0.4) or mature oocytes vitrified (15 ± 9.5 vs. 12 ± 11, p = 0.4) in patients who continued spironolactone use and spironolactone naïve patients, respectively. When comparing patients who continued spironolactone use and patients who discontinued spironolactone use, no difference was seen in the number of oocytes retrieved (17 ± 14 vs. 17.5 ± 7.8, p = 0.9) or mature oocytes vitrified (15 ± 9.5 vs. 13.5 ± 6.5, p = 0.5), respectively. There was no observed relationship between total daily spironolactone dose (< 100mg/day, 100mg/day, 150mg/day and > 200 mg/day) and the total number of mature oocytes vitrified (respectively, 14.0 ± 13.0, 16.0 ± 7.8, 14.0 ± 4.5, 11.0 ± 7.0 oocytes, p = 0.4). This is the first study to evaluate the association between spironolactone and oocyte yield and maturation rates during COH cycles. These findings can assist in counseling patients on the implications of continuing spironolactone during COH cycle.

P-166 An artificial intelligence-powered tool to score fresh donor oocytes and predict blastulation: interim analysis of a prospective investigation conducted at 3 laboratories

Abstract Study question Is the Magenta-score associated with fresh donor oocytes’ blastulation competence, and can it be used to predict blastocyst rates per cohort of inseminated oocytes (BRpC)? Summary answer Developmentally-competent fresh donor oocytes showed significantly higher Magenta-score, although the number of blastocysts obtained was within the predicted range in only 63% of the cycles. What is known already Currently, many couples undergo donor oocyte treatments. However, despite donors being theoretically fertile, not all oocytes are developmentally competent, and many do not reach the blastocyst stage. Even if subjective and ineffective to predict oocyte competence, visual oocyte morphological assessment is still routinely used to evaluate oocytes. Lately, the rise of artificial intelligence (AI) resulted in promising tools to assess oocytes more objectively in a standardized method, possibly providing novel insights into the prediction of their competence. In this context, Magenta-score (Future Fertility), an AI-based image analysis tool, can potentially prove useful to optimize the management of oocyte donation treatments. Study design, size, duration A Blinded cohort study (June-2023/December-2023) was conducted to assess the primary outcome: association between fresh donor-oocytes’ Magenta-Score and their subsequent blastocyst development (assumed to be 50%). A sample size of 779 achieves 80%-power to detect the difference between the null-hypothesis point-biserial-correlation of 0 and the alternative hypothesis of 0.1 using a two-sided test with 5%-significance. Secondary outcomes were differences (i) predicted - true BRpCs, and (ii) predicted - true numbers of blastocysts obtained. Participants/materials, setting, methods Interim-analysis of 514 fresh-oocytes obtained from 63 donors at 3 centers and allocated (7.7±3, range:3-18) to 67 recipients. Pictures of denuded mature oocytes were acquired before ICSI. Magenta-scores were generated blindly (providing only donor age and total number of mature oocytes in cohort to the software). The software also estimated BRpCs and range of blastocysts obtainable from each cohort. Donors’ characteristics, ovarian stimulation/treatment cycle parameters, and sperm analyses were tested as confounders. Main results and the role of chance The only visual oocyte anomaly associated with lower Magenta-score was irregular shape (N = 484,5.4±2.2 vs N = 30,3.3±2.1, Mann-Whitney-U&amp;lt;0.01). Oocytes that developed into blastocysts (N = 194) had significantly higher Magenta-scores versus oocytes that did not reach this milestone (N = 320) (5.8±2.1 vs 4.9±2.3, Mann-Whitney-U&amp;lt;0.01; Odds-Ratio adjusted for sperm motility and incubator [standard/time-lapse]=1.26, 95%CI:1.13-1.34, p &amp;lt; 0.01; power=99.6%). No association was noted with day of blastulation or morphological quality. Data were concordant across centers. The average predicted-BRpC was 39.4±11.4% versus a true-BRpC of 40.6±22.6% (Person’s correlation: -0.24; mean difference: -1.1±27.6%, 95%CI from -7.8% to + 5.6%, p = 0.74). The average predicted number of blastocysts per oocyte cohort was 3.3±1.6 versus a true average of 2.9±1.7 (Person’s correlation: 0.25; mean difference: +0.4±2.0, 95%CI from -0.04 to + 0.9, p = 0.07). In 21% (N = 14) and 31% (N = 21) of cycles, the tool predicted an equal or lower number of blastocysts, respectively. In 5 cycles, no blastocyst was obtained, but the tool did not predict this unexpected outcome. When testing the predicted range of blastocysts obtained, the true number was within the range in 63% (N = 42) of cases and higher than the maximum predicted number in 13% (N = 9) of cases. No confounder was identified on the BRpC in this population of fresh donor cycles. Limitations, reasons for caution Of note, this is an interim analysis of an ongoing study. Not all mature oocytes recovered from a donor were utilized, thus not all oocytes in a cohort were imaged and included in analysis. Other putative confounders on BRpC should be considered in future studies with a larger sample size. Wider implications of the findings Effective management of an oocyte donation program is critical to comply with expected high success rates while minimizing the number of surplus blastocysts produced. The integration of genomic data, recipient couples’ characteristics, and the benefits of objective standardized AI-powered oocyte scoring is the most promising workflow to optimize this task. Trial registration number Not applicable

