Hadas Ganer Herman

BACKGROUND: There has been an increase in the average age of patients seeking fertility treatments over the past decades, with a significantly higher rate of advanced maternal age (AMA) patients undergoing IVF. It is unclear if different treatment strategies in IVF improve outcomes in AMA patients. OBJECTIVE AND RATIONALE: The aim of this systematic review was to assess the efficacy of different interventions employed in IVF in patients of AMA. SEARCH METHODS: A comprehensive search in Embase, Medline, and the Cochrane Library was performed. The search strategy included keywords related to IVF and AMA. We included all original peer-reviewed articles published in English, from January 1985 to September 2024, primarily designed to assess the efficacy of different interventions in IVF on clinical outcomes in AMA patients. Meta-analyses were performed for interventions for which sufficient randomized controlled trials existed. OUTCOMES: A total of 151 studies were included in the review. AMA was not consistently defined in all studies reviewed, although common to all studies was an age above 35 years. For the majority of evidence, there appeared to be no clear advantage to any stimulation protocol in AMA patients. There also appeared to be no advantage to any specific FSH medication, while a meta-analysis performed for the addition of LH to follicular stimulating hormone in stimulation demonstrated similar clinical pregnancy and live birth rates. No good evidence was found to support the routine implementation of ICSI in AMA patients, while a meta-analysis performed for assisted hatching (AH) pointed to decreased live birth rates with its implementation. Low-quality evidence demonstrated an increase in live birth rates with multiple embryos transferred with an increase in multiple pregnancies delivered. Finally, a meta-analysis performed for preimplantation genetic testing for aneuploidy (PGT-A) pointed to similar live birth rates as for no testing. WIDER IMPLICATIONS: This review failed to find an advantage to the routine implementation of treatment strategies such as specific stimulation protocols and gonadotropins, ICSI, and PGT-A, and a potential harmful effect for AH. Future high-quality randomized controlled trials are needed to affirm the majority of this review’s conclusions. REGISTRATION NUMBER: PROSPERO ID: CRD42022335889.

Objective We aimed to assess whether ovulation induction treatments affect obstetric and neonatal outcomes. Study Design This was a historic cohort study of deliveries in a single university-affiliated medical center between November 2008 and January 2020. We included women who had one pregnancy following ovulation induction and one unassisted pregnancy. The obstetric and perinatal outcomes were compared between pregnancies following ovulation induction and unassisted pregnancies, so that each woman served as her own control. The primary outcome measure was birth weight. Results A total of 193 deliveries following ovulation induction and 193 deliveries after unassisted conception by the same women were compared. Ovulation induction pregnancies were characterized by a significantly younger maternal age and a higher rate of nulliparity (62.7 vs. 8.3%, p < 0.001). In pregnancies achieved by ovulation induction, we found a higher rate of preterm birth (8.3 vs. 4.1%, p = 0.02) and instrumental deliveries (8.8 vs. 2.1%, p = 0.005), while cesarean delivery rates were higher following unassisted pregnancies. Birth weight was significantly lower in ovulation induction pregnancies (3,167 ± 436 vs. 3,251 ± 460 g, p = 0.009), although the rate of small for gestational age neonates was similar between the groups. On multivariate analysis, birth weight remained significantly associated with ovulation induction after adjustment for confounders, while preterm birth did not. Conclusion Pregnancies following ovulation induction treatments are associated with lower birth weight. This may be related to an altered placentation process following uterine exposure to supraphysiological hormonal levels. Key Points

Introduction and objective: This cross-sectional study aimed to compare the prevalence of urinary symptoms in physically active females to the general population represented by medical staff. Materials and methods: We conducted a survey utilizing the UDI-6 questionnaire on women playing catchball for at least one year and training twice a week or more in an official Israeli competitive league. The control group consisted of women practicing medicine (physicians and nurses). Results: The study group consisted of 317 catchball players and the control group consisted of 105 medical staff practitioners. Both groups were similar in most of the demographic characteristics. Urinary symptoms represented by UDI-6 scores were higher in women in the catchball group. Frequency and urgency symptoms were common in women playing catchball. Stress urinary incontinence (SUI) was insignificant between the groups (43.8% in the catchball group and 35.2% in the medical staff group, p = 0.114). However, severe symptoms of SUI were more common in catchball players. Conclusions: The rates of all urinary symptoms were higher in in catchball players. SUI symptoms were common in both groups. However, severe symptoms of SUI were more common in catchball players.

