Is infertility more common among patients with multiple sclerosis? Implications for utilization of assisted reproductive techniques.

RESEARCH QUESTION: Is fertility affected in women with multiple sclerosis (MS), and what is their usage of assisted reproductive technology (ART)? DESIGN: Data regarding multiple sclerosis and ART usage among patients with multiple sclerosis were extracted from the Israeli health maintenance organization Clalit Health Service database. Data regarding the diagnosis and treatment of multiple sclerosis, cause of infertility and use of fertility treatments were collected for all female multiple sclerosis patients aged 18-45 years between 2005 and 2021. Each patient was matched by age in a 1:10 ratio with reference women from the general population. The prevalence of infertility was compared between the two groups. Univariate and multivariate statistical tests were used to analyse the association between multiple sclerosis and fertility treatments including IVF and ovarian stimulation. RESULTS: During the study period, 1309 multiple sclerosis patients were compared with 13,090 controls from the general population matched for age. The mean age was 29 ± 7.8 years. The overall prevalence of infertility was 15.4% (202/1309) among the multiple sclerosis patients, similar to the general population (16.3%; 2129/13090) (P = 0.436). The prevalence of IVF and ovarian stimulation was similar among multiple sclerosis patients and matched controls from the general population (8.1% versus 7.2%, P = 0.240; 13.8% versus 14.3%; P = 0.624, respectively). CONCLUSIONS: The results show similar rates of infertility and fertility treatments among multiple sclerosis patients and the general population. This provides reassurance that fertility among women with multiple sclerosis does not differ from that of women in the general population, and indicates there is no excessive usage of ART.

Attitude of BRCA1/2 mutation carriers towards fertility preservation, family planning and preimplantation genetic testing for primary prevention of breast and ovarian cancer in the next generation.

PURPOSE: To study the attitude of BRCA1/2 mutation carriers regarding family planning, fertility preservation, and preimplantation genetic testing (PGT). METHODS: A national cross-sectional study was conducted by the distribution of an anonymous questionnaire, from August 2022 to January 2023. The main outcomes measures were discussion, acceptance, and performance rates of fertility preservation and PGT. RESULTS: The questionnaire was completed by 530 BRCA1/2 mutation carriers. The mean (SD) age at mutation detection was 36.4 (9.6) years. At the time of mutation detection, 40% did not have children. Following mutation detection, 37% of responders changed their family planning, mostly choosing to have children earlier or to have less children than planned. Twenty-eight percent of BRCA carriers discussed the option of fertility preservation with a physician, 72% agreed that fertility preservation is an acceptable option for BRCA1/2 mutation carriers and finally 11% underwent oocyte/embryo vitrification before RRBSO. 44% of BRCA carriers discussed the option of PGT, 58% agreed that PGT is justified in BRCA1/2 mutation carriers and finally 8% underwent PGT to select non-carrier embryos. In a multivariate analysis, age under 35 years and the a priori need for fertility treatments were both found significant factors increasing the likelihood of performing fertility preservation and PGT. CONCLUSION: This study emphasizes that despite a substantial proportion of women admitting that mutation detection affected their family planning and high acceptance rates, performance of fertility preservation and PGT remained exceedingly low. Increasing the knowledge and awareness of these issues is important and should be included in multidisciplinary counselling.

Evaluation of fragmented embryos implantation potential using time-lapse technology.

