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.

Clinical significance of true umbilical cord knot: a propensity score matching study.

OBJECTIVE: True umbilical cord knot (TUCK) is a rare finding that often leads to intensified surveillance and patient anxiety. This study sought to evaluate the incidence, risk factors, and obstetric and neonatal outcomes of TUCK. METHODS: A retrospective cohort study was conducted at a tertiary university medical center in 2007-2019. Patients with singleton pregnancies diagnosed postnatally with TUCK were identified and compared to women without TUCK for obstetric and neonatal outcomes using propensity score matching (PSM). RESULTS: TUCK was diagnosed in 780 of the 96,766 deliveries (0.8%). Women with TUCK were older than those without TUCK (32.57 vs. 31.06 years, P < 0.001) and had higher gravidity (3 vs. 2, P < 001) and a higher rate of prior stillbirth (1.76% vs. 0.43%, P < 0.01). Following covariate adjustment, 732 women with TUCK were compared to 7320 matched controls. TUCK was associated with emergency cesarean delivery due to non-reassuring fetal heart rate (2.54% vs. 4.35%, P = 0.008, OR 1.71, 95%CI 1.14-2.56) and intrapartum meconium-stained amniotic fluid (19.26% vs. 15.41%, P = 0.022, OR 1.31, 95%CI 1.04-1.65). Neonatal outcomes were comparable except for higher rates of 1-min Apgar score < 7 and neonatal seizures in the TUCK group. The stillbirth rate was higher in the TUCK group, but the difference was not statistically significant (1.23% vs 0.62%, P = 0.06, OR 1.96, 95%CI 0.96-4.03). CONCLUSIONS: TUCK has several identifiable risk factors. Pregnant women with TUCK may cautiously be informed of the relatively low risks of major obstetric or perinatal complications. The lower occurrence of stillbirth in the TUCK group warrants further study.

Single men's attitudes towards posthumous use of their sperm cryopreserved due to illness in Israel.

BACKGROUND: Banking of frozen spermatozoa by single men opens the possibility of procreation long after their death. Requests for posthumous reproduction by the families of the deceased are growing, raising an ethical debate, especially when written instructions were not left by the patients and in cases of unplanned perimortem collection. The issue of the progenitors' intention to procreate after death is the key to ethically based decision-making in these cases. OBJECTIVES: To evaluate the attitude of single men cryopreserving spermatozoa before life-threatening medical situations towards post-mortem usage of their cryopreserved spermatozoa. MATERIALS & METHODS: Adult single men prior to sperm cryopreservation before cytotoxic therapy were asked to sign a structured form declaring their will and instructions for the usage of their cryopreserved spermatozoa in case of their demise. RESULTS: Four hundred fifty-two men of diverse ethnicity, religious and cultural backgrounds signed the form providing instructions for the use of their cryopreserved spermatozoa in case of mortality. Their age was 27.4 ± 8.06 years. Seven (1.5%) patients willed their spermatozoa for posthumous reproduction to a sibling, 22 (4.9%) to parents, and 26 (5.7%) to their informal female partners. The significant majority (n = 397; 87.8 %) of the single men were ordered to destroy their cryopreserved spermatozoa in case of their expiry. Note that, 26-39 years old men were less likely (81.8% vs. >90% in other ages) to order sperm destruction, as well as men with a poorer prognosis (83% vs. 90%). DISCUSSION: In this study group, most single men cryopreserving spermatozoa in the face of future life-threatening morbidity do so for their own future live parenthood, and are not interested in posthumous reproduction. CONCLUSION: Our results doubt the claim that single men who had an unplanned perimortem sperm collection can be universally presumed to have wished to father a child posthumously. Any claimed assumed consent in these cases should be considered for each case individually based on its specific circumstances.

Is There an Age Limit for a Trial of Vaginal Delivery in Nulliparous Women?