Oocyte cryopreservation with in vitro maturation for fertility preservation in girls at risk for ovarian insufficiency.

To assess the feasibility and outcomes of oocyte cryopreservation with in vitro maturation (IVM) in post-pubertal girls undergoing fertility preservation (FP) for primary ovarian insufficiency (POI) risk. Ovarian stimulation was performed with an antagonist protocol or progesterone priming. Ultrasound monitoring was performed transabdominally. Oocytes were retrieved transvaginally under IV sedation. Immature oocytes were subjected to IVM for up to 36h. All MII oocytes were vitrified. The main outcome measure was the total number of mature oocytes cryopreserved. The secondary outcome was the increase in the mature oocyte yield after IVM. Indications for FP included mosaic Turner syndrome (mTS; n = 10), malignancy (n = 3), and POI risk (n = 2). The mean ± SD age, antral follicle count (AFC), and AMH levels were 14.2 ± 1.4years, 8 ± 5.2 and 1.3 ± 1.3ng/mL. In girls with mTS, the ovarian reserve was low for age (AFC 7.4 ± 4.7 and AMH 1.4 ± 1.6ng/mL). Oocyte cryopreservation was possible in all girls with a range of 1-27 mature oocytes obtained, even in those who were previously exposed to chemotherapy or with low ovarian reserve, and no surgical complications were encountered. After IVM, the median mature oocyte yield increased significantly from 7.5 to 10.5 (p = 0.001). Oocyte cryopreservation appears to be feasible and safe in girls as young as 12years of age at risk for POI The utility of IVM increases the yield of cryopreserved mature oocytes. Prior exposure to chemotherapy or low ovarian reserve should not be an automatic reason to exclude these girls from FP consideration.

Effects of reduced follicle-stimulating hormone dosage before human chorionic gonadotropin trigger on in vitro fertilization outcomes

ObjectiveTo determine whether a reduced dose of follicle-stimulating hormone (FSH) before human chorionic gonadotropin (hCG) trigger during ovarian stimulation can affect in vitro fertilization (IVF) outcomes.MethodsThis study included 347 patients with a normal ovarian response who received a reduced dose of FSH before hCG trigger for 2–3 days (Group A) and 671 patients who did not receive a reduced dose (Group B) from a university-affiliated IVF center between January 2021 and December 2022. The primary endpoint was estrogen (E2) and progesterone (P) levels on the day of hCG trigger, fresh embryo transfer cycles, laboratory outcomes, and clinical outcomes between the two groups.ResultsOn the day of hCG trigger, Group A had significantly lower E2 and P levels than those in Group B (3454.95 ± 1708.14 pg/mL versus 3798.70 ± 1774.26 pg/mL, p = 0.003; and 1.23 ± 0.53 ng/mL versus 1.37 ± 0.59 ng/mL, p < 0.001, respectively). The proportion of patients with P levels ≥ 1.5 ng/mL was 22.48% in Group A compared to 34.58% in Group B (p < 0.001), while the proportion of patients with E2 ≥ 5000 pg/mL was 15.27% in Group A compared to 25.93% in Group B (p < 0.001). The fresh embryo-transfer cycle rate in Group A was higher than that in group B (54.47% and 32.64%, respectively; p < 0.001). Despite the reduction in FSH dosage, there were no significant differences between groups regarding the number of oocytes retrieved, total number of mature oocytes, normal fertilization rate, cleavage rate, Day 3 top-quality rate, implantation rate, pregnancy rate per cycle, and early pregnancy loss rate.ConclusionWhile a reduced dose of FSH prior to hCG trigger during ovarian stimulation did not significantly affect IVF outcomes, it was associated with lower E2 and P levels, resulting in fewer cycles with E2 ≥ 5000 pg/mL and P ≥ 1.5 ng/mL on the day of the hCG trigger.