AIM: To examine the implantation potential of fragmented embryos that underwent morphokinetic evaluation in a time-lapse incubator. METHODS: A retrospective study analyzing 4210 Day 5 embryos which were incubated in a time-lapse incubator, between 2013 and 2019. Embryos with more than 5% fragmentation (379 embryos) were included in the study. Embryos selected using the general model and re-examined by our in-house model. Embryo fragmentation percentage was documented from the first cell-division (start fragmentation) to its maximal percentage (final fragmentation), and the ratio between them (fragmentation worsening). Data were analyzed with relation to embryo development, embryos transfer or freezing, clinical pregnancy, and live birth rates. RESULTS: Embryo fragmentation and morphokinetics were found to be independent variables for clinical pregnancy achievements. A higher fragmentation worsening was noted among discarded embryos compared to transferred or frozen embryos (p < 0.0001). Advanced maternal age had a significant negative effect on fragmentation (p < 0.001). Missed abortion rates were similar in fragmented embryos that implanted compared with the overall population. Live birth rates were comparable among embryos which were selected for transfer or freezing by their morphokinetics and had different severity of fragmentation. CONCLUSION: Our study shows that fragmented embryos have a potential to implant and therefore should be selected for transfer. Laboratories which do not use time-lapse incubators for embryo selection, should consider transferring fragmented embryos, since they have an acceptable chance for live birth. Calculation of fragmentation worsening may enhance our ability to predict embryo development. Further research with analysis of more fragmented embryo maybe beneficial. This study was approved by the local ethics committee No. 0010-19 CMC on April 18th, 2019.

Effect of the co-administration of HCG and GnRH agonist (dual trigger) versus standard HCG trigger on morphokinetic embryo parameters.

RESEARCH QUESTION: Does dual trigger (the co-administration of triptorelin 0.2 mg and recombinant human chorionic gonadotrophin (HCG) [Decapeptyl 0.2 mg + Ovitrelle 250 µg]) versus standard recombinant HCG (Ovitrelle 250 µg) affect embryo quality and morphokinetic parameters? DESIGN: Morphokinetic parameters and embryo quality of embryos derived from the first gonadotrophin-releasing hormone (GnRH) antagonist IVF/intracytoplasmic sperm injection (ICSI) cycles triggered by dual trigger or standard HCG trigger in women ≤42 years. Outcome measures included time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second cycle (s2), duration of the second cycle (cc2) and known implantation data (KID) scoring for embryo quality. Multivariate linear and logistic regression analyses were performed for confounding factors. RESULTS: A total of 4859 embryos were analysed: 1803 embryos from 267 cycles in the dual trigger group and 3056 embryos from 463 cycles in the HCG trigger group. The groups were similar in patient and treatment characteristics apart from a higher maternal body mass index and lower maturation rate in the dual trigger group. Time to second polar body extrusion was shorter in the dual trigger group. Cleavage timings from zygote to an 8-cell embryo did not differ between the two groups. There was a higher percentage of embryos with an optimal cc2 duration in the HCG group. In multivariate logistic regression models, the trigger type was not a significant factor for cell cycle division parameters. CONCLUSIONS: Overall, there was no significant difference in the morphokinetic parameters or quality of embryos evaluated using a time-lapse monitoring system between embryos derived following dual trigger compared with HCG.

Complications of the third stage of labor are more prevalent in IVF pregnancies.

BACKGROUND: Pregnancies conceived by in vitro fertilization (IVF) are associated with a higher prevalence of perinatal complications than pregnancies conceived spontaneously, even after correction of confounding factors. Little is known about the prevalence of complications of the third stage of labor in IVF pregnancies. OBJECTIVE: To compare the prevalence and types of complications of the third stage of labor following vaginal delivery of singleton infants born to matched groups of women who conceived through IVF or spontaneously. STUDY DESIGN: A retrospective case-control study design was used. The electronic delivery files of a tertiary medical center were reviewed for all women with a singleton IVF pregnancy who gave birth by vaginal delivery from August 2011 to March 2014. The women were matched 1:2 for age, gravidity, parity, and week of delivery to women with a singleton spontaneously conceived pregnancy who gave birth by vaginal delivery during the same period at the same hospital. The impact of mode of conception on the length and complications of the third stage of labor was evaluated. RESULTS: The study group consisted of 242 women with IVF pregnancies (cases), and 484 matched controls with spontaneously conceived pregnancies (controls). The length of the third stage was similar in the cases and controls (14.23 ± 8.89 and 13.69 ± 9.19 min, respectively). IVF pregnancy was associated with a significantly higher rate of postpartum hemorrhage (PPH) (5.79 versus 1.45%, p = .001), manual removal of retained placenta (11.98 versus 7.02%, p = .025), and blood transfusion (2.07 versus 0.41%, p = .032). On multivariate analysis, pregnancy conceived by IVF was an independent risk factor for an adverse outcome of the third stage of labor (OR 2.86, 95% CI 1.53-5.33). CONCLUSION: After correction for confounders, IVF conception proved to be a significant independent risk factor for PPH, manual removal of the placenta, and blood transfusion in the third stage of labor. Therefore, the management of women who give birth vaginally following IVF pregnancy should be designed to anticipate complications in the third stage even in the absence of other risk factors.

