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.

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.

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.

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.

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.

Endometrial thickness of less than 7.5 mm is associated with obstetric complications in fresh IVF cycles: a retrospective cohort study.

RESEARCH QUESTION: Does endometrial thickness affect the occurrence of obstetric complications in fresh IVF cycles? DESIGN: We conducted a retrospective cohort study that included all singleton deliveries resulting from fresh embryo transfers in a single centre between 2008 and 2014. Obstetric complications, i.e. preeclampsia, placental abruption, placenta previa, small for gestational age and preterm delivery, in singleton live births were compared among patients with an endometrial thickness of less than 7.5 mm and 7.5 mm or over on day of HCG triggering. We adjusted for confounders, including maternal age, body mass index, smoking, peak oestradiol, parity, chronic hypertension, pre-gestational diabetes, gestational diabetes, vanishing twin, inherited or acquired thrombophilia, and past pregnancy complications. RESULTS: A total of 5546 fresh embryo transfer cycles were carried out during the study period, of which 864 singleton deliveries met inclusion criteria. After adjusting for potential confounders, an endometrial thickness of less than 7.5 mm was found to be associated with increased risk for adverse obstetric outcome (adjusted OR 1.53; 95% CI 1.03 to 2.42; P = 0.04) even after excluding patients with prior pregnancy complications (adjusted OR 2.2; 95% CI 1.05 to 4.59; P = 0.035). CONCLUSIONS: Our results demonstrated that a thin endometrial lining was associated with obstetric complications that might be related to poor placentation. These findings should be validated in large prospective cohort studies.

A previous caesarean section is not a risk factor for tubal abnormalities in the infertile population.

In this retrospective cohort study of 1716 cases of women undergoing infertility treatment between the years 1999-2012, we aimed to identify whether parturients with a previous surgical history are at a higher risk for tubal abnormalities as determined by hysterosalpingography (HSG) in this infertile population. Amongst the study population, tubal obstruction was identified on HSG in 15.8% of patients with no past history of an abdominal surgery and 16.3% of patients with a previous caesarean section (CS) delivery. These rates were significantly lower than those for women with a previous gynaecological surgery (34.7%) or abdominal surgery (27%) (p < .001 for all comparisons). Our results suggest that past history of CS poses no additional risk for tubal abnormality within the infertile population, whereas a history of other abdominal or gynaecological surgical procedures doubles this risk. Impact Statement What is already known on this subject? While numerous risk factors for tubal factor infertility have been established, to date, the relation between previous abdominal surgeries and the risk for tubal factor infertility remains inconclusive. What the results of this study add? In this study, we aimed to evaluate the correlation between previous CS history and the risk for having tubal factor infertility. Our results demonstrated that previous caesarean section delivery does not increase the risk for tubal factor infertility in the infertile population, whereas history of other abdominal or gynaecological surgical procedures doubles this risk. What the implications are of these findings for clinical practice and/or further research? Further research is needed for further evaluation of this association and its clinical implications.

[LAPAROSCOPICALLY-ASSISTED ULTRASOUND-GUIDED PERCUTANEOUS TRANSABDOMINAL OOCYTE COLLECTION: FERTILITY PRESERVATION IN A 17-YEARS-OLD GIRL WITH VAGINAL EWING SARCOMA].

INTRODUCTION: Options for preserving fertility in children and adolescents with cancer depend on patient age, the available time frame, and the treatment regimen. Ovarian stimulation with mature oocyte preservation is often the optimal method in post-menarcheal adolescents. We describe a case of a 17-year-old girl with vaginal soft-tissue Ewing sarcoma in whom transvaginal oocyte collection for fertility preservation was ruled out by the large tumor. To overcome the limitations of the transabdominal approach, we applied a novel method of laparoscopically-assisted ultrasound-guided percutaneous transabdominal oocyte collection. In this manner, we were able to both perform oophorectomy and obtain superficial and deep ovarian follicles for cryopreservation.

Predictive value of serum HCG concentrations in pregnancies achieved after single fresh or vitrified-warmed blastocyst transfer.