P-268 Artificial intelligence (AI) image analysis outperforms patient age as a surrogate marker for oocyte quality, demonstrating an increased accuracy in predicting blastocyst development

Abstract Study question Can an AI image analysis tool (VIOLET) provide better predictions of oocyte potential than the current standard, patient age, as it relates to blastocyst development? Summary answer While increasing patient age slightly correlates with decreases in blastocyst development, VIOLET provides personalized assessments of individual oocytes correlated to blastocyst development with improved accuracy. What is known already Increasing patient age correlates to decreases in oocyte competency, leading to greater challenges in successful fertility treatment. Clinically, patient age is used to estimate probabilities of success based on national databases. Such as the case in oocyte cryopreservation cycles, considering only age and number of mature oocytes vitrified. However, oocyte quality may vary widely between patients of the same age, and even within each cohort of oocytes. VIOLET is an AI tool that assesses images of mature denuded oocytes to provide an analysis shown to significantly correlate with subsequent blastocyst development and quality, consistently outperforming embryologists in this task. Study design, size, duration This large-scale retrospective study assessed 9,120 mature denuded oocytes retrieved during 2014-2022, representing 1,384 patients between ages 19-49, attending 7 fertility clinics across 5 countries. The VIOLET prediction model is based on image analysis of mature denuded oocytes, without incorporating clinical variables, such as age. Patient age was used to build a separate predictive model of blastocyst development (10,947 training and 3,750 validation samples) to assess the predictive value of age in comparison to VIOLET. Participants/materials, setting, methods Blastocyst development was determined by embryos achieving a Gardner grade by Day5/6 post-ICSI. Blastocyst rates per oocyte cohort were calculated by number of blastocysts divided by total number of mature oocytes retrieved. Various machine learning techniques were trialed to build the predictive model strictly using age; with Random Forest model providing the best-balanced performance. VIOLET and the age model assessed the images and age of 9,120 mature denuded oocytes, respectively, providing predictions of blastocyst development. Main results and the role of chance Blastocyst development was significantly different between patients &amp;lt;35 years old compared to those ≥35 years old [47% vs 42%; p &amp;lt; 0.05 by Two Proportion Z-test]; however, not when the older age group was stratified further. On a patient level, the cohort of oocytes was evaluated by the blastocyst development ratio. Among four age groups (&amp;lt;35, 35-37, 37-40, &amp;gt;40), the blastocyst development ratios per cohort were very similar, with overlapping distributions of 84-94% using Kernel Density estimates. Thus, patient age group does not provide enough information to explain blastocyst development success for an individual oocyte or within an oocyte cohort. In comparison, VIOLET probability is significantly correlated to blastocyst development (p &amp;lt; 0.05; Welch’s Two sample t-test). And blastocyst development rates display a stepwise positive correlation that is significantly different between VIOLET probability quartiles [24% vs 39% vs 47% vs 53%; p &amp;lt; 0.05 by Two Proportion Z-test], providing meaningful information on individual oocytes. Additionally, the predictive model built with age as the only feature had poor ability to predict blastocyst success of an individual oocyte with a limited area-under-the-curve (AUC) of 0.5—unable to separate positive and negative classes. This was outperformed by VIOLET, which displayed an AUC of 0.62 on the same unseen dataset. Limitations, reasons for caution Increasing maternal age causes increased chromosomal abnormalities in oocytes, which translates to lower efficacy with treatment outcomes; therefore, further research to assess VIOLET correlation with PGT-A and implantation outcomes is needed and underway. Wider implications of the findings Patient age correlates with blastocyst development on a general level; however, it does not provide meaningful insights to distinguish rates of blastocyst success on an individual oocyte or oocyte cohort level. VIOLET augments oocyte understanding over the current standard of care, which can be utilized to support personalized clinical decision-making. Trial registration number Not applicable.

The effectiveness of controlled ovarian stimulation with tamoxifen for patients with estrogen-sensitive breast cancer: A systematic review and meta-analysis.

Tamoxifen is used for the suppression of estrogen-sensitive tumor recurrence in oocyte retrieval cycles. This meta-analysis aimed to evaluate the quality of controlled ovarian stimulation (COS) with co-administration of gonadotropins and tamoxifen (COS with tamoxifen). PubMed, Embase, and Cochrane Library were searched for articles on October 30, 2022. The authors included studies comparing COS with tamoxifen and COS with gonadotropins and letrozole (COS with letrozole) or gonadotropin only (COS with gonadotropin only) for fertility preservation in patients with breast cancer. The main outcome measures were the COS quality, total number of retrieved oocytes (TOR), total number of mature oocytes (TMO), and peak estradiol levels (PEL). Four studies (348 patients, two randomized controlled trials, and two cohort studies) were included in our meta-analysis. There was no significant difference in TOR (95% CI, [-3.84, 2.90]) and TMO (95% CI, [-2.20, 2.64]) between COS with tamoxifen and COS with letrozole. There was also no difference in TOR (95% CI, [-6.14, 1.86]) between COS with tamoxifen and COS with gonadotropin only. Statistically significant decrease was observed in PEL during COS with letrozole compared with tamoxifen (95% CI, [1414.4, 4953.7]). The quality did not differ between COS with tamoxifen and COS with letrozole or gonadotropin only.

