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.

Consecutive ovarian stimulation is beneficial in patients with a poor response to high-dose follicle-stimulating hormone.

OBJECTIVE: To investigate if an immediate additional IVF-ET cycle bear an advantage to patients with poor ovarian response in comparison to a cycle performed at some delay. METHODS: A cohort study including 632 patients who underwent a fresh IVF-ET cycle with high-dose (≥300 IU/d) FSH stimulation that yielded ≤4 oocytes and did not achieve a clinical pregnancy. All underwent a second stimulation and oocyte pick-up (OPU), either consecutively or separately within 180 days (nonconsecutive OPU). The oocyte yield, number of embryos available for transfer, pregnancy live birth rates of the second OPU were compared between patients who had consecutive and nonconsecutive cycles. RESULTS: Consecutive OPU was associated with more mature follicles in the second cycle compared to nonconsecutive OPU (p = .03) in addition to higher peak estradiol level (p < .0001), and more aspirated oocytes (p = .03) and available embryos (p = .023). There was no between-group difference in ongoing pregnancy and live birth rates. In a multivariate analysis of variance controlling for potential confounders, the difference in the number of aspirated oocytes and available embryos was associated significantly only with consecutive performance of the second cycle. CONCLUSION: Immediate sequential stimulation (without an intervening menstrual cycle) in poor responders is advantageous over delayed stimulation in terms of number of aspirated oocytes and available embryos. The administration of high-dose FSH in the first cycle may benefit follicular recruitment also in the subsequent cycle. Although the effect is modest, given that each additional oocyte aspirated contributes to the outcome, it might be of significance especially in younger patients.

Frozen-thawed embryo transfer is an independent risk factor for third stage of labor complications.

PURPOSE: Third stage of labor complications are more prevalent following singleton vaginal deliveries of gestations conceived through in vitro fertilization (IVF) and fresh embryo transfer. This study aimed to evaluate these complications in pregnancies conceived through frozen-thawed embryo transfer (FET), in which endometrial preparation differs from fresh cycles. METHODS: A cohort study of all singleton pregnancies conceived through IVF-FET who delivered vaginally at a tertiary medical center during 2007-2017. The study group consisted of 88 IVF-FET gestations (cases) that were matched to 176 spontaneous pregnancies based on age, gravidity, parity and gestational week at delivery (controls). The association between mode of conception and third stage of labor complication rate was examined. RESULTS: Baseline characteristics were similar between groups, except for a lower prevalence of induction of labor in the control group (23.3% vs. 36.3%, p = 0.03). The rate of post-partum hemorrhage (PPH), manual lysis and revision of the uterine cavity were all higher in pregnancies conceived through IVF-FET versus spontaneously (13.6% vs. 5.7%, p = 0.018; 17% vs. 2.3%, p < 0.001; and 21.6% vs. 6.8%, p < 0.001, respectively). Multivariate analysis adjusting for age, previous cesarean section, induction of labor, neonatal weight and use of analgesia demonstrated that deliveries following IVF-FET were independently associated with an increased risk for third stage of labor complications (estimated OR = 3.45, p = 0.0002). CONCLUSION: IVF-FET is an independent risk factor for PPH, need for manual lysis and revision of the uterine cavity. Precautionary measures should be undertaken in the third stage in deliveries following IVF-FET, even if no other risk factors are present.

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.

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.

Oocyte retrieval outcomes among adolescent transgender males.