Does the outcome of fresh embryo transfer affect the outcome of subsequent thawed embryo transfers from sibling oocytes in patients that utilized all their embryos?

The association between fresh embryo transfer (ET) outcome and the subsequent frozen-thawed (FET) cycles that follow is not clear, mainly because of incomplete embryo cohort utilization. The aim of this study was to determine if the outcome of a fresh ET affects the frozen cumulative clinical pregnancy (CP) and live birth (LB) rates resulting from the utilization of all surplus embryos from sibling oocytes. Outcome measures were the FET cumulative CP and LB rates. Multivariate logistic regression was performed for the frozen cumulative CP rate and adjusted for age, the number of oocytes, fresh ET outcome and other confounders. A total of 1313 cycles met the inclusion criteria. The FET cumulative CP and LB rates were not affected by the outcome of the fresh ET. The FET cumulative CP rate increased with the number of oocytes collected regardless of whether a pregnancy was achieved in the fresh cycle or not. In multivariate analysis, age (OR = 0.96, 95% CI 0.94-0.98), protocol (OR = 0.13, 95% CI 0.03-0.57) and the number of oocytes (OR = 1.05, 95% CI 1.02-1.07) were associated with the frozen cumulative CP rate. It is concluded that fresh ET does not impact the outcome of the vitrified-thawed embryos from the same oocyte cohort.

Long-term ovarian reserve and fertility outcomes in female survivors of childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, yet data regarding long-term ovarian reserve of female survivors are limited. The aim of this study was to investigate whether there is a differential pattern of anti-Mullerian hormone (AMH) levels in female childhood ALL survivors compared with the normal age-matched population. In a cohort of 56 female childhood ALL survivors (median age 29 years; median follow-up 20.6 years), a negative correlation was found between age at leukemia diagnosis and age-adjusted anti-Mullerian hormone (AMH) levels (r = -0.334, p = .031). Despite alkylating agent therapy, AMH levels did not differ significantly from age-related nomograms (age < 30, p = .17; age ≥ 30, p = .94). The mean number of children per fertile woman adjusted for maternal age was similar to the national average (2.76 versus 3.11, p = .19). Our results imply that reproductive outcomes are not significantly hampered in female pediatric ALL survivors. Long-term surveillance of ovarian reserve may enable personalized survivorship counseling.

A matched propensity score study of embryo morphokinetics following gonadotropin-releasing hormone agonist versus human chorionic gonadotropin trigger.

PURPOSE: To compare morphokinetic parameters and quality of embryos derived from GnRH antagonist ICSI cycles triggered either with GnRH agonist or standard hCG between matched groups of patients. METHODS: Morphokinetic parameters of embryos derived from matched first GnRH antagonist ICSI cycles triggered by GnRH agonist or standard hCG between 2013 and 2016 were compared. Matching was performed for maternal age, peak estradiol levels, and number of oocytes retrieved. Outcome measures were: time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second and third cycles (S2 and S3), duration of the second and third cycle (CC2 and CC3), optimal cell cycle division parameters, and known implantation data (KID) scoring for embryo quality. Multivariate linear and logistic regression analyses were performed for confounding factors. RESULTS: We analyzed 824 embryos from 84 GnRH agonist trigger cycles and 746 embryos from 84 matched hCG trigger cycles. Embryos derived from the cycles triggered with hCG triggering cleaved faster than those deriving from GnRH agonist trigger. The differences were significant throughout most stages of embryo development (t3-t6), and a shorter second cell cycle duration of the hCG trigger embryos was observed. There was no difference in synchrony of the second and third cell cycles and the optimal cell cycle division parameters between the two groups, but there was a higher percentage of embryos without multinucleation in the hCG trigger group (27.8% vs. 21.6%, p < 0.001). CONCLUSION: The type of trigger in matched antagonist ICSI cycles was found to affect early embryo cleavage times but not embryo quality.