P-649 Impact of systemic FSH levels on the embryo ploidy status in ovarian stimulation for IVF/ICSI

Abstract Study question Does systemic serum FSH-level per mature oocyte (FSH/MII) on the day of final oocyte maturation affect the ploidy status of the embryo cohort? Summary answer Higher serum FSH/MII levels negatively affect the euploid rate of the embryo cohort. What is known already In ovarian stimulation cycles, follicular phase systemic FSH-levels have to be kept above a certain threshold to achieve and maintain multifollicular growth. This contrasts the natural pattern, where FSH-levels decline steadily in the later follicular phase as a result of the increasing estrogen level. Until now, it is unclear, whether this unphysiological pattern of the systemic FSH course has an influence on the ploidy status of the biopsied blastocysts. Study design, size, duration Retrospective study performed at a tertiary ART referral center, including 582 cycles between March 2017 and December 2020. All GnRH (Gonadotropin-Releasing-Hormone) antagonist stimulation cycles used only recombinant FSH as gonadotropin. Patients aged between 19 and 48. All embryos underwent Preimplantation Genetic Testing for Aneuploidies (PGT-A) by Next Generation Sequencing with trophectoderm biopsy. Patients with surgical sperm extraction or warmed oocytes were excluded. Participants/materials, setting, methods Patients with primary or secondary infertility and an indication for ovarian stimulation for IVF/ICSI with PGT-A were included. Ovarian stimulation cycles were monitored according to clinical routine by ultrasound and repeated measurement of FSH, estradiol (E2), progesterone (P4) and LH throughout the cycle. The FSH/MII ratio was calculated as the ratio of the systemic FSH-level on the day of trigger (DoT) to the total number of mature oocytes (MII) after denudation. Main results and the role of chance FSH-levels at DoT revealed a wide range of systemic levels, from 2.12 to 47 IU/L. Patients had a mean age (±SD) of 30.49±4.99 years, Body Mass Index (BMI) of 27.58±5.14 kg/m2, Anti-Müllerian Hormone (AMH) of 4.20±3.05 ng/ml and 17.54±8.63 oocytes were collected with the oocyte pick up procedure. In the univariate analysis, a significant negative correlation was found between euploid rate and the FSH/MII ratio (β=-3.194, p &amp;lt; 0.001). Other parameters found to be negatively correlated were age (β=-1.055, p &amp;lt; 0.001), systemic FSH-level at DoT (β=-0.652, p &amp;lt; 0.01), total stimulation dose (β=-0.477, p &amp;lt; 0.01) and basal FSH-level (β=-1.605, p &amp;lt; 0.05). Alternatively, basal antral follicle count (AFC; β = 0.416, p &amp;lt; 0.05) and total follicle count at DoT (β = 0.507, p &amp;lt; 0.01) were observed to have a positive significant correlation with the euploid rate. After adjusting for potential confounders in a multivariate analysis, three parameters were still observed to be significantly correlated: FSH/MII ratio remained a negative factor for euploid rate (β=-2.753, p &amp;lt; 0.01) besides the parameters age (β=-0.837, p &amp;lt; 0.01) and E2 at DoT (β=-0.439, p &amp;lt; 0.05). Limitations, reasons for caution The retrospective character of this study can be seen as a limitation as well as the fact that the results cannot be translated to patients using either only HMG, or a combination of recombinant FSH and HMG for ovarian stimulation. Wider implications of the findings Due to the fact that higher FSH/MII ratios are associated with a decreased euploid rate, FSH-level measurements should be introduced into ovarian stimulation monitoring, as the gonadotropin dosage might be adjusted according to the systemic FSH-levels. This represents a further step on the treatment individualization towards a more personalized medicine. Trial registration number not applicable

Exploring the Developmental Potential of Human Germinal Vesicle Oocytes Aiming at Fertility Preservation: Can We Increase the Yields of Competent Oocytes through IVM Combined with Vitrification?