BACKGROUND: The number of nulliparous women over the age of 35 is consistently increasing, and the optimal delivery strategy is a subject of ongoing discussion. This study compares perinatal outcomes in nulliparous women aged ≥35 years undergoing a trial of labor (TOL) versus a planned cesarean delivery (CD). METHODS: A retrospective cohort study including all nulliparous women ≥ 35 years who delivered a single term fetus at a single center between 2007-2019. We compared obstetric and perinatal outcomes according to mode of delivery-TOL versus a planned CD, in three different age groups: (1) 35-37 years, (2) 38-40 years, and (3) >40 years. RESULTS: Out of 103,920 deliveries during the study period, 3034 women met the inclusion criteria. Of them, 1626 (53.59%) were 35-37 years old (group 1), 848 (27.95%) were 38-40 (group 2), and 560 (18.46%) were >40 years (group 3). TOL rates decreased as age increased: 87.7% in group 1, 79.3% in group 2, and 50.1% in group 3, p < 0.001. Rates of successful vaginal delivery were 83.4% in group 1, 79.0% in group 2, and 69.4% in group 3, p < 0.001). Neonatal outcomes were comparable between a TOL and a planned CD. Using multivariate logistic regression, maternal age was found to be independently associated with slightly increased odds for a failed TOL (aOR = 1.13, CI 95% 1.067-1.202). CONCLUSIONS: A TOL at advanced maternal age appears to be safe, with considerable success rates. As maternal age advances, there is a small additive risk of intrapartum CD.

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.

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.

Route of postpartum oxytocin administration and maternal hemoglobin decline - A randomized controlled trial.

OBJECTIVE: Oxytocin uterotonic agents are routinely administered during the third stage of labor, however, the administration route is varying, intravenously or intramuscularly. We aimed to compare the effect of different regimens of postpartum oxytocin administration on hemoglobin (Hb) and hematocrit (Hct) decline. METHODS: A randomized, 3-arm study of women who delivered vaginally at term in a single tertiary medical center was conducted. Immediately following the delivery of the fetus women randomly received one of 3 oxytocin regimens: 1) intramuscular 10units (IM group); 2) intravenous 10units in 100 ml 0.9%NaCl solution over 10-15 min (IV group); or 3) combined IV + IM regimens (IV + IM group). Primary outcome was defined as the level of Hb decline between prepartum and postpartum measurements. RESULTS: Overall, 210 women (70 in each group) were randomized, with 171 included in the final analysis (IM group-61, IV group-57, IV + IM group-53). There was no significant difference between the groups regarding maternal age, pre-pregnancy body-mass-index (BMI), parity, operative vaginal deliveries rate, the rate of episiotomy or perineal tears or neonatal birthweight. Mean prepartum Hb and Hct level were 12.3 ± 1.1 g/dl and 36.9 ± 2.7%, respectively, with no significant difference between the groups. Mean postpartum HB and Hct decline was 1.3 ± 0.8 g/dl and 3.7 ± 2.3%, respectively, with no difference between the groups. In multivariable analysis after adjusting for parity, pre-pregnancy BMI, labor induction, episiotomy or perineal tears and neonatal birthweight, oxytocin regimen was not associated with any difference in hematological measurements. CONCLUSION: Postpartum Hb and Hct decline was usually minor following vaginal deliveries, and was not affected by postpartum oxytocin regimen.

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.

Amniocentesis in twin gestation: the association between gestational age at procedure and complications.