Possible differences between serum HCG levels in pregnancies achieved after transfer of a single fresh or a vitrified-warmed blastocyst were evaluated. Out of 1130 single blastocyst transfers resulting in positive HCG results, 789 were single fresh blastocyst transfers and 341 single vitrified-warmed blastocyst transfers. The initial serum HCG levels of 869 clinical intrauterine pregnancies were evaluated, 638 after the transfer of a single fresh blastocysts and 231 after the transfer of a single vitrified-warmed blastocysts. The HCG levels from cycles resulting in a clinical intrauterine pregnancy were significantly higher after the transfer of a single vitrified-warmed blastocyst (383 ± 230 IU/l) versus a fresh transfer (334 ± 192 IU/l; P = 0.01). Threshold values for predicting a clinical pregnancy for a fresh blastocyst were 111 IU/l and for a vitrified-warmed blastocyst 137 IU/l. Our study shows that the overall beta-HCG levels are comparable after the transfer of a fresh or vitrified-warmed blastocyst, suggesting that vitrification most probably does not affect the ability of the embryos to produce beta-HCG. This study further shows that when clinicians counsel patients, they should take into account that higher HCG levels are needed after a vitrified-warmed blastocyst transfer to predict a clinical intrauterine pregnancy.

[FERTILITY PRESERVATION IN YOUNG CANCER PATIENTS - CAN WE OPTIMIZE THE PATH?]

INTRODUCTION: Advances in cancer therapy have improved the long-term survival of cancer patients. Concerns about fertility represent a major issue for young cancer patients. The emergent discipline of oncofertility, an intersection between oncology and fertility, is a new concept that describes an integrated network of clinical resources that focus on fertility preservation from both clinical and research perspectives. Patients and methods: In this article we describe our designated multidisciplinary program for fertility preservation in pediatric and young adult populations. The program is also designed to serve as a prospective platform for the evaluation of reproductive outcomes in this patient cohort. RESULTS: We have observed considerably higher referral rates following launching the program and earlier referral of chemonaïve patients that concedes maximal fertility preservation. Two hundred and thirty five patients were referred to the program over a period of 3 years. CONCLUSIONS: Our program demonstrates that multidisciplinary programs that encompass relevant specialists, skilled laboratory resources and a facilitated path that drives the process in the shortest time, maximizes the yield.

The effect of in vitro fertilization on coagulation parameters as measured by thromboelastogram.

OBJECTIVES: In vitro fertilization (IVF) induced elevated estrogen levels are associated with a hypercoagulable state. Thromboelastogram (TEG) is a point of care whole blood hemostasis analyzer which measures functionality of clotting parameters. Our study's objective was to examine the influence of the early and late follicular phase of an IVF simulation cycle on coagulation parameters as measured by TEG and to evaluate the influence of age on coagulation parameters. STUDY DESIGN: In a single center, prospective, observational trial, 46 women undergoing IVF therapy were studied. All women received a standardized IVF treatment protocol. Venous blood was drawn on the first day of the stimulation cycle and on the day of hCG injection and assessed by TEG. Parameters assessed by were R (represent clotting time), K and Angle (reflect clot strength and development), MA (maximum platelet-fibrin clot strength), CI (represents overall coagulability), and LY30 (represents lysis). RESULTS: Data from 46 women were analyzed. A statistically significant difference was found in all TEG parameters between early and late follicular phase, indicating a hypercoagulable state. R (p<0.0001), K (p=0.008), angle (p=0.008), MA (p=0.004), CI (p<0.001), LY30 (p=0.59). Age was a significant independent predictor for R at the early follicular phase (p=0.042). Both age and estrogen levels were found to be independent predictors for CI at late follicular phase. Age (p=0.011), estrogen (p=0.019). CONCLUSIONS: There was a significant difference in all coagulation parameters between early and late follicular phase, indicating a hypercoagulable state.

Early maternal serum ß-human chorionic gonadotropin (ß-hCG) levels and sex-related growth difference of IVF embryos.

