High prevalence of low prognosis by the POSEIDON criteria in women undergoing planned oocyte cryopreservation.

OBJECTIVE: Planned oocyte cryopreservation (OC) is being increasingly utilized worldwide. However, some women cannot accumulate sufficient oocytes because of poor response to stimulation. The POSEIDON classification is a novel system to classify patients with 'expected' or 'unexpected' inappropriate ovarian response to exogenous gonadotropins. Our study aimed to examine the prevalence of POSEIDON patients among women undergoing planned OC. STUDY DESIGN: We retrospectively reviewed the first cycles of 160 consecutive patients undergoing planned OC. Patients were classified into the four POSEIDON groups or as 'non-POSEIDON' based on age, AMH level and the number of oocytes retrieved. The primary outcome measure was the prevalence of POSEIDON patients. RESULTS: Overall, 63 patients (39.4 %) were classified as POSEIDON patients, 12 in group 1, 12 in group 2, 8 in group 3, and 31 in group 4. Compared to non-POSEIDON patients, POSEIDON patients had increased basal FSH levels and reduced serum AMH levels and antral follicle counts, required higher FSH starting doses and increased gonadotropin requirements and reached lower peak serum estradiol levels. Additionally, POSEIDON patients had a lower number of oocytes retrieved (7.6 ± 3.1 vs.20.2 ± 9.9, p < 0.001) and vitrified (5.8 ± 2.9 vs.14.7 ± 6.8, p < 0.001) than non-POSEIDON counterparts, respectively. CONCLUSION: We found a high prevalence of patients being classified as low prognosis according to the POSEIDON criteria among patients seeking planned OC. POSEIDON patients had increased gonadotropin requirements and a significantly lower number of oocytes retrieved and vitrified. This novel, unexpected finding adds clinically relevant information for counselling and management of patients undergoing planned OC.

Placenta previa in in vitro fertilization and unassisted pregnancies-is there a difference in perinatal outcomes and placental histology?

INTRODUCTION: In-vitro-fertilization (IVF) is an independent risk factor for placenta previa (PP). Our aim was to study this link by comparing the clinical characteristics and placental histology of pregnancies complicated by PP in IVF versus unassisted pregnancies. METHODS: A retrospective-cohort study of deliveries with PP between 2008 and 2021. Placental histology, obstetric and neonatal outcomes were compared between IVF and unassisted pregnancies. Included, were singleton deliveries complicated by PP at gestational weeks (GA) >24. RESULTS: A total of 182 pregnancies were included - 23 IVF pregnancies (IVF group) and 159 unassisted pregnancies (Control group). The control group was characterized by higher gravidity (p = .007) and parity (p < .001) and a trend of more past cesarean deliveries, whereas the IVF group- by a higher rate of nulliparity (p < .001) and diabetes mellitus (p = .04). The control group was characterized by a higher rate of placental weight below the 10th percentile (47.8 versus 13.9%, p = .001) and by a trend of a lower overall placental weight. No differences were noted in maternal and fetal vascular lesions. DISCUSSION: While PP in non-assisted pregnancies is probably associated with previous CDs, in IVF it is more "sporadic," and may complicate any index pregnancy. A lower placental weight was more prevalent in the control group, supporting the concept that pregnancies complicated by PP following IVF can be attributed to initial abnormal location of placentation, rather than an underlying pathological uterine segment of implantation. Nevertheless, IVF and unassisted pregnancies entail similar perinatal outcomes in cases of PP.

Obstetric and Perinatal Outcomes following Ovulation Induction and Unassisted Pregnancies in the Same Mother.

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: · Ovulation induction entails lower birthweight.. · This may relate to supraphysiological hormonal levels.. · Monitoring fetal growth is advised in such cases..

The effect of SARS-CoV-2 mRNA vaccination on AMH concentrations in infertile women.

RESEARCH QUESTION: Does SARS-CoV-2 mRNA vaccination affect the ovarian reserve of infertile women undergoing IVF? DESIGN: This was a prospective observational study at a single university-affiliated IVF unit that included infertile women aged 18-44 years who were undergoing IVF/intracytoplasmic sperm injection between November 2020 and September 2021, had received two doses of SARS-CoV-2 mRNA vaccination and had undergone measurement of baseline anti-Müllerian hormone (AMH) concentration within the 12 months preceding their recruitment. AMH concentrations before and after vaccination were evaluated and compared. RESULTS: Overall, 31 women were included in the study. The median AMH concentrations before and after COVID-19 vaccine were comparable (1.7 versus 1.6 g/ml, respectively, P = 0.96). No correlation was found between the participant's anti-COVID-19 antibody titre and the change in AMH concentration. CONCLUSIONS: SARS-CoV-2 mRNA vaccination does not adversely affect ovarian reserve, as shown by comparing serum AMH concentrations before and after vaccination. These findings may serve as a counselling tool for clinicians to reassure women undergoing fertility treatment that SARS-CoV-2 mRNA vaccination is safe.

Obstetric outcomes following ovarian hyperstimulation syndrome in IVF - a comparison with uncomplicated fresh and frozen transfer cycles.

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.

Obstetric and Perinatal Outcomes of Pregnancies Resulting from Fresh Versus Frozen Embryo Transfer-a Sibling Cohort.