Pregnancy outcome following fetal reduction from dichorionic twins to singleton gestation.

BACKGROUND: There are still some controversies regarding the risks and benefits of fetal reduction from twins to singletons. We aimed to evaluate if fetal reduction from twins to singleton improves pregnancy outcome. METHODS: Retrospective analysis of all dichorionic-diamniotic twin pregnancies, who underwent fetal reduction. Pregnancy outcome was compared to ongoing, non-reduced, dichorionic-diamniotic gestations. Primary outcome was preterm birth prior to 37 gestational weeks. Secondary outcomes included: preterm birth prior to 34 gestational weeks, gestational age at delivery, birthweight, small for gestational age, hypertensive disorders, gestational diabetes and stillbirth. RESULTS: Ninety-eight reduced pregnancies were compared with 222 ongoing twins. Preterm birth < 37 gestational weeks (39.6% vs. 57.6%, p < 0.001) was significantly lower in the reduced group compared to the ongoing twins' group. A multivariate analysis, controlling for parity and mode of conception, demonstrated that fetal reduction independently and significantly reduced the risk for prematurity (aOR 0.495, 95% CI -0.299-0.819). Subgroup analysis, similarly adjusted demonstrated lower rates of preterm delivery in those undergoing elective reduction (aOR = 0.206, 95% CI 0.065-0.651), reduction due to fetal anomalies (aOR = 0.522, 95% CI 0.295-0.926) and 1st trimester reduction (aOR = 0.297, 95% Cl 0.131-0.674) all compared to ongoing twins. A Kaplan-Meier survival curve showed a significant proportion of non-delivered women at each gestational week in the reduced group compared to non-reduced twins, after 29 gestational weeks. CONCLUSIONS: Fetal reduction from twins to singleton reduces the risk of preterm birth < 37 gestational weeks, but not for more severe maternal and perinatal complications.

The entire range of trigger-day endometrial thickness in fresh IVF cycles is independently correlated with live birth rate.

RESEARCH QUESTION: What is the association of the entire range of trigger-day endometrial thickness (EMT) with live birth rate (LBR) after IVF and fresh embryo transfer? Although EMT is amenable to convenient non-invasive routine measurement, studies of the association between pre-trigger EMT and assisted reproductive technology outcome have yielded equivocal results. DESIGN: A cohort of IVF fresh day-3 embryo transfers in patients aged 42 years and younger in a single centre between 2009 and 2017. The LBR was calculated for all trigger-day EMT values, stratified into five groups overall and within subgroups of patient age and ovarian response. Univariate analysis and multivariate logistic regression models were used to compare the LBRs at different EMT measurements adjusting for various independent variables. RESULTS: A total of 5133 cycles were included. The LBRs were as follows: 11.22% (35/312) in cycles with EMT 6 mm or less, 17.98% (380/2114) in cycles with EMT 7-9 mm, 23.44% (476/2031) in cycles with EMT 10-12 mm, 25.62% (144/562) in cycles with EMT 13-15 mm and 34.21% (39/114) in cycles with EMT 16 mm or more (P < 0.001). Similar findings were observed by patient age and ovarian response. The observation was confirmed by multivariate logistic regression analysis in which the EMT was found to be a significant independent predictor of LBR even after controlling for various confounders (OR 0.935, 95% CI 0.908 to 0.962; P < 0.001). CONCLUSIONS: Pre-trigger EMT is in significant independent correlation with LBR, even after adjusting for age and ovarian response. Maximal endometrial proliferation is beneficial, and fresh embryo transfer can be carried out at high EMT values without endangering the outcome of the cycle.

