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

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

'Luckily, I don't believe in statistics': survey of women's understanding of chance of success with futile fertility treatments.

RESEARCH QUESTION: Why are women who face poor prognoses for success in assisted reproductive technology (ART) treatment choosing to pursue procedures using their own eggs, despite receiving information that their chances of success are very low. DESIGN: Cross-sectional study based on an anonymous questionnaire distributed to women aged between 43 and 45 years, undergoing ART using their own oocytes, at six public outpatient fertility clinics and three public in-hospital IVF units in Israel between 2015 and 2016. The main outcome measure was personal estimation of chance to achieve a live birth after the current ART treatment cycle and the cumulative estimated rate after all the treatment cycles the patient intended to undergo. RESULTS: Response rate was 70.0%, with 91 participants of mean age 43.8 ± 0.7 years. Participants estimated their delivery rates after the next ART treatment cycle at 49.0 ± 31.8% (response rate 93.4%) and their cumulative delivery rates after all the ART treatments they would undergo at 57.7 ± 36.3% (response rate 90.1%). This is significantly higher than the predicted success rates of 5% and 15%, respectively (both P < 0.001), which are based on national register data. Nearly one-half of patients rated themselves as having a better than average chance of conception (47.3%). CONCLUSION: Women do not pursue futile treatments because they lack information. Despite being informed of the low success rates of conception using ART treatments, many patients of advanced maternal age have unrealistically high expectations from ART, essentially ignoring their estimated prognosis when deciding on treatment continuation. Future work should examine the psychological reasons behind continuing futile fertility treatments.

Cancer in IVF patients treated at age 40 years and older: long term follow-up.

RESEARCH QUESTION: Current knowledge of cancer risk among women who undergo IVF is based mainly on studies of women treated in their thirties, frequently with short follow-up periods. Therefore, information about cancer risk among infertile menopausal women is limited. We aimed to evaluate the risk of cancer among IVF patients treated at age 40 years and older, followed up for an extended period. DESIGN: Historical cohort study of all IVF patients treated at the age of 40 years or older at two university-affiliated IVF units in Jerusalem, Israel, between 1994 and 2002. Data were cross-linked with the Israel National Cancer Registry to 2016. Standardized incidence ratios (SIR) and 95% confidence intervals were computed by comparing the observed number of cancer cases with the expected cancer rate in the general Israeli population adjusted for age and year of birth. In addition, Kaplan-Meier analysis was conducted to account for the length of follow-up. RESULTS: A total of 501 patients were included in the analysis, with mean follow-up of 16.7 ± 3.7 years (range 2-22 years). Mean age at first IVF cycle was 42.3 years (±2.1). Mean number of IVF cycles was 3.2 ± 2.6 (range 1-15). Thirty-six women (7.2%) developed invasive cancer, compared with 47.2 expected cases; SIR 0.76 (95% CI 0.53 to 1.06); 22 women were diagnosed with invasive breast cancer, compared with 19.84 expected; SIR 1.11 (95% CI 0.69 to 1.68). CONCLUSIONS: Older women undergoing IVF treatment were not significantly associated with an excess risk of cancer at long-term follow up. Further studies, however, are needed to confirm these findings.

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

PURPOSE: To evaluate fertility preservation outcomes in breast cancer women with different hormonal receptor profiles before oncological treatment. METHODS: 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 > 14 mm on the final oocyte maturation trigger day. RESULTS: 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 > 14 mm 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). CONCLUSION: Among the different hormonal receptor profiles in breast cancer, the TNBC subtype has a negative effect on fertility preservation outcomes.

Searching the Internet for Infertility Information: A Survey of Patient Needs and Preferences.