The rescue in vitro maturation (rIVM) of germinal vesicle oocytes (GVs) has been proposed to improve the total number of mature oocytes in women undergoing fertility preservation. Currently, there is no consensus about the clinical utility of this practice, and heterogeneity in the protocols used may influence the final outcomes. This study investigated the developmental potential of mature metaphase II (MII) human oocytes obtained from GVs after rIVM and the impact of applying vitrification at different timepoints either before or after rIVM. After randomization, oocytes were assigned to undergo rIVM and thereafter vitrification or intracytoplasmic sperm injection (ICSI), or to undergo direct vitrification-warming and thereafter rIVM and ICSI. The likelihood of obtaining MII oocytes was just slightly higher in the fresh rIVM group compared to the vitrification-warming-rIVM group. When comparing fresh rIVM that underwent subsequently ICSI, the fertilization and developmental rates up to the blastocyst stage were seen to be reduced in both groups that underwent vitrification either before or after rIVM. Although some blastocysts were obtained in the fresh rIVM-ICSI group, the efficacy of these methods was low overall, suggesting that the further development of protocols for IVM conducted early after denudation is needed to improve the final results of rIVM aiming at fertility preservation.

Unexplained Total Fertilization Failure after Intracytoplasmic Sperm Injection Cycles: A Case-Control Study on Predictive Factors and Retreatment Prognosis.

BackgroundThe aim of our study was to detect the rate of unexplained total fertilization failure (TFF) after intracytoplasmic sperm injection (ICSI) and identify its risk factors and retreatment prognosis.Materials and MethodsIn this retrospective case-control study, we searched the computerized database of the Royan Institute (Tehran, Iran) from March 2015 to March 2019 and retrieved all cases diagnosed with TFF after ICSI. TFF cases that did not have any recognized risk factors were classified as unexplained (subgroup A). Cases with recognized risk factors were classified as subgroup B. The control group was randomly selected from infertile couples who underwent ICSI cycles with fertilization of at least one oocyte during the same time interval. Characteristics and treatment outcomes of the cases with unexplained TFF (subgroup A) were compared to the control group, and to the other TFF cases (subgroup B).ResultsOut of 18,750 couples who underwent ICSI cycles, 296 (1.58%) experienced TFF for the first time. Of these, 49 (16.5%) couples were diagnosed as unexplained TFF (subgroup A) and 247 (83.5%) were placed in subgroup B, TFF with expected risk factors. Multivariable logistic regression analysis showed that the total number of mature oocytes (P<0.001), duration of infertility (P=0.043), and women’s body mass index (BMI, P<0.001) were significant predictive factors for unexplained TFF. In the ICSI cycle after TFF, clinical pregnancy and live birth rates in subgroup A were higher than subgroup B. Although differences between these groups were not statistically significant (P=0.14 and P=0.07, respectively), this finding could be clinically important.ConclusionUnexplained TFF following ICSI is a rare event significantly related to a lower number of mature oocytes, longer duration of infertility and higher female BMI. It has a good prognosis in retreatment cycles in comparison with expected TFF cases. Clinicians should take this into consideration for patient counseling and management.

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.

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.

Blastocyst conversion rate and ploidy in patients with structural rearrangements.

The primary objective of this study was to test the hypotheses that compared to IVF cycles undergoing preimplantation genetic testing for aneuploidy (PGT-A) with or without testing for monogenic disorders (PGT-M), IVF cycles undergoing PGT for structural rearrangements (PGT-SR) will have (1) a poorer blastocyst conversion rate and (2) fewer usable blastocysts available for transfer. Secondarily, the study aimed to compare pregnancy outcomes among PGT groups. Retrospective cohort study including cycles started from January 1, 2012, to March 30, 2020, with the intent of pursuing PGT-A, PGT-A with PGT-M, and PGT-SR, with trophectoderm biopsy on days 5 or 6. A total of 658 women underwent 902 cycles, including 607 PGT-A, 216 PGT-A&M, and 79 PGT-SR cycles. When compared with the blastocyst conversion rate for the PGT-A group (59.4%), and after adjustment for patient age, total number of mature oocytes, BMI, and ICSI, there were no significant differences for either the PGT-A&M (69.7%, aRR 1.03, 95% CI 0.96-1.10) or PGT-SR (63.2%, aRR1.04, 95% CI 0.96-1.13) groups. Compared to the PGT-A group, the proportion of usable blastocysts was statistically significantly lower in the PGT-SR group: 35.1% versus 24.4% (aRR 0.57, 95% CI 0.46-0.71) and the PGT-A&M group: 35.1% versus 31.5% (aRR 0.68, 95% CI 0.58-0.81). Implantation, pregnancy, and miscarriage rates were equivalent for all groups. Patients with structural rearrangements have similar blastocyst development but significantly fewer usable blastocysts available for transfer compared to PGT-A testers. Nevertheless, with the transfer of a usable embryo, PGT-SR testers perform as well as those testing for PGT-A.