The association between treatment parameters on the day of gonadotropin-releasing hormone antagonist initiation during a flexible protocol and oocyte maturation rate.

This study aimed to evaluate the effects of different treatment parameters on the day of GnRH antagonist initiation on oocyte maturation rate. We performed a retrospective cohort study of women aged ≤ 38 who underwent their first IVF-ICSI treatment using a flexible GnRH antagonist protocol in a single university-affiliated medical center during 2005-2015. Treatment parameters of three groups of oocyte maturation rates (<60%, 60-90%,>90%) were compared. Multivariate analysis was conducted to detect an association between treatment parameters on the day of GnRH antagonist initiation and oocyte maturation rate. The cohort included 458 patients, of whom 180 (39%) had a high oocyte maturation rate (≥90%), 211 (46%) had an oocyte maturation rate between 60-90% and 67 (15%) had a low maturation rate (≤60%). Women with a high maturation rate had longer duration of treatment (10.3 ± 2.9 days vs. 9.6 ± 2.5 vs. 9.5 ± 3.2, P = 0.019), lower levels of estradiol (1985 ± 1357 vs. 2406 ± 1666 vs. 2325 ± 1811, P = 0.027) and lower estradiol/maximal follicular diameter ratio on the day of GnRH antagonist initiation (137 ± 89 vs. 165 ± 103 vs. 163 ± 125, P = 0.019) as compared to women with medium and low maturation rates, respectively. Using linear regression multivariate analysis, lower estradiol and lower estradiol/maximal follicular diameter ratio on GnRH antagonist initiation day were associated with higher oocyte maturation rate. Further prospective studies to determine the best timing for GnRH antagonist initiation are needed.

Use of Simvastatin, Fibrin Clots, and Their Combination to Improve Human Ovarian Tissue Grafting for Fertility Restoration After Anti-Cancer Therapy.

Anticancer treatments, particularly chemotherapy, induce ovarian damage and loss of ovarian follicles. There are limited options for fertility restoration, one of which is pre-chemotherapy cryopreservation of ovarian tissue. Transplantation of frozen-thawed human ovarian tissue from cancer survivors has resulted in live-births. There is extensive follicular loss immediately after grafting, probably due to too slow graft revascularization. To avoid this problem, it is important to develop methods to improve ovarian tissue neovascularization. The study's purpose was to investigate if treatment of murine hosts with simvastatin or/and embedding human ovarian tissue within fibrin clots can improve human ovarian tissue grafting (simvastatin and fibrin clots promote vascularization). There was a significantly higher number of follicles in group A (ungrafted control) than in group B (untreated tissue). Group C (simvastatin-treated hosts) had the highest levels of follicle atresia. Group C had significantly more proliferating follicles (Ki67-stained) than groups B and E (simvastatin-treated hosts and tissue embedded within fibrin clots), group D (tissue embedded within fibrin clots) had significantly more proliferating follicles (Ki67-stained) than group B. On immunofluorescence study, only groups D and E showed vascular structures that expressed both human and murine markers (mouse-specific platelet endothelial cell adhesion molecule, PECAM, and human-specific von Willebrand factor, vWF). Peripheral human vWF expression was significantly higher in group E than group B. Diffuse human vWF expression was significantly higher in groups A and E than groups B and C. When grafts were not embedded in fibrin, there was a significant loss of human vWF expression compared to groups A and E. This protocol may be tested to improve ovarian implantation in cancer survivors.

Does 'Dual Trigger' Increase Oocyte Maturation Rate?