PURPOSE: Maternal serum ß-human chorionic gonadotropin (ß-hCG) represents the trophoblastic cell mass and is an indirect measurement of embryo development at early implantation stage. Studies in animals and human embryos detected sex-related growth differences (SRGD) in favour of male embryos during the pre-implantation period. The purpose of our study was to correlate SRGD and maternal serum ß-hCG at 16 days after embryo transfer. METHODS: We retrospectively analysed all (fresh and frozen) non-donor, single embryo transfers (SET), elective and not elective, that were performed between December 2008 and December 2013. We included ß-hCG values from day 16 after oocyte collection of pregnancies resulting in live birth. Neonatal gender was retrieved from patient files. Male and female embryos were further grouped to cleavage and blastocyst stage transfers. Regression analysis for confounding variables included maternal age, maternal body mass index (BMI), use of micromanipulation (ICSI), embryo quality (grade), assisted hatching, day of transfer and fresh or frozen embryo transfer. RESULTS: Seven hundred eighty-six non-donor SETs resulted in live birth. After including only day 16 serum ß-hCG results, 525 SETs were analysed. Neonatal gender was available for 522 cases. Mean maternal serum ß-hCG levels were similar, 347 ± 191 IU/L in the male newborn group and 371 ± 200 IU/L in the female group. The difference between ß-hCG levels remained insignificant after adjusting for confounding variables. CONCLUSIONS: Early maternal ß-hCG levels after embryo transfers did not represent SRGD in our study.

Obstetric and perinatal outcome from single cleavage transfer and single blastocyst transfer: a matched case-control study.

AIM: To evaluate a possible relationship between extended embryo culture and outcome of pregnancies resulting from single embryo transfers (SETs). DESIGN: A retrospective matched case-control study Setting: University fertility center Patients: About 106 live births from single cleavage embryo transfers were matched 1:2 with 212 live births from single blastocyst transfers. INTERVENTIONS: A cohort of 3522 fresh SETs using non-donor oocytes in women ≤40 years old from August 2010 to December 2013. Live births were matched by maternal age, body mass index, smoking and parity. Adjustments were made for gender of the baby and embryo quality. Obstetric and perinatal outcomes including birth weight, low birth weight, small for gestational age, preterm delivery, preeclampsia, placental abruption and neonatal complications were compared. RESULTS: Matched live birth outcomes showed no increased risk of obstetric or perinatal complications in pregnancies resulting from single blastocyst transfers compared to single cleavage transfers. CONCLUSIONS: Extended culture was not associated with increased adverse obstetric and perinatal outcome in pregnancies resulting from fresh SETs in this study.

Progesterone-to-follicle index is better correlated with in vitro fertilization cycle outcome than blood progesterone level.

OBJECTIVE: To investigate the impact of late follicular phase progesterone (P) elevation in relation to ovarian response on cycle outcome. DESIGN: Cohort study. The progesterone-to-follicle index (PFI) was calculated by dividing the blood P by the number of follicles ≥14 mm. The clinical pregnancy rate was calculated against the range of PFI values and blood P levels. SETTING: In vitro fertilization unit. PATIENT(S): A heterogenous population undergoing IVF with pituitary suppression and gonadotropin stimulation resulting in 3-15 follicles ≥14 mm and blood P≤10 nmol/L on hCG day and resulting in fresh embryo transfer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Association of blood P and PFI with clinical pregnancy rate. RESULT(S): Data were retrieved for 8,649 IVF cycles in normal responders. The (reverse) odd ratios for pregnancy were 1.112 (95% confidence interval [CI], 1.077-1.165) for blood P and 4.104 (95% CI, 3.188-5.284) for the PFI. Elevated P levels were associated with a lower pregnancy rate only when they reached the >93rd percentile. The PFI was inversely and linearly related to the pregnancy rate for the whole range of values. CONCLUSION(S): A late increase in P level is detrimental if it is a consequence of increased P production per follicle (high PFI) but not if it is a consequence of additional follicular recruitment. The PFI enables clinicians to differentiate these conditions.

The association between embryo quality and perinatal outcome of singletons born after single embryo transfers: a pilot study.