BACKGROUND: Given the complexity of infertility diagnoses and treatments and the convenience of the internet for finding health-related information, people undergoing infertility treatments often use Web-based resources to obtain infertility information and support. However, little is known about the types of information and support resources infertility patients search for on the internet and whether these resources meet their needs. OBJECTIVE: The aims of this study were to (1) examine what individual factors, namely, demographic characteristics and distress, are associated with searching the internet for different types of infertility-related information and support resources and (2) determine whether Web-based resources meet the needs of patients. METHODS: Men and women seeking infertility care responded to a survey assessing use of Web-based resources for accessing infertility-related information and support. The survey further assessed satisfaction with Web-based resources as well as perceived stress and depressive symptomatology. RESULTS: A total of 567 participants, including 254 men and 313 women, completed the survey. Most participants (490/558, 87.8%) had searched the internet for infertility information and support. Searchers were more likely to be women (P<.001), highly educated (P=.04), long-term patients (P=.03), and more distressed (P=.04). Causes of infertility, treatment options, and scientific literature about infertility were the three most frequently searched topics, whereas ways to discuss treatment with family and friends as well as surrogacy and ways to find peer support were the three least searched topics. Of those who searched the internet, 70.9% (346/488) indicated that their needs were met by Web-based information, whereas 29.1% (142/488) said that their needs were not met. Having unmet needs was related to greater levels of perceived stress (P=.005) and depressive symptomatology (P=.03). CONCLUSIONS: This study provides evidence for the important role of the internet in accessing infertility information and support and for the ability of Web-based resources to meet patients' needs. However, although distressed patients reported particularly high rates of searching, their needs were not always met, suggesting that they may benefit from alternative sources of information and support or guidance from health care providers when searching the internet.

The effect of repeated biopsy on pre-implantation genetic testing for monogenic diseases (PGT-M) treatment outcome.

PURPOSE: To study the outcome of repeated biopsy for pre-implantation genetic testing in case of failed genetic diagnosis in the first biopsy. METHODS: The study group included 81 cycles where embryos underwent re-biopsy because there were no transferable embryos after the first biopsy: in 55 cycles, the first procedure was polar body biopsy (PBs) and the second cleavage-stage (BB); in 26 cycles, the first was BB and the second trophectoderm (BLAST) biopsy. The control group included 77 cycles where embryos underwent successful genetic diagnosis following the first biopsy, matched by maternal age, egg number, genetic inheritance type, and embryonic stage at the first biopsy. We measured genetic diagnosis rate, clinical pregnancy rates (PRs), live-birth rates (LBRs), gestational age, and birth weight. RESULTS: For repeated biopsy, genetic diagnosis was received in 67/81 cycles (82.7%); at a higher rate in PB + BB than in BB + BLAST (49/55, 89.1% and 18/26, 69.2% respectively, p = 0.055). Transferable embryos were found in 47 and 68 cycles in the study and the control groups. PRs/ET were 20/47 (42.6%) and 36/68 (52.9%) (p = 0.27), 16/36 (44.4%) following PB + BB, and 4/11 (36.4%) following BB + BLAST (p = 0.74). LBRs/ET were 13/47 (27.7%) in study group, and 28/68 (41.2%) in the controls (p = 0.14), 10/36 (27.8%) following PB + BB group, and 3/11 (27.3%) following BB + BLAST (p > 0.99). Gestational age and birth weight were similar in all groups. CONCLUSIONS: Re-biopsy of embryos when no genetic diagnosis could be reached following the first biopsy, achieved high rates of genetic diagnosis, pregnancies, and live births.

The influence of body mass index on pregnancy outcome following single-embryo transfer.

PURPOSE: The association between obesity and reproductive outcome is controversial. The aim of this study is to evaluate the effects of obesity on clinical pregnancy rates following transfer of a single fresh embryo. METHODS: A retrospective cohort study was conducted at a single tertiary medical center, including all first, fresh, single-embryo transfers using non-donor oocytes, during 2008-2013. We compared clinical pregnancy rate and pregnancy outcomes of singleton live births resulting from the transfer of a single fresh embryo in normal weight, overweight, and obese women, defined as body mass index (BMI) < 25 kg/m2, ≥ 25 BMI <30 kg/m2, and BMI ≥ 30 kg/m2, respectively. RESULTS: Overall, 1345 cases met the inclusion criteria with 864 single-embryo transfers (SETs) in normal weight women, 292 in overweight women, and 189 SETs in obese women, resulting in 538 clinical pregnancies and 354 singleton births. The clinical pregnancy rate per transfer was similar among the three groups (41.3, 37.6, 37.5%, respectively, p = 0.416). Similarly, there were no significant differences in live births or ongoing pregnancies. On multivariate logistic regression analysis, BMI did not impact the likelihood for clinical pregnancy (OR 0.98, 95% CI 0.96-1.008, p = 0.216). CONCLUSIONS: Our study demonstrated that obesity has no detrimental effect on the clinical pregnancy rate resulting from the transfer of a single fresh embryo.