In-vitro maturation of oocytes recovered during cryopreservation of pre-pubertal girls undergoing fertility preservation

Research questionIn-vitro maturation (IVM) of oocytes recovered during ovarian tissue cryopreservation (OTC) is often practised, although it is still considered experimental. To date, only a few studies have examined the success of this maturation process in pre-menarche girls. The aim of this study was to examine the outcomes of IVM of oocytes recovered during OTC in pre-menarche patients scheduled for onco-therapy. DesignA retrospective cohort study in a tertiary university-affiliated hospital. A total of 93 patients aged 0–25 years who underwent OTC as part of onco-fertility preservation between 2007 and 2019 were included in the study. Oocytes were recovered from the medium after OTC and matured over 48 h. Oocyte development and maturation rate were recorded and compared between different age groups. ResultsPatient's age was not correlated linearly with the total number of mature oocytes R = 0.2. The absolute maturation rate in post-menarche and pre-menarche patients differed significantly (38.0% versus 25.3%, respectively; P > 0.001), whereas the degeneration rate of the oocytes did not (39.8% versus 33.5%; P = 0.167). The pre-menarche group had significantly lower mean number of metaphase II oocytes compared with the post-menarche group (2.8 [±2.3] versus 5.6 [±4.6]; P = 0.01; 95% CI –4.62 to –0.46). Oocytes recovered from patients aged 1–5 years demonstrated low maturation rate. ConclusionsOocytes recovered from pre-menarche girls, and especially those younger than the age of 5 years who undergo fertility preservation, have a lower chance of reaching maturity in IVM compared with older women. This may indicate a need for alternative methods for preserving fertility in these young patients.

Priming Before In Vitro Maturation Cycles in Cancer Patients Undergoing Urgent Fertility Preservation: a Randomized Controlled Study

In vitro maturation (IVM) of oocytes retrieved at germinal vesicle stage, followed by vitrification of mature oocytes, has emerged as a fertility preservation (FP) option. This technique was first developed for patients with polycystic ovarian syndrome. In this population, providing LH activity prior to oocyte collection has been associated with better IVM outcomes. However, the benefit of this treatment in normo-ovulatory breast cancer (BC) patients undergoing IVM for FP purpose has never been investigated. To assess if the absence of therapeutic intervention prior to oocyte retrieval for IVM modifies IVM outcomes in BC patients undergoing urgent FP, we performed a non-inferiority, randomized controlled trial. The main outcome was the total number of mature oocytes obtained and cryopreserved after IVM. A total of 172 normo-ovulatory women, suffering from BC, 18 to 39years of age received no injection or a subcutaneous injection of hCG or GnRH agonist (GnRHa) 36h before oocytes retrieval according to randomized allocation. The total number of cryopreserved oocytes were 5.1 ± 3.8, 5.4 ± 3.8, and 6.0 ± 4.2 oocytes, respectively in the without, hCG and GnRHa groups. Mean differences were not significant between the three groups (- 0.5; CI 97.5% [- 2.03:1.02] and - 0.22; CI 97.5% [- 1.75:1.32], respectively). Intention to treat analyses failed to show non-inferiority in the "without injection group" in comparison with hCG or GnRHa groups. Our results are not conclusive enough to modify our practices and to stop administering hCG or GnRHa before IVM cycles for FP. The study was retrospectively registered to clinical trial (ID NCT03954197) in May 2019.

Dydrogesterone-primed ovarian stimulation is an effective alternative to gonadotropin-releasing hormone antagonist protocol for freeze-all cycles in polycystic ovary syndrome.

To compare the effects of progestin-primed ovarian stimulation using dydrogesterone (DYD) and a gonadotropin-releasing hormone (GnRH) antagonist protocol on cycle characteristics and pregnancy rates in freeze-all cycles in patients with polycystic ovary syndrome (PCOS). Medical records of PCOS patients who underwent freeze-all in vitro fertilization cycles between April 2017 and April 2019 at the Novafertil in vitro fertilization Center were retrospectively evaluated. The primary outcome measure was the incidence of premature luteinizing hormone surge. Secondary outcome measures were the total number of mature oocytes retrieved, fertilization rate, clinical pregnancy rates and ongoing pregnancy rates. A total of 525 patients were included in the study. DYD-primed ovarian stimulation and a GnRH antagonist protocol were applied in 258 and 267 patients, respectively. The baseline parameters were similar between the two groups. The numbers of mature and fertilized oocytes were similar in the cetrorelix (CET) group and DYD group (11.43 ± 3.48 vs. 11.29 ± 4.34, respectively, P = 0.692; and 8.98 ± 2.93 vs. 8.62 ± 3.67, respectively, P = 0.208). Premature luteinization was rare in both groups, and the difference between the groups was not statistically significant (2.9% vs. 1.5%, respectively, P = 0.268). There was no significant difference in clinical pregnancy rate of the first frozen embryo transfer cycle between the DYG group and the CET group (56% [120/214] vs. 55.6% [113/203], respectively, P = 0.283). There were no significant differences in biochemical pregnancy rates, implantation rates, miscarriage rates or ongoing pregnancy rates between the two groups (P > 0.05). Dydrogesterone-primed ovarian stimulation seems to be an effective alternative to the GnRH antagonist protocol for freeze-all cycles in PCOS patients.