The aim of this study was to evaluate the oocyte maturation rate when GnRH-a and hCG (dual trigger) are co-administered, compared to the standard hCG trigger within the same patient. Included in the study were GnRH antagonist ICSI cycles performed in 137 patients who had a standard hCG trigger cycle and a dual trigger cycle between 1/1/2013 and 31/12/2017. The mean patient age (35.9 ± 5.6 and 35.2 ± 5.9; <0.001), FSH dose (4140 ± 2065 and 3585 ± 1858; <0.01), number of retrieved oocytes (10.3 ± 6.2 and 8.9 ± 6.1; 0.011) were higher in the dual trigger group compared to the hCG trigger group, oocyte maturation rate was identical. Maturation rate following dual trigger was significantly higher among 34 patients who had a maturation rate of <70% following hCG triggering and among 16 patients with a maturation rate <50% rate following hCG trigger (54% vs. 74%, p < .001 and 44% vs. 73%, p = .006; respectively). In conclusion, co-administration of GnRH agonist and hCG for final oocyte maturation substantially increased the oocyte maturation rate in patients with low oocyte maturation rate in their hCG triggered cycle, but not in an unselected population of patients.IMPACT STATEMENTWhat is already known on this subject? The co-administration of GnRH agonist and hCG for final oocyte maturation prior to oocyte retrieval may improve IVF outcome in patients with a high proportion of immature oocytes. The few studies on dual trigger in patients with a high proportion of immature oocytes or in normal responders have shown conflicting results.What do the results of this study add? We found that co-administration of GnRH agonist and hCG for final oocyte maturation substantially increased the oocyte maturation rate in patients with low oocyte maturation rate in their hCG triggered cycle, but not in an unselected population of patients.What are the implications of these findings for clinical practice and/or further research? The results of this study implicate that in selected population with low oocyte maturation rate, there is an advantage in using dual trigger. However, larger prospective trials are warranted to better assess oocyte response in dual trigger.

Perinatal outcome following induction of labor in patients with good glycemic controlled gestational diabetes: does timing matter?

PURPOSE: To compare maternal and neonatal outcomes in women with good glycemic controlled gestational diabetes mellitus (GDM) undergoing induction of labor at early and late term. METHODS: A retrospective cohort study of all women with singleton pregnancies and well-controlled GDM undergoing induction of labor for non-GDM indications in the early (37 + 0-38 + 6 gestational weeks) and late term (39 + 0-40 + 6 weeks), in a single university-affiliated medical center (2014-2016). Exclusion criteria included: pre-gestational diabetes, multiple gestations and elective cesarean delivery. Maternal and neonatal outcomes were compared between groups. Composite maternal outcome included: post-partum hemorrhage, blood products transfusion, and cesarean or instrumental delivery. Composite neonatal outcome included: neonatal intensive care unit admission, respiratory distress syndrome, hypoglycemia and jaundice. RESULTS: Overall, 430 women met inclusion criteria. Amongst them, 193 (44.88%) were induced at early term and 237 (55.11%) were induced at late term. There were higher rates of hypertensive complications of any kind and pre-eclampsia, in women induced at early term (11.04% vs. 4.26%, p = 0.021, and 5.92% vs. 1.60%, p = 0.04, respectively). There were no differences in maternal and neonatal outcomes between groups. Rates of composite maternal outcome and composite neonatal outcome did not differ between groups (OR 0.92, 95% CI 0.59-1.44, p = 0.73 and OR 0.78, 95% CI 0.47-1.3, p = 0.36, respectively). CONCLUSION: Women with good glycemic controlled GDM may be safely induced at early term, when other indications exist, without an increased risk for adverse maternal or neonatal outcomes.

Perinatal outcome in gestational diabetes according to different diagnostic criteria.