PURPOSE: Third trimester amniocentesis is often performed when indications arise after 24 weeks of gestation-typically to investigate new sonographic findings, and might be related to pre-term birth. Scarcity of data exists concerning the risks of third-trimester amniocentesis in twin pregnancies. METHODS: A retrospective cohort study of all twin gestations that underwent amniocentesis in a tertiary hospital between 2007 and 2016. Outcomes and procedure-related complications were compared between third-trimester (≥ 24 weeks) and mid-trimester amniocentesis (16-23 weeks). Primary outcome was defined as membrane rupture within four weeks of procedure. Logistic regression analysis was utilized to adjust results to potential confounders. RESULTS: Overall, 185 eligible women were included, of them, 28 (15.1%) underwent third-trimester amniocentesis and 157 (84.9%) underwent mid-trimester amniocentesis. Women in the third-trimester amniocentesis group were younger and presented higher frequencies of intra-uterine growth restriction (31.5 vs. 35.3, p < 0.001, and 28% vs. 10% p = 0.015, respectively). The prevalence of membrane rupture within 4 weeks of the procedure was significantly higher in the third-trimester amniocentesis group (31% vs. 1%, p < 0.001). Delivery rates after third-trimester amniocentesis within 1, 2 and 4 weeks of the procedure were 11%, 14.8% and 52%, respectively, versus 0% following mid-trimester amniocentesis (p < 0.001). Gestational age at delivery was similar between the groups (35.7 vs. 36.4 gestational weeks, p = 0.34). In multivariate analysis, gestational age at amniocentesis was found to be an independent risk factor for premature rupture of membranes within 4 weeks of the procedure. CONCLUSION: Third trimester amniocentesis in twin pregnancies is associated with significantly higher rates of procedure-related membrane rupture compared to mid-trimester amniocentesis.

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

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

Does the time interval from the end of sperm processing to intrauterine insemination (lab-to-uterus time) affect treatment outcome?

BACKGROUND: Intra-uterine insemination is an essential component in the treatment of infertility. Success rates are dependent on clinical factors of the female partner, sperm quality, and preparation technique. The effect of the time interval between the end of sperm preparation in the lab, and its injection into the uterine cavity (lab-to-uterus time) is yet to be determined. AIM: To investigate the association between the lab-to-uterus time and the pregnancy rate. MATERIALS AND METHODS: Partner and donor spermatozoa intra-uterine insemination cycles were included. Preparation for intra-uterine insemination of partners' fresh ejaculate or donor thawed spermatozoa was identical. The time interval from the completion of this stage to the actual intra-uterine injection was recorded. The lab-to-uterus intervals were divided into groups A (0-29 min), B (30-59 min), C (60-89 min), and D (90-180 min). Pregnancy was defined as two adequate consecutive doubling levels of hCG and the pregnancy rates were compared between the groups. RESULTS: A total of 267 female patients (138 partner spermatozoa, 129 donors) who had 470 intra-uterine insemination cycles (218 partner spermatozoa, 252 donors) were included. No significant differences in pregnancy rates per treatment cycle were found between the four lab-to-uterus interval groups: A (n = 96 cycles; 16.7%), B (n = 217; 19.4%), C (n = 121; 16.5%), and D (n = 36; 36.1%). No difference was found in the pregnancy rates between partner and donor spermatozoa. In the case of fresh partner spermatozoa, the pregnancy rates for groups were as follows: A (n = 40 cycles, 20%); B (n = 94; 14.9%), C (n = 70; 17.1%), and D (n = 14; 35.7%) (NS). In the case of thawed donor spermatozoa, the pregnancy rates (per cycle) for groups were as follows: A (n = 56; 14.3%), B (n = 123; 22.8%), C (n = 51; 15.7%), and D (n = 22; 36.4)% (NS). CONCLUSIONS: The intra-uterine insemination outcome was not affected by the lab-to-uterus time interval. Extended waiting up to 3 h for insemination did not have any detrimental effect on pregnancy rates, regardless if partner or donor spermatozoa was used.

Generation of vascular chimerism within donor organs.

Whole organ perfusion decellularization has been proposed as a promising method to generate non-immunogenic organs from allogeneic and xenogeneic donors. However, the ability to recellularize organ scaffolds with multiple patient-specific cells in a spatially controlled manner remains challenging. Here, we propose that replacing donor endothelial cells alone, while keeping the rest of the organ viable and functional, is more technically feasible, and may offer a significant shortcut in the efforts to engineer transplantable organs. Vascular decellularization was achieved ex vivo, under controlled machine perfusion conditions, in various rat and porcine organs, including the kidneys, liver, lungs, heart, aorta, hind limbs, and pancreas. In addition, vascular decellularization of selected organs was performed in situ, within the donor body, achieving better control over the perfusion process. Human placenta-derived endothelial progenitor cells (EPCs) were used as immunologically-acceptable human cells to repopulate the luminal surface of de-endothelialized aorta (in vitro), kidneys, lungs and hind limbs (ex vivo). This study provides evidence that artificially generating vascular chimerism is feasible and could potentially pave the way for crossing the immunological barrier to xenotransplantation, as well as reducing the immunological burden of allogeneic grafts.

