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.

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.

Tubal superfetation following frozen-thawed single-embryo transfers in two separate cycles: Case report and literature review.

Superfetation is a very rare occurrence. In the context of assisted reproduction, it has been reported only as an intrauterine pregnancy after ovarian stimulation and/or embryo transfer in the presence of an undiagnosed ectopic pregnancy. Here we report a case of a 27-year-old anovulatory patient, gravida 1 para 1, who underwent two frozen-thawed single-blastocyst transfers in separate cycles. The patient reported that 12 days after the first transfer, she had menstrual bleeding and stopped her estradiol and progesterone supplementation without undergoing a blood human chorionic gonadotropin (ßhCG) test. At her request, a second cycle was immediately initiated, with endometrial thickness measuring 4 mm. Eleven days after the second transfer, the ßhCG value was inappropriately high. A right tubal pregnancy corresponding to 8 gestational weeks was diagnosed. Laparoscopy revealed a prominent right tubal pregnancy in addition to a significantly smaller left tubal pregnancy. The discordant tubal pregnancies were confirmed histologically. To our knowledge, superfetation involving a second ectopic pregnancy coexistent with a first, contralateral ectopic pregnancy consequent to consecutive in vitro fertilization procedures has not previously been described in the medical literature. This case emphasizes the importance of routine ßhCG testing after every IVF cycle, even if apparently unsuccessful.

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.

Estimating the effect of cesarean delivery on long-term childhood health across two countries.

Assessing the impact of cesarean delivery (CD) on long-term childhood outcomes is challenging as conducting a randomized controlled trial is rarely feasible and inferring it from observational data may be confounded. Utilizing data from electronic health records of 737,904 births, we defined and emulated a target trial to estimate the effect of CD on predefined long-term pediatric outcomes. Causal effects were estimated using pooled logistic regression and standardized survival curves, leveraging data breadth to account for potential confounders. Diverse sensitivity analyses were performed including replication of results in an external validation set from the UK including 625,044 births. Children born in CD had an increased risk to develop asthma (10-year risk differences (95% CI) 0.64% (0.31, 0.98)), an average treatment effect of 0.10 (0.07-0.12) on body mass index (BMI) z-scores at age 5 years old and 0.92 (0.68-1.14) on the number of respiratory infection events until 5 years of age. A positive 10-year risk difference was also observed for atopy (10-year risk differences (95% CI) 0.74% (-0.06, 1.52)) and allergy 0.47% (-0.32, 1.28)). Increased risk for these outcomes was also observed in the UK cohort. Our findings add to a growing body of evidence on the long-term effects of CD on pediatric morbidity, may assist in the decision to perform CD when not medically indicated and paves the way to future research on the mechanisms underlying these effects and intervention strategies targeting them.

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

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

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

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

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

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

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.

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 relationship between resited epidural catheters after secondary epidural catheter failure and vaginal delivery: A retrospective case-control study.

BACKGROUND: There are cases where epidural analgesia is initially effective but subsequently fails and needs to be resited. We evaluated the rate of normal vaginal delivery and operative delivery among parturients who had resited epidurals compared to parturients with epidurals that were not resited. METHODS: A retrospective electronic medical review of parturients with a singleton gestation attempting normal vaginal delivery under epidural analgesia between the years 2012-2016 was conducted. Resited epidurals were defined as epidurals that were considered effective but subsequently removed and reinserted. For each resited epidural, two previous and two consecutive deliveries of parturients with normally functioning epidural catheter inserted by the same anesthesiologist were matched controls (non-resited epidurals). RESULTS: There were 35,984 attempted vaginal deliveries with 118 resited epidurals and 472 non-resited epidurals. When adjusted for nulliparity, oxytocin administration, sex and weight of the baby, and maternal BMI, labor epidural catheter replacement was not associated with need for instrumental or caesarean delivery, (OR 1.5, 95% CI 0.91-2.49, P = .11). CONCLUSIONS: Need for labor epidural catheter replacement does not appear to be associated with need for operative delivery based on this single-centre cohort analysis.

[PLACENTAL BED RESEARCH - UNDERSTANDING THE PATHOPHYSIOLOGY OF THE GREAT OBSTETRICAL SYNDROMES].