Do obstetric outcomes and placental findings in pregnancies conceived with IVF vary according to embryo quality? Pregnancies following the transfer of lower-quality embryos were associated with a higher rate of low-lying placentas and several adverse placental lesions. A few studies have shown reduced pregnancy and live births rates with poor-quality embryo transfer, yet with comparable obstetric outcomes. None of these studies included placental analysis. A retrospective cohort study of 641 deliveries of IVF attained pregnancies between 2009 and 2017 was carried out. Live singleton births after IVF with a single blastocyst transfer at a university-affiliated tertiary hospital were included. Excluded were cycles of oocyte recipients and IVM. We compared pregnancies following the transfer of a poor-quality blastocyst (poor-quality group) or a good-quality blastocyst (controls, good-quality group). During the study period, all placentas from complicated and uncomplicated pregnancies were sent to pathology. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes, adjusted for diminished ovarian reserve, fresh versus frozen transfer, and neonatal gender (as indicated by univariable analysis). A total of 132 deliveries in the poor-quality group were compared to 509 controls. A diagnosis of diminished ovarian reserve was more common in the poor-quality group than in the control group (14.3% versus 5.5%, respectively, P < 0.001) and more pregnancies in the poor-quality group were following frozen embryo transfer. After adjustment for confounders, poor-quality embryos were associated with a higher rate of low-lying placentas [adjusted odds ratio (aOR) 2.35, 95% CI 1.02–5.41, P = 0.04] and placentas with a higher rate of villitis of unknown etiology (aOR 2.97, 95% CI 1.17–6.66, P = 0.02), distal villous hypoplasia (aOR 3.78, 95% CI 1.20–11.38, P = 0.02), intervillous thrombosis (aOR 2.41, 95% CI 1.39–4.16, P = 0.001), multiple maternal malperfusion lesions (aOR 1.59, 95% CI 1.06–2.37, P = 0.02), and parenchymal calcifications (aOR 2.19, 95% CI 1.07–4.46, P = 0.03). The study is limited by its retrospective design and the utilization of two grading systems during the study period. In addition, the sample size was limited to detect differences in outcomes of rarer occurrences. The placental lesions demonstrated in our study imply an altered immunological response to the implantation of poor-quality embryos. Yet, these findings were not associated with additional adverse obstetric outcomes and merit reaffirmation in a larger cohort. Overall, the clinical findings of our study are reassuring to clinicians and patients for whom the transfer of a poor-quality embryo is necessary. No external funding was obtained for this study. The authors declare no conflict of interest, N/A.

Purpose To assess perinatal outcomes and placental findings in in vitro fertilization (IVF) patients with previous recurrent pregnancy loss (RPL). Methods This was a retrospective cohort of live singleton births following IVF at a single university–affiliated center between 2009 and 2017. Outcomes were compared between patients with previous RPL, defined as two miscarriages (RPL group), and patients without RPL (control group). Placental examination was performed for all deliveries irrelevant of complications, and findings categorized according to the Amsterdam Placental Workshop Consensus. Results One hundred seventy-two deliveries of women with previous RPL (RPL group) were compared to 885 controls. Maternal age, 36.2 ± 4.2 vs. 35.4 ± 4.2 years, p = 0.02, and rate of uterine fibroids, 12.7% vs. 7.3%, p = 0.01, were higher in the RPL group. The rate of nulliparity was lower in the RPL group, 63.3% vs. 74.1%, p = 0.003. Unexplained infertility and diminished ovarian reserve were more common in the RPL group and male factor infertility in controls. There was a lower rate of fresh embryo transfer in the RPL group, 50.5% vs. 64.7%, p < 0.001, and reduced endometrial thickness. Similar obstetric outcomes were noted in the groups after adjustment for confounders. Placental examinations were notable for lower placental thickness, β − 0.17 cm, 95%CI − 0.30–(− 0.0), a lower rate of velamentous cord insertion, aOR 0.44, 95%CI 0.20–0.95, and a higher rate of villous infarction, aOR 2.82, 95%CI 1.28–6.20 in the RPL group. Conclusion In IVF patients with a history of RPL, subsequent deliveries were associated with a limited number of placental lesions, yet with similar obstetric outcomes.