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.

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.

New predictors of early impaired placentation preceding miscarriage before 10 weeks of gestation in IVF pregnancies: A prospective study.

INTRODUCTION: In a recent study of 10,011 pregnant women, 95% of miscarriages occurred before routine ultrasound scan at 11-14 weeks. Our study aimed to identify early first trimester parameters which may predict miscarriage before 10 weeks of gestation for in vitro fertilization (IVF) pregnancies. METHODS: A cohort of 115 healthy IVF patients with a singleton viable embryo in early first trimester were studied in a tertiary university-affiliated medical center (April 2017-June 2018). Calculations included gestational age (GA); ultrasound evaluation of crown-rump length (CRL), mean gestational sac diameter (GSD) and volume (GSV), mean yolk sac diameter (YSD) and volume (YSV); fetal heart rate (FHR), mean uterine arteries pulsatility index (UtA-PI); and maternal blood placental protein 13 (PP13) levels. Patients were divided into three groups by GA; and early miscarriage versus ongoing pregnancy after GA 10 weeks. RESULTS: Early fetal loss occurred in 14.8% of patients; miscarriage group had higher discrepancy between calculated and measured GA (P < 0.001), lower GSD and GSV (P = 0.005 and P = 0.02, respectively), significantly different YSD and YSV, and lower GSD/YSD and GSV/YSV ratios (P = 0.001 and P = 0.003, respectively). UtA-PI/CRL ratio was higher in patients with miscarriage at GA 46-48 days and GA >48 days (P = 0.034 and P = 0.026, respectively). PP13/CRL ratio was higher in patients with miscarriage at GA >48 days (P = 0.041). DISCUSSION: In IVF pregnancies with live embryo at first ultrasound scan, high UtA-PI/CRL and maternal blood PP13/CRL ratios may indicate impaired placentation preceded early pregnancy loss. A larger cohort is needed to further verify these predictions.

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.

The effect of meconium-stained amniotic fluid on perinatal outcome in pregnancies complicated by preterm premature rupture of membranes.

PURPOSE: To determine whether meconium-stained amniotic fluid (MSAF) encountered in pregnancies complicated by preterm premature rupture of membranes (PPROM) is associated with adverse maternal and perinatal outcome. METHODS: A retrospective cohort study of all singleton pregnancies with PPROM and MSAF who delivered in a tertiary hospital at 24 + 0-36 + 6 weeks of gestation between 2007 and 2017. Women with PPROM-MSAF (study group) were compared to women with PPROM and clear amniotic fluid (control group). Controls were matched to cases according to age, gravidity, parity and gestational age at delivery in a 3:1 ratio. Primary outcome was defined as neonatal intensive care unit admission. Secondary outcomes were neonatal adverse outcomes, chorioamnionitis and placental abruption diagnosed clinically or by placental cultures and histology. RESULTS: Seventy-five women comprised the study group and were matched to 225 women representing the control group. A significantly higher rate of neonatal intensive care unit admissions was noted in the study group compared to controls (61.3% vs. 45.7%, p = 0.03). Multivariate analysis demonstrated that MSAF is an independent risk factor for neonatal intensive care unit admission (adjusted OR = 2.82, 95% CI 1.39-5.75, p = 0.004). MSAF was found to be associated to higher rates of cesarean and operative vaginal deliveries (30.7% vs. 24.4% and 5.3% vs. 2.7%, p = 0.057, respectively) as well as to chorioamnionitis and placental abruption (33.3% vs. 19.3%, p = 0.034 and 16.0% vs. 7.7%, p = 0.021, respectively). CONCLUSION: MSAF is associated with higher frequencies of adverse perinatal outcome when compared to clear amniotic fluid in pregnancies complicated by PPROM.