Vitrified-warmed single-embryo transfers may be associated with increased maternal complications compared with fresh single-embryo transfers.

Cryopreservation of embryos allows single-embryo transfer and storage of supernumerary embryos, maximizing cumulative pregnancy rates. The purpose of this retrospective cohort study was to compare pregnancy outcome in singletons born after fresh or vitrified-warmed single blastocyst transfer (SBT). Singleton live births resulting from SBT of fresh or vitrified-warmed embryos were compared. Primary outcomes were perinatal outcomes including small for gestational age (SGA), low birthweight, preterm deliveries (PTD), large for gestational age (LGA) and congenital malformations. Maternal complications included pre-eclampsia, placenta previa, placental abruption, gestational diabetes mellitus (GDM) and chorioamnionitis. Adjustment for confounding factors was performed. Of 1886 fresh SBTs and 1200 vitrified-warmed SBTs during the study period, vitrified-warmed SBTs compared with fresh SBTs resulted in significantly lower clinical pregnancy rate (P < 0.0001). Live birth and miscarriage rates calculated only for pregnancy with known outcome revealed lower live birth rates and higher miscarriage rates for the vitrified-warmed group. Perinatal complications were calculated for clinical pregnancies with known outcomes (12.9% catchment failure was excluded from analysis). The vitrified-warmed group showed a trend toward higher rates of pre-eclampsia, GDM, Caesarean delivery and LGA neonates. Rates of PTD and SGA were comparable. In conclusion, vitrified-warmed SBT might be associated with increased feto-maternal complications.

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.

Cryopreserved embryo transfer: adjacent or non-adjacent to failed fresh long GnRH-agonist protocol IVF cycle.

The optimal time to perform cryopreserved embryo transfer (CET) after a failed oocyte retrieval-embryo transfer (OR-ET) cycle is unknown. Similar clinical pregnancy rates were recently reported in immediate and delayed CET, performed after failed fresh OR-ET, in cycles with the gonadotrophin-releasing hormone (GnRH) antagonist protocol. This study compared outcomes of CET performed adjacently (<50 days, n = 67) and non-adjacently (≥50 to 120 days, n = 62) to the last OR-day of cycles with the GnRH agonist down-regulation protocol. Additional inclusion criteria were patients' age 20-38 years, the transfer of only 1-2 cryopreserved embryos, one treatment cycle per patient and artificial preparation for CET. Significantly higher implantation, clinical pregnancy and live birth rates were found in the non-adjacent group than in the adjacent group: 30.5% versus 11.3% (P = 0.001), 41.9% versus 17.9% (P = 0.003) and 32.3% versus 13.4% (P = 0.01), respectively. These results support the postponement of CET after a failed OR-ET for at least one menstrual cycle, when a preceding long GnRH-agonist protocol is used.

A prospective study using Hatha Yoga for stress reduction among women waiting for IVF treatment.

Yoga has been found to be effective in treating anxiety and depression, reducing stress and improving the overall quality of life in the general population. Minimal research is available on the effect of stress-management programmes with IVF patients. Owing to the diversity of conditions treated, the poor quality of most studies, and the different assessment tools used to evaluate the psychological state, it is difficult to draw definite conclusions. Previous studies have used different mind-body interventions and general measures of stress without evaluation of specific stresses known to result from infertility and its treatment using standardized measures. In this single-centre study, 49 infertile women were recruited to participate in a 6-week Yoga class during 2013 while awaiting their IVF treatment. Study participants were asked to complete standardized questionnaires assessing fertility-related quality of life (FertiQoL), marital harmony (Dyadic Adjustment Scale [DAS]), state and trait anxiety (State-Trait Anxiety Inventory [STAI]) and depression (Beck Depression Inventory [BDI]) before commencing and after completing the Yoga workshops. Anxiety, depression and fertility-specific quality of life showed improvement over time in association with participation in a 6-week Yoga programme in women awaiting their treatment with IVF.