Background: We aimed to assess the correlation between ovarian hyperstimulation syndrome (OHSS) in the early course of in vitro fertilization (IVF) pregnancies and obstetric outcomes. Methods: We identified records of patients admitted due to OHSS following IVF treatment at our institution between 2008 and 2020. Cases were included if pregnancy resulted in a live singleton delivery (OHSS group). OHSS cases were matched at a 1:5:5 ratio with live singleton deliveries following IVF with fresh embryo transfer (fresh transfer group) and frozen embryo transfer (FET group), according to maternal age and parity. Computerized files were reviewed, and maternal, obstetric and neonatal outcomes compared. Results: Overall, 44 OHSS cases were matched with 220 fresh transfer and 220 FET pregnancies. Patient demographics were similar between the groups, including body mass index, smoking and comorbidities. Gestational age at delivery, the rate of preterm births, preeclampsia and cesarean delivery were similar between the groups. Placental abruption occurred in 6.8% of OHSS pregnancies, 1.4% of fresh transfer pregnancies and 0.9% of FET pregnancies (p=0.02). On post-hoc analysis, the rate of placental abruption was significantly higher in OHSS pregnancies, compared with the two other groups, and this maintained significance after adjustment for confounders. Birthweights were 3017 ± 483, 3057 ± 545 and 3213 ± 542 grams in the OHSS, fresh transfer and FET groups, respectively (p=0.004), although the rate of small for gestational age neonates was similar between the groups. Conclusions: OHSS in the early course of IVF pregnancies is associated with an increased risk of placental abruption.

Are deliveries following IVF with a thinner endometrium associated with adverse perinatal outcomes and placental findings? Live births following IVF with a thinner endometrium are associated with an increased rate of placental-mediated obstetric complications and lower birthweight, while the placentas are notable for gross anatomical and histological malperfusion lesions. Past studies have noted a higher rate of adverse outcomes on deliveries following IVF with a thinner endometrium, mainly placental-associated complications. However, no study to date has investigated placental histopathology in such cases. This was a retrospective cohort study of 1057 deliveries following IVF, between 2009 and 2017. All placentas were sent to pathology irrelevant of pregnancy complication status, per protocol at our institution. Live singleton births from a tertiary university hospital after IVF were compared between patients for whom embryo transfer was performed with an endometrium P = 0.003. Higher rates of fresh transfers were noted in the control group, while the thinner endometrium group was notable for higher rates of blastocyte transfers. After adjustment for confounders, deliveries in the thinner endometrium group were associated with an overall higher rate of main placental-mediated complications, 22.9% versus 15.2%, P = 0.003, and significantly lower birthweight, β −100.76 g (−184.4–(−17.0)). Placentas in the thinner endometrium group were notable for reduced thickness and a higher rate of bilobated placentas. Placental histology in the thinner endometrium group demonstrated a higher rate of maternal malperfusion lesions. The study was limited by its retrospective design and lack of data regarding prior uterine surgery. In addition, sample size was limited for detection of differences in outcomes of rarer occurrence and for analysis as per a stricter definition of thin endometrium. Excess obstetric risks should be taken into consideration while planning an embryo transfer with a thinner endometrium. Further studies are needed to assess the yield of cycle cancellation and the effect of potential preventive measures such as Micropirin treatment. No funding was used and the authors report no conflicting interests. N/A.