Outcomes of ovarian stimulation and fertility preservation in breast cancer patients with different hormonal receptor profiles.

To evaluate fertility preservation outcomes in breast cancer women with different hormonal receptor profiles before oncological treatment. The study population included women with a diagnosis of breast cancer who underwent fertility preservation from 2009 until 2018 at a university-affiliated tertiary hospital. Stimulation parameters and fertility preservation outcomes were compared among the following receptor-specific profile groups: (1) estrogen receptor positive (ER+) versus estrogen receptor negative (ER-), (2) triple-negative breast cancer (TNBC) versus estrogen and progesterone receptor positive (ER+/PR+), and (3) TNBC versus non-TNBC. Primary outcome was the total number of mature oocytes. Secondary outcomes included the number of retrieved oocytes, the peak estradiol level, and the number of follicles > 14mm on the final oocyte maturation trigger day. A total of 155 cycles were included in the final analysis. These were divided into the exposure groups of ER+ (n = 97), ER- (n = 58), ER+/PR+ (n = 85), TNBC (n = 57), and non-TNBC (n = 98). Cycle outcomes revealed similar number of retrieved oocytes and follicles > 14mm on the trigger day. Women with TNBC had significantly lower number of mature oocytes compared with those with ER + PR+ (7 (5-11) versus 9 (7-15); p = 0.02) and non-TNBC (7 (5-11) versus 9 (7-16); p = 0.01) status. Triple-negative breast cancer profile was associated with a significant reduction in the chance of developing over 10 mature oocytes (OR 0.41; 95% CI 0.19-0.92). Among the different hormonal receptor profiles in breast cancer, the TNBC subtype has a negative effect on fertility preservation outcomes.

Influence of stage and grade of breast cancer on fertility preservation outcome in reproductive-aged women.

Does breast cancer spread and aggressiveness affect fertility-preservation results? Retrospective cohort study of women with breast cancer undergoing fertility-preservation treatment. age 18-38 years and use of gonadotrophin releasing hormone antagonist protocol; exclusion criteria: recurrent cancer, previous oncological treatment, previous ovarian surgery and known ovarian pathology. Stimulation cycle outcomes of women with low-stage breast cancer were compared with those with high-stage disease. Patients with low-grade (G1-2) were compared with those with high-grade (G3) malignancies. total number of mature oocytes; secondary outcomes: oestradiol level and number of follicles wider than 14 mm on the day of trigger, number of retrieved oocytes and cryopreserved embryos. The final analysis included 155 patients. Patients with high-grade tumours (n = 80; age 32 years [28-35]) had significantly lower number of mature oocytes compared with patients with low-grade cancer (n = 75; age 32 years [28-35]; seven mature oocytes [4-10] versus 13 mature oocytes [7-17]; P = 0.0002). The number of cryopreserved embryos was also lower in the high-grade group (three [2-5] versus five [3-9]; P = 0.02). Stage-based analysis revealed a similar number of mature oocytes in high-stage (n = 73; age 32 years [28-35]) compared with low-stage group (n = 82; age 33 years [28-35]; eight mature oocytes [4-13] versus nine mature oocytes [7-15]; P = 0.06). High-grade breast cancer has a negative effect on total number of mature oocytes and cryopreserved embryos.

Is oocyte maturity influenced by ovulation trigger type in oocyte donation cycles?

The aim of this study was to compare clinical and laboratory outcomes between GnRHa, dual and HCG triggers in altruistic oocyte donation cycles. Normal or high responders were given either gonadotropin releasing hormone agonist (GnRHa) or a dual trigger of GnRHa and a low dose of human chorionic gonadotropin (HCG). Low responders were given HCG trigger. In 333 cycles, 232 (69.7%) received GnRHa trigger, 59 (17.7%) received dual trigger and 42 (12.6%) had HCG trigger. The total number of mature oocytes retrieved and cryopreserved were significantly higher in the GnRHa and dual trigger groups, compared to the HCG group (p < 0.001). However, the ovarian hyperstimulation syndrome (OHSS) rate was significantly higher in the dual trigger group (n = 5 (8.5%)), compared to the GnRH agonist (n = 1 (0.4%)) and HCG groups (n = 0 (0%)) (p = 0.001). GnRHa trigger maximises mature oocyte yields in oocyte donors suspected of normal and high response but offers a significant reduction in OHSS risk compared to dual trigger. As such, dual trigger should not be used in oocyte donation. HCG trigger can also be used with a very low risk of OHSS at low risk of OHSS in carefully selected donors where GnRHa is unlikely to be effective.