INTRODUCTION: Research on the placenta bed - the interface between the mother and the fetus, substantially contributed to the understanding of the pathophysiology of the so-called great obstetrical syndromes (preeclampsia, fetal growth restriction, preterm labor, placental abruption). The physiological modifications of the utero-placental spiral arteries was the key finding, thereafter, many other unique physiological and pathophysiological changes were discovered, specifically related to these clinical syndromes. In the current issue, a group of researchers from the Edith Wolfson's Obstetrics and Gynecology Department present their lengthy experience in placental bed histopathological research in various clinical syndromes such as preeclampsia, preterm delivery and fetal growth restriction. In addition, a unique study using the dual-perfused single cotyledon model was performed to evaluate the effects of MgSO4 and Labetalol on placental blood vessel reactivity in response to angiotensin II. This outstanding collaboration between clinical and histopathological researchers should be encouraged and hopefully performed in many other medical centers.

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.

Novel extra cellular-like matrices to improve human ovarian grafting.

PURPOSE: To investigate if human ovarian grafting with pure virgin human recombinant collagen type-1 from bioengineered plant lines (CollPlant™) or small intestine submucosa (SIS) yields better implantation results for human ovarian tissue and which method benefits more when combined with the host melatonin treatment and graft incubation with biological glue + vitamin E + vascular endothelial growth factor-A. METHODS: Human ovarian tissue wrapped in CollPlant or SIS was transplanted into immunodeficient mice with/without host/graft treatment. The tissue was assessed by follicle counts (including atretic), for apoptosis evaluation by terminal deoxynucleotidyl transferase assay and for immunohistochemical evaluation of neovascularization by platelet endothelial cell adhesion molecule (PECAM) expression, and for identification of proliferating granulosa cells by Ki67 expression. RESULTS: Human ovarian tissue transplanted with CollPlant or SIS fused with the surrounding tissue and promoted neovascularization. In general, implantation with CollPlant even without additives promoted better results than with SIS: significantly higher number of recovered follicles, significantly fewer atretic follicles, and significantly more granulosa cell proliferation. Moreover, results with CollPlant alone seemed to be at least as good as those after host and graft treatments. CONCLUSIONS: CollPlant is a biomaterial without any potential risks, and grafting ovarian tissue with CollPlant is easy and the procedure may be easily modified, with limited or no foreseeable risks, for auto-transplantation in cancer survivors. Further studies are needed using other novel methods capable of enhancing neovascularization and reducing apoptosis and follicle atresia.

[PROSPECTIVE INVESTIGATION OF POSTOPERATIVE NAUSEA AND VOMITING FOLLOWING DUAL PROPHYLAXIS AND LOW DOSE NEURAXIAL MORPHINE FOR CESAREAN DELIVERY].

BACKGROUND: Spinal morphine provides the optimal treatment for post-cesarean analgesia, despite frequent nausea and vomiting. We investigated the incidence of nausea and vomiting 24 hours after cesarean delivery in women receiving intrathecal morphine 100 µcg and intravenous prophylactic dexamethasone and ondansetron. METHODS: In a prospective, observational, Institutional Review Board (IRB) approved study of women undergoing cesarean delivery according to a standardized anesthetic protocol, the subjects were approached preoperatively and underwent standardized interviews regarding prior anesthesia experience and history of postoperative nausea and vomiting. In the post anesthesia care unit and 24 hours postoperatively, the women were interviewed regarding the incidence of nausea and vomiting, Women with and without nausea at 24 hours were compared for potential associated risk factors. RESULTS: Among 201 women recruited, 29 (14.5%) had nausea and 7 (3.5%) vomited in the postoperative care unit. During the first 24 hours, 36 (17.9%) had experienced nausea and 19 (9.5%) had vomited when interviewed at the 24-hours postoperatively. Women who had nausea 24 hours postoperatively were more likely to have nausea in the post anesthesia care unit than women without nausea during 24 hours after cesarean delivery (41.7% versus 1.2%, p<0.001). We did not find preoperative risk factors for postoperative nausea and vomiting. CONCLUSIONS: We report that almost 20% of the women managed with prophylactic dual therapy of ondansetron and dexamethasone had nausea during the 24 hours after administration of low dose intrathecal morphine. Our findings suggested that women who experience nausea or vomiting in the immediate postoperative period are at increased risk of nausea and vomiting in the 24-hour postoperative period.

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.

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.