STUDY QUESTION: Does the quality of a single transferred embryo have an effect on the pregnancy outcome? SUMMARY ANSWER: After adjusting for confounding maternal variables, poor embryo quality was not associated with adverse obstetric or perinatal outcome in this small pilot study. WHAT IS ALREADY KNOWN: Embryo quality is a major predictor of the success of in vitro fertilization treatment and studies have demonstrated a strong association between embryo morphology, implantation and clinical pregnancy rates. However, the association with obstetric and perinatal outcomes has not been evaluated. STUDY DESIGN, SIZE AND DURATION: This single center, retrospective cohort study included 1541 fresh single embryo transfers (SETs) using non-donor oocytes in women ≤40 years between December 2008 and 2012. We compared the cycle outcome and singleton live births resulting from the transfer of a single fresh good quality (Grade 2) embryo with those resulting from the transfer of a single poor quality (fair, Grade 3 or poor, Grade 4) embryo in the cleavage or blastocyst stages. PARTICIPANTS/MATERIALS, SETTING, METHODS: The cycle outcome parameters were biochemical pregnancy and clinical intrauterine pregnancy. The pregnancy outcomes were live birth, miscarriages and stillbirths after 20 weeks of gestation. Among the live births, perinatal outcome parameters included birthweight, small for gestational age, preterm delivery, pre-eclampsia, placental abruption and neonatal complications. Covariates were maternal age, body mass index, smoking status, parity and gender of the baby. MAIN RESULTS AND ROLE OF CHANCE: There were 1193 good quality SETs and 348 poor quality embryo transfers. SETs performed during the study period resulted in 563 pregnancies and 440 singleton births. There was a higher clinical pregnancy rate (41.5%) and live birth rate (32.3%) in the good quality embryo transfer group compared with that in the poor quality transfer group (19.2 and 15.5%, respectively; P < 0.0001). There was no significant difference in the miscarriage rate between the transfers of a single good or poor quality embryo. Multivariable logistic regression analyses for pregnancy complications revealed no increased risk of maternal or neonatal complications with the transfer of a poor quality embryo. There was no difference in the obstetric or perinatal outcome of the live births resulting from a good or poor quality embryo after stratification by day of transfer. LIMITATIONS, REASONS FOR CAUTION: The main limitations of this study are the retrospective nature of the study, the relative subjectivity of embryo scoring and the small number of live births after transfer of poor quality embryos. WIDER IMPLICATIONS OF THE FINDINGS: Our findings may be used to reassure women that transfer of a single poor quality embryo, whether a cleavage or a blastocyst, does not appear to be associated with increased risks of adverse obstetric and perinatal outcomes. STUDY FUNDING/COMPETING INTEREST (S): Only internal funding was used. There is no conflict of interest in relation to the study.

Extended embryo culture is not associated with increased adverse obstetric or perinatal outcome.

OBJECTIVE: We sought to compare obstetric and perinatal outcomes of singletons born after extended embryo culture and a single blastocyst stage embryo vs a single cleavage stage embryo transfer. STUDY DESIGN: This was a retrospective cohort study of 1543 fresh single embryo transfers using nondonor oocytes in women ≤40 years old from December 2008 through December 2012 at the reproductive unit of McGill University Health Center. The main outcome measures were perinatal outcomes including birthweight, low birthweight, small for gestational age, preterm delivery, preeclampsia, placental abruption, and neonatal complications. Covariates were maternal age, body mass index, smoking, cause of infertility, parity, and sex of the baby. RESULTS: Transfers of 693 fresh single cleavage embryos and 850 fresh single blastocysts resulting in 564 pregnancies and 381 singleton deliveries were analyzed. Blastocyst transfer resulted in a higher clinical pregnancy rate (50.1% and 19.9%) and live birth rate (33.5% and 13.8%) compared to cleavage embryo transfer, respectively (P < .001). Multivariate analyses for pregnancy revealed no increased risk of maternal or neonatal complications in pregnancies resulting from extended embryo culture. CONCLUSION: Live births resulting from extended embryo culture and a single blastocyst transfer are not associated with increased adverse obstetric and perinatal outcome compared to live births from a single cleavage embryo transfer in women ≤40 years old.