Fertility preservation in Turner syndrome: Karyotype does not predict ovarian response to stimulation

Turner syndrome (TS) is responsible for gonadal dysgenesis with high risk of premature ovarian insufficiency. Little is known about fertility preservation (FP) strategies is this population. Data from women with TS consulting with a fertility specialist in our FP centre from 2014 to 2018 were retrospectively collected. Total number of mature oocytes cryopreserved using vitrification. Nine women with TS were referred. Three women with different karyotypes underwent controlled ovarian stimulation (COS) for oocyte vitrification. Mean age at TS diagnosis was 13.7years [9-20]. Mean referral delay between TS diagnosis and fertility consultation was 9.7years [7-14]. First counselling for FP was provided at 23.7years [18-28]. Mean AMH serum level prior to COS was 53.8pmol/L [3.6-95]. All three women succeeded in obtaining cryopreserved oocytes with a mean number of 15.3 per woman [9-20] and 9.2 per COS cycle [2-20]. Ovarian response to COS was unexpectedly remarkable for the woman with a complete 45,X monosomy. Procedure was well tolerated for all women. None of them have used oocytes for in vitro fertilization yet. Independently of karyotype, antral follicular count, AMH and FSH levels seemed to be reliable predictive markers of oocyte cryopreservation success. In a monosomic TS woman, cryptic ovarian mosaicism could explain a successful ovarian response to stimulation with a high number of retrieved oocytes. In case of spontaneous menarche, TS adolescents should be referred during transition to adulthood for FP counselling to avoid referral delay and limit time-related diminished ovarian reserve.

Blastocyst conversion rate and ploidy in translocation carriers

To determine if women intending to undergo in vitro fertilization (IVF) with preimplantation genetic testing for structural rearrangements (PGT-SR) have a poorer rate of blastocyst conversion and an increased risk of aneuploidy compared to patients undergoing IVF with PGT-A (PGT for aneuploidy). Retrospective cohort study. Autologous cycles with the intent of pursuing PGT-A or PGT-SR with biopsy on either day 5 or 6 were identified from all IVF cycles performed in our program from 1/2012 to 10/2018. Outcome variables assessed included fertilization rate (%2PN/MII), blastocyst conversion rate (% total blastocysts/2PN), proportion of biopsiable blastocysts (% blastocysts of adequate quality for biopsy on days 5 or 6/total blastocysts), % euploid embryos, and % embryos with inconclusive biopsy results. GEE modeling was used to control for patients with more than one cycle during the study period. Rate ratios (RR) were calculated using a Poisson regression with offset model with PGT-A cycles as the referent group, adjusted for patient age, total number of mature oocytes, BMI and intracytoplasmic sperm injection (ICSI). 566 cycles from 388 patients were included (462 PGT-A and 104 PGT-SR cycles). Demographic information and cycle characteristics were similar between groups in terms of age, AMH, and day 3 FSH, with small differences in BMI and use of ICSI. The laboratory outcome data are shown in the Table 1. Blastocyst conversion rate was statistically significantly higher in the PGT-SR group, although there was no difference between groups in the percentage of blastocysts biopsied on either day 5 or day 6, or the percentage of biopsies that were noninformative. Of note, in the PGT-A group, 42% of biopsied embryos were euploid, compared to only 29% in the PGT-SR group (aRR 0.86; 95% CI 0.73-1.00). Although translocation carriers have superior blastocyst development and a similar percentage of embryos available for biopsy compared to PGT-A testers, this group had fewer euploid blastocysts available for transfer. These findings should be helpful in counseling patients with structural rearrangements.Table 1Comparison of laboratory outcomes and ploidy results following blastocyst biopsy for patients using PGT-A versus PGT-SRVariablePGT-AMean ± SDPGT-SRMean ± SDaRR (95% CI)Referent: PGT-A% 2PN/MII82% ± 1880% ± 201.02 (0.98-1.06)% Blastocysts/2PN66% ± 2472% ± 221.07 (1.01-1.13)% D5 Biopsied/Total blastocysts67% ± 3069% ± 271.08 (1.00-1.18)% D6 Biopsied/Total blastocysts46% ± 3338% ± 300.79 (0.65-0.96)% Euploid blastocysts42% ± 3329% ± 230.86 (0.73-1.00)% Blastocysts with no result4% ± 132% ± 50.70 (0.39-1.26) Open table in a new tab