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.

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.

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.

In-vitro maturation versus IVF with GnRH antagonist for women with polycystic ovary syndrome: treatment outcome and rates of ovarian hyperstimulation syndrome.

In-vitro maturation (IVM) treatment has gained popularity for decreasing the incidence of ovarian hyperstimulation syndrome (OHSS) by eliminating or minimizing the use of gonadotrophins in women with polycystic ovary syndrome (PCOS). Studies have shown that IVF with GnRH-antagonist protocol is associated with a lower incidence of OHSS. Data comparing the relative success of these two treatments is, however, lacking. Treatment outcome and rates of OHSS were compared in patients with PCOS who underwent assisted conception with either IVM or IVF with GnRH-antagonist protocol between 2006 and 2011. The number of oocytes retrieved was higher in the IVM group, whereas the number of mature oocytes, fertilization rate and number of embryos cleaved were comparable. The implantation rate was higher in the IVF group. The clinical pregnancy rates per embryo transfer were not statistically different (IVF: 45.8% versus IVM: 32.4%). The live-birth rate was higher in the IVF group (IVF: 40.7% versus IVM: 23.5%; P = 0.04). Five women developed moderate or severe OHSS in the IVF group, whereas none did in the IVM group. Both IVM and IVF with GnRH-antagonist protocol seem to be effective treatment regimens in women with PCOS, although IVM is associated with a lower risk of OHSS.

Chromosomal complement and clinical relevance of multinucleated embryos in PGD and PGS cycles.

The objective of this retrospective study was to investigate the incidence and clinical implications of multinucleation in blastomeres biopsied from cleavage-stage embryos obtained from patients undergoing preimplantation genetic screening (PGS) for aneuploidies or preimplantation genetic diagnosis (PGD) for translocations or single-gene defects (SGD). A total of 3515 embryos were obtained from 306 couples in 380 PGD or PGS cycles. Incidence of multinucleation, chromosomal complement in multinucleated (MN) and sibling embryos and the characteristics of MN embryos resulting in healthy births were investigated. Of all cycles, 41.3% involved at least one MN embryo. There were more uniformly diploid than uniformly haploid nuclei (22.0% versus 7.9%, P<0.01). The most common form of abnormality was chaotic chromosomal complement (39.9%, 147/368). Transfer of embryos that had MN blastomeres free of the genetic abnormalities tested resulted in three healthy deliveries. It is concluded that, although the majority of MN blastomeres are chromosomally abnormal, healthy births are possible after transfer of embryos containing these blastomeres subjected to genetic analysis. As far as is known, this is the first report of healthy births after transfer of embryos with MN blastomeres tested for translocations or SGD in PGD cycles. Preimplantation genetic diagnosis (PGD) is an established method for selecting genetically healthy embryos for transfer. A blastomere sampled from the developing embryo is subjected to genetic analysis. Some of these blastomeres may contain multiple nuclei, complicating the genetic diagnosis. We investigated clinical implications of multinucleation in PGD cycles. Our results indicate that majority of the multinucleated blastomeres, and consequently embryos, are genetically abnormal. However, healthy births are possible after transfer of multinucleated embryos that are free of the genetic abnormalities screened.

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.

Lateralization of ovarian follicles.