PURPOSE: To compare fertility preservation (FP) outcomes among adolescent transgender males with those of cisgender females. METHODS: This retrospective cohort study included nine adolescent transgender males and 39 adolescent cisgender females who underwent FP between January 2017-April 2019 and September 2013-April 2019, respectively. The transgender males were referred before initiating testosterone, and the cisgender females were referred due to cancer diagnosis before starting anticancer treatment. Statistical analyses compared assisted reproductive technology (ART) data and FP outcomes between two groups. RESULTS: Basal FSH levels (5.4 ± 1.7 mIU/mL) and AFC (19.8 ± 5.6) of all transgender males were normal compared with standard references. The mean age of transgender males and cisgender females was similar (16.4 ± 1.1 vs 15.5 ± 1.3 years, respectively, P = 0.064). The amount of FSH used for stimulation was significantly lower among the former compared with the latter (2416 ± 1041 IU vs 4372 ± 1877 IU, P < 0.001), but the duration of stimulation was similar (12.6 ± 4.0 and 10.1 ± 2.8 days, P = 0.086). Peak estradiol level was significantly higher among transgender males compared with cisgender females (3073 ± 2637 pg/mL vs 1269 ± 975 pg/mL, respectively, P = 0.018), but there were no significant differences in number of retrieved oocytes between the two groups (30.6 ± 12.8 vs 22 ± 13.2, P = 0.091), number of MII oocytes (25.6 ± 12.9 vs 18.8 ± 11.2, P = 0.134), or maturity rates (81.5 ± 10.0% vs 85.4 ± 14.6%, P = 0.261). CONCLUSIONS: Adolescent transgender males have an excellent response to ovulation stimulation before initiating testosterone treatment. Oocyte cryopreservation is, therefore, a feasible and effective way for them to preserve their fertility for future biological parenting.

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.

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.

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.

[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.

[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.

Pregnancy outcome after ICSI with thawed testicular sperm from men with non-obstructive azoospermia compared to ICSI with ejaculated sperm from men with severe oligoasthenoteratozoospermia and IVF with normal ejaculated sperm.

The aim of the study was to evaluate the clinical pregnancy outcomes, fetal complications and malformation rate of intracytoplasmic injection of thawed cryopreseverd sperm extracted by testicular aspiration from men with non-obstructive azoospermia (NOA) compared with intracytoplasmic injection of fresh ejaculated sperm from men with severe oligoteratoasthenozoospermia (OTA) and standard in vitro fertilization using ejaculated sperm from normospermic men. The mean oocyte fertilization rate was significantly lowest for ICSI with testicular aspirated sperm (NOA group). However, there was no significant difference among the three groups in pregnancy outcomes, namely rates of spontaneous abortion, biochemical pregnancy, extrauterine pregnancy, singleton multifetal pregnancy, preterm delivery before 36 weeks' gestation, maternal complications, transfer to the neonatal intensive care unit, intrauterine growth restriction or fetal malformations. These results suggest that despite some earlier findings that intracytoplasmic injection of aspirated sperm from men with NOA is associated with lower fertilization rates and embryo quality, the pregnancy and immediate neonatal outcomes may be unaffected.

Poor Response to Gonadotropin Stimulation and Perinatal Outcomes in Fresh In Vitro Fertilization Embryo Transfer Cycles-A Retrospective Cohort Study.

Objective: The objective was to examine the association between poor ovarian response to gonadotropin stimulation for in vitro fertilization (IVF) and adverse perinatal outcomes in singleton gestations in young patients. Methods: This was a retrospective cohort study including women aged 17-39 who underwent fresh embryo transfer and delivered a singleton neonate at a single center (pre-implantation genetic testing excluded) (2007-2022). Patients were classified as one of the following categories: poor responders-daily follicle-stimulating hormone (FSH) ≥ 150 IU yielding ≤ 3 retrieved oocytes; normal responders-4-15 oocytes; and high responders with ≥16 oocytes. The primary outcome was a composite of pre-eclampsia (mild or severe), small-for-gestational-age, gestational diabetes mellitus, and preterm birth (<37 weeks). We compared maternal and neonatal outcomes between the three groups. Multivariable logistic regression was used to control for confounders. Results: Overall, 507 women met the inclusion criteria. Of them, there were 44 (8.68%) poor responders, 342 (67.46%) normal responders, and 121 (23.87%) high responders. Poor responders, compared to normal and high responders, were characterized by a higher maternal age (34.64 ± 4.01 vs. 31.4 ± 5.04 vs. 30.01 ± 4.93, p < 0.001, respectively) and total FSH dosage (3028.41 ± 1792.05 IU vs. 2375.11 ± 1394.05 IU vs. 1869.31 ± 1089.63 IU, p < 0.001). The perinatal outcomes examined, including cesarean delivery (CD) rate and the composite outcome, were comparable between groups. Using multivariable logistic regression and adjusting for ovarian response group, maternal age, nulliparity, and estradiol level and endometrial thickness before ovulation triggering, poor response was not associated with CD rate or the composite outcome, with maternal age associated with CD (p = 0.005), and nulliparity with the composite outcome (p = 0.007). Similar results were obtained when comparing poor responders to each other group separately or to all other responders. Conclusions: Poor ovarian response is not associated with increased adverse maternal or neonatal outcomes.