Objectives To evaluate whether gestational diabetes mellitus (GDM) diagnosed by different criteria impacts perinatal outcome. Methods This was a retrospective study of deliveries with a diagnosis of GDM (2014-2016). Perinatal outcomes were compared between patients with: (1) GDM diagnosed according to a single abnormal value on the 100-g oral glucose tolerance test (OGTT); (2) two or more abnormal OGTT values; and (3) a 50-g glucose challenge test (GCT) value ≥200 mg/dL. Results A total of 1163 women met the inclusion criteria, of whom 441 (37.9%) were diagnosed according to a single abnormal OGTT value, 627 (53.9%) had two or more abnormal OGTT values and 95 (8.17%) had a GCT value ≥200 mg/dL. Diet-only treatment was significantly higher in the single abnormal value group (70.3% vs. 65.1% vs. 50.5%) and rates of medical treatment were significantly higher in the GCT ≥ 200 mg/dL group (P < 0.05). Women in the GCT ≥ 200 mg/dL group had higher rates of neonatal intensive care unit (NICU) admission (10.5% vs. 2.7% vs. 2.8%, P < 0.001) and neonatal hypoglycemia (5.3% vs. 0.5% vs. 0.8%, P < 0.001). On multivariate logistic regression, GCT ≥ 200 mg/dL was no longer associated with higher rates of NICU admission and neonatal hypoglycemia (P > 0.05). Conclusion No difference was noted in the perinatal outcome amongst the different methods used for diagnosing GDM.

Effect of letrozole added to gonadotropins in controlled ovarian stimulation protocols on the yield and maturity of retrieved oocytes.

We aimed to evaluate the effect of co-administration of letrozole and gonadotropins during ovarian stimulation on oocyte yield and maturation in breast cancer patients prior to chemotherapy. A retrospective cohort design was used comparing oocyte cryopreservation cycles among patients with breast cancer patients with other oncological indications and women undergoing elective oocyte cryopreservation. All patients were treated with GnRH antagonist protocol using GnRH agonist for final oocyte maturation. The breast cancer group was additionally treated with letrozole (5 mg/d) from the first day of treatment until the day of oocyte retrieval. The cohort included 418 patients: 145 breast cancer patients, 168 with other oncological indications, and 105 patients who chose to undergo elective oocyte cryopreservation. There were no significant differences among the groups in the number of retrieved oocytes or proportion of mature oocytes. On multivariate linear regression models, co-treatment with letrozole was not a significant factor for the number of retrieved oocytes or for oocyte maturation rate after controlling for age, body mass index (BMI), and FSH dose. We conclude that the addition of letrozole to gonadotropins does not increase the number of oocytes retrieved or the oocyte maturation rate.

Morphokinetic characteristics of embryos derived from in-vitro-matured oocytes and their in-vivo-matured siblings after ovarian stimulation.

RESEARCH QUESTION: Does delayed maturation of aspirated metaphase I (MI) oocytes, completed in vitro, adversely affect early embryo development? DESIGN: Time-lapse microscopy was used to compare morphokinetic variables between embryos derived from oocytes with delayed maturation after ovarian stimulation and from in-vivo-matured metaphase II (MII) sibling oocytes from the same IVF and intracytoplasmic sperm injection cycle. RESULTS: A total of 1545 injected oocytes in 169 cycles from 149 patients were included. The in-vitro-matured oocytes had lower normal fertilization rates than the MII aspirated oocytes (50.2% versus 68.0%; P < 0.001). Early key developmental events were significantly delayed in the normally fertilized in-vitro-matured compared with in-vivo-matured oocytes (polar body extrusion: 5.4 ± 3 versus 3.9 ± 1.8 h; P < 0.001; pronuclear fading: 27.2 ± 4.7 versus 25.1 ± 4.2 h; P < 0.001, respectively) and synchrony of the second cell cycle was adversely affected. The proportions of embryos with optimal second cell cycle length and second cell cycle were similar but with fewer top-quality embryos, based on an algorithm, for the delayed in-vitro-matured oocytes compared with their in-vivo-matured sibling oocytes (14% versus 29.1%; P < 0.001). CONCLUSIONS: Embryos derived from oocytes that failed to mature in-vivo in standard treatment after ovarian stimulation may show a different morphokinetic profile from their sibling oocytes aspirated at the MII stage after completing maturation in-vivo.