BACKGROUND/AIM: To evaluate a possible lateralization of antral follicle count (AFC) based on the finding that endometriosis, if present, is more commonly found in the left hemipelvis. METHODS: We evaluated the records of 6,617 baseline ultrasounds conducted at our Reproductive Center between 2007 and 2011 in a university teaching hospital setting. We included all ultrasounds with an AFC of 1 or greater and excluded those with incomplete documentation or with ovarian cyst, including endometriotic cysts (n = 909). The main outcome measure was the comparison of the number of antral follicles between the right and left ovary. RESULTS: The number of antral follicles in the right ovary (median 18, range 15-22) was significantly higher than in the left ovary (median 16, range 13-20) among women with polycystic ovaries (PCO, AFC ≥24). Similarly, the number of antral follicles in the right ovary (median 8, range 6-10) was significantly higher than in the left ovary (median 7, range 5-9) in women with no PCO but normal ovarian reserve (AFC 10-23). CONCLUSIONS: In women with PCO and non-PCO with normal ovarian reserve, the right ovary contains a higher number of antral follicles than the left ovary.

Spindle examination in unfertilized eggs using the polarization microscope can assist rescue ICSI.

Rescue ICSI can induce a high rate of 3 pronuclei (PN) formation from double insemination in eggs already fertilized by IVF but lacking signs of normal pronuclear formation. This study was performed to determine whether the number of 3PN embryos could be reduced by using the polarization microscope for rescue intracytoplasmic sperm injection (ICSI). As a study group, after conventional insemination, 81 unfertilized mature oocytes from 11 couples were checked for the number of spindles using the polarization microscope. One spindle (82.7%) or two spindles (17.3%) were observed in this group. Rescue ICSI was only performed on the unfertilized oocytes showing one spindle. In the control group, 87 mature oocytes which lacked visualization of any fertilization signs were selected for rescue ICSI and none of them underwent observation of the spindle. After rescue ICSI, the normal fertilization rate in the study group was significantly higher than in the control (68.7% versus 43.7%; P=0.0032). The rate of 3PN or 4PN embryos was significantly decreased in the study group with one spindle compared with the group without observation of the spindle (4.5% versus 26.4%; P=0.0004).

Age-related normogram for antral follicle count in women with polycystic ovary syndrome.

Antral follicle count (AFC) has been shown to be a reliable marker for ovarian reserve. The aims of this study were to create an age-related normogram for AFC in infertile women with polycystic ovary syndrome (PCOS) and to compare age-related decline in AFC between infertile women with and without PCOS. A retrospective cohort study was conducted. Of a total of 4956 women, 619 women fit criteria for PCOS. In those with PCOS, there were large variations in the AFC between the 10th and 90th percentiles in all age groups. The rate of decline in AFC among women with PCOS was linear, while in those with non-PCOS, it was exponential until 30 years of age, and then became similar to that of PCOS. The rate of follicle loss per year was significantly slower in PCOS women compared with that in non-PCOS women. In both groups, the fastest period of follicle loss was between the ages of 18 and 30. The average follicle loss was 0.8 follicles/year in PCOS women and 1.7 follicles/year in those without PCOS (P<0.001). This study concludes that age-related decline in AFC among women with PCOS is slower than in those without PCOS. Antral follicle count (AFC) has been shown to be a reliable marker for ovarian reserve. The aims of this study were to create an age-related normogram for AFC in women with polycystic ovary syndrome (PCOS), and to compare age-related decline in AFC between women with and without PCOS. A retrospective cohort study was conducted. All patients underwent a baseline transvaginal ultrasound that was performed on day 2-4 of the menstrual cycle. The total number of antral follicles of 2-9mm in diameter was recorded. Of total 4956 women, 619 women fit criteria for PCOS. In those with PCOS, there were large variations in the AFC between the 10th 90th percentiles in all age groups. The rate of decline in AFC among women with PCOS was linear; while in those with non-PCOS, it was exponential until 30 years of age, and then became similar to that of PCOS. The rate of follicle loss per year was significantly slower in PCOS women compared with that in non-PCOS women. In both groups, the fastest period of follicle loss was between the ages 18-30 years. The average follicle loss was 0.8 follicles/year in PCOS women and 1.7 follicles/year in those without PCOS (P<0.001). We have concluded that age-related decline in AFC among women with PCOS is slower than in those without PCOS. Further studies are needed to determine if the AFC normogram in women with PCOS could be clinically relevant to select the optimal gonadotrophin dose for ovulation induction.