An artificial intelligence algorithm for automated blastocyst morphometric parameters demonstrates a positive association with implantation potential.

Blastocyst selection is primarily based on morphological scoring systems and morphokinetic data. These methods involve subjective grading and time-consuming techniques. Artificial intelligence allows for objective and quick blastocyst selection. In this study, 608 blastocysts were selected for transfer using morphokinetics and Gardner criteria. Retrospectively, morphometric parameters of blastocyst size, inner cell mass (ICM) size, ICM-to-blastocyst size ratio, and ICM shape were automatically measured by a semantic segmentation neural network model. The model was trained on 1506 videos with 102 videos for validation with no overlap between the ICM and trophectoderm models. Univariable logistic analysis found blastocyst size and ICM-to-blastocyst size ratio to be significantly associated with implantation potential. Multivariable regression analysis, adjusted for woman age, found blastocyst size to be significantly associated with implantation potential. The odds of implantation increased by 1.74 for embryos with a blastocyst size greater than the mean (147 ± 19.1 µm). The performance of the algorithm was represented by an area under the curve of 0.70 (p < 0.01). In conclusion, this study supports the association of a large blastocyst size with higher implantation potential and suggests that automatically measured blastocyst morphometrics can be used as a precise, consistent, and time-saving tool for improving blastocyst selection.

Prediction of oocyte maturation rate in the GnRH antagonist flexible IVF protocol using a novel machine learning algorithm - A retrospective study.

Oocyte maturation is affected by various patient and cycle parameters and has a key effect on treatment outcome. A prediction model for oocyte maturation rate formulated by using machine learning and neural network algorithms has not yet been described. A retrospective cohort study that included all women aged ≤ 38 years who underwent their first IVF treatment using a flexible GnRH antagonist protocol in a single tertiary hospital between 2010 and 2015. 462 patients met the inclusion criteria. Median maturation rate was approximately 80%. Baseline characteristics and treatment parameters of cycles with high oocyte maturation rate (≥80%, n = 236) were compared to cycles with low oocyte maturation rate (<80%, n = 226). We used an XGBoost algorithm that fits the training data using decision trees and rates factors according to their influence on the prediction. For the machine training phase, 80% of the cohort was randomly selected, while rest of the samples were used to evaluate our model's accuracy. We demonstrated an accuracy rate of 75% in predicting high oocyte maturation rate in GnRH antagonist cycles. Our model showed an operating characteristic curve with AUC of 0.78 (95% CI 0.73-0.82). The most predictive parameters were peak estradiol level on trigger day, estradiol level on antagonist initiation day, average dose of gonadotropins per day and progesterone level on trigger day. A state-of-the-art machine learning algorithm presented promising ability to predict oocyte maturation rate in the first GnRH antagonist flexible protocol using simple parameters before final trigger for ovulation. A prospective study to evaluate this model is needed.

Is there a relationship between morphokinetic parameters and neonatal sex in fresh embryo transfers?

To investigate whether morphokinetic parameters differ between male and female embryos in IVF embryos resulting in live births, a retrospective cohort study was undertaken. Files of all live births resulting from a single embryo transfer (SET) cultured in time-lapse incubators between 2013 and 2019 in two tertiary care centres were reviewed. The study group consisted of 187 SETs resulted in 187 live births, of which 100 were females (53.5%) and 87 were males (46.5%). Embryo selection for transfer was based on the known implantation data (KID) score provided by the Embryoscope and morphological assessment by experienced embryologists. Neonatal sex was confirmed through live birth documentation. Morphokinetic parameters and day 3 and day 5 KID scores of male and female embryos were compared. Maternal baseline and treatment characteristics were similar between groups. Morphokinetic time-lapse parameters of male and female embryos including: pronuclei fading; cleavage timings (t2-t9); second and third cell cycle durations; synchrony of the second and third cleavages; late morphokinetic parameters and KID scores did not differ between groups. In conclusion, time-lapse morphokinetic parameters and embryo selection methods do not seem to differ between male and female embryos, and their utilization does not bias towards any neonatal sex.

Correlations between antral follicle count and ultrasonographic ovarian parameters and clinical variables and outcomes in IVF cycles.

AIMS: To assess the correlation between the antral follicle count (AFC) and other ultrasonographic parameters and clinical variables in in vitro fertilization (IVF) cycles. METHODS: Pretreatment ultrasonographic evaluation included AFC (total), large (5-10 mm) and small (2-4 mm) antral follicles, ovarian volume, and ovarian Doppler indices. Data were prospectively uploaded and subsequently analysed in relation to IVF cycle results. RESULTS: The study included 128 women (128 cycles). Analysis of body mass index (BMI) yielded a weak significant correlation with large (5-10 mm) AFC but not with other sonographic variables. AFC was significantly correlated with patient age, ovarian volume, number of retrieved oocytes, total dose of used gonadotropins, peak estradiol, number of top-quality embryos, and number of frozen embryos and marginally correlated with number of aspirated immature oocytes. Lower large (5-10 mm) AFC was the only ovarian parameter associated with oral contraception pretreatment compared to nontreatment, even after adjustment for age and BMI. There was no difference in any of the parameters between short and long IVF cycles. CONCLUSIONS: BMI is only weakly correlated with AFC. Pretreatment with oral contraceptives may be associated with lower AFC. Pretreatment with gonadotropin-releasing hormone agonist (long protocol) does not alter the ultrasonographic ovarian parameters.

Severe combined immunodeficiency (SCID): from the detection of a new mutation to preimplantation genetic diagnosis.

PURPOSE: To describe the identification of a new mutation responsible for causing human severe combined immunodeficiency syndrome (SCID). In a large consanguineous Israeli Arab family, this served as a diagnostic tool and enabled us to carry out preimplantation genetic diagnosis (PGD). We also demonstrated that PGD for homozygosity alleles is feasible. METHODS: We carried out genome-wide screening followed by fine mapping and linkage analysis in order to identify the candidate genes. We then sequenced DCLRE1C in order to find the familial mutation. The family was anxious to avoid the birth of an affected child, and therefore, because of their religious beliefs, PGD was the only option open to them. The embryos were biopsied at day 3, and a single blastomere from each embryo was analyzed by multiplex polymerase chain reaction for the SCID mutation and 5 additional polymorphic markers flanking DCLRE1C. RESULTS: Linkage analysis revealed linkage to chromosome 10p13, which harbors the DNA Cross-Link Repair Protein 1 C (DCLRE1C) ARTEMIS gene. Sequencing identified an 8 bp insertion in exon 14 (1306ins8) of DCLRE1C in all the affected patients; this causes an alteration in amino acid 330 of the protein from cysteine to a stop codon (p.C330X). One cycle of PGD was performed and two embryos were transferred, one homozygous wild-type and one a heterozygous carrier, and healthy twins were born. CONCLUSIONS: Identifying the familial mutation enabled us to design a reliable and accurate PGD protocol, even in this case of a consanguineous family.

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.