We aimed to compare obstetric and perinatal outcomes of in vitro fertilization (IVF) pregnancies following fresh and frozen embryo transfer (FET). This was a historic cohort of deliveries between November 2008 and January 2020 at a single university hospital, in which each fresh transfer IVF pregnancy was matched to a FET pregnancy by the same woman (1:1 ratio). We included live singleton deliveries (> 24 weeks of gestation) and excluded pregnancies following egg donation. The primary outcome was birthweight, and secondary outcomes were small for gestational age (SGA) neonates and preterm birth (PTB). A total of 107 fresh transfer pregnancies were matched to 107 FET pregnancies, in the same women. Mean maternal age was lower in the fresh transfer group compared to the FET group (30.4 vs. 32.5 years, p < 0.001). A higher rate of nulliparity was noted in fresh transfer pregnancies (64.5% vs. 12.1%, p < 0.001). Mean birthweight was non-significant between the groups (p = 0.13), and the rates of low birthweight and small for gestational age neonates did not differ between the groups. Preterm deliveries occurred in 10.3% and 9.3% of fresh transfer and FET pregnancies respectively, p = 0.79. On multivariate linear regression analysis, the type of embryo transfer-FET or fresh-was not independently associated with birthweight, after adjustment for women's age, nulliparity, and BMI. IVF pregnancies following fresh and FET entailed the same obstetric and perinatal outcomes when compared in the same women.

Prediction, assessment, and management of suboptimal GnRH agonist trigger: a systematic review.

PURPOSE: This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa triggering, and available options for prevention and management of suboptimal response. METHODS: PubMed, Google Scholar, Medline, and the Cochrane Library were searched for keywords related to GnRHa triggering, and peer-reviewed articles from January 2000 to September 2021 included. RESULTS: Thirty-seven studies were included in the review. A suboptimal response to GnRHa triggering was more likely following long-term or recent oral contraceptive use and with a low or high body mass index. Low basal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol serum levels were correlated with suboptimal oocyte yield, as was a low serum LH level on the day of triggering. A prolonged stimulation period and increased gonadotropin requirements were correlated with suboptimal response to triggering. Post-trigger LH < 15 IU/L best correlated with an increased risk for empty follicle syndrome and a lower oocyte retrieval rate. Retriggering with hCG may be considered in patients with suboptimal response according to post-trigger LH, as in cases of failed aspiration. CONCLUSION: Pre-treatment assessment of patient characteristics, with pre- and post-triggering assessment of clinical and endocrine cycle characteristics, may identify cases at risk for suboptimal response to GnRHa triggering and optimize its utilization.

Can endocrine characteristics of early pregnancy following natural cycle cryopreserved embryo transfer predict live birth?

RESEARCH QUESTION: Can serial measurements of serum oestradiol, progesterone and ß-human chorionic gonadotrophin (HCG) concentrations, starting from the day of the first positive pregnancy test, predict live birth after natural cycle frozen-thawed embryo transfer (NC-FET)? DESIGN: This was a historical cohort study of women with a positive pregnancy test following NC-FET, between March 2009 and January 2020. Serum ß-HCG, oestradiol and progesterone concentrations were measured on the day of the first pregnancy test and 48 and 96 h later. Pregnancies resulting in a live birth were compared with non-viable pregnancies. RESULTS: Of 101 women with a positive pregnancy test included in the study, 78 had a live birth and 23 had a non-viable pregnancy. Serum ß-HCG concentrations were comparable on the day of the first pregnancy test (P = 0.09) but became significantly higher in women with a live birth 48 and 96 h later (P = 0.018 and P = 0.003). Serum oestradiol concentrations were higher in women with a live birth at all three measurements (P = 0.02, P = 0.007 and P = 0.02). Serum progesterone concentrations were higher 48 h after the first pregnancy test in women with a live birth (P = 0.04). On multivariate analysis, after controlling for the women's ages and number of embryos transferred, serum concentrations above the 25th percentile for oestradiol (>488-526 pmol/L) and progesterone (>63-70 nmol/L) were independent predictors of live birth at all three measurements. CONCLUSIONS: Increased serum oestradiol and progesterone concentrations in early NC-FET pregnancies are associated with increased likelihood of live birth. Oestradiol and progesterone concentrations can be used in conjunction with ß-HCG to predict pregnancy viability and assist in patient counselling.

Gestational diabetes mellitus in in-vitro fertilization pregnancies - Clinical and placental histological characteristics.

INTRODUCTION: We aimed to investigate obstetric and neonatal outcomes and placental histological findings in in vitro fertilization (IVF) pregnancies complicated by gestational diabetes mellitus (GDM) as compared to unassisted pregnancies. METHODS: This was a retrospective cohort of deliveries at a single university affiliated center between 12/2008 and 01/2020. Included were singleton pregnancies complicated by GDM, for which placental histopathological examination was performed. Obstetric, neonatal and placental outcomes were compared between pregnancies following IVF and unassisted pregnancies. Placental lesions were categorized according to the "Amsterdam" criteria. RESULTS: Included were 688 deliveries with a diagnosis of GDM with placental examination - 69 IVF pregnancies (IVF group) and 619 unassisted pregnancies (control group). The IVF group was characterized by a significantly higher maternal age and higher rate of nulliparous women - 60.8% vs. 32.9%, p < 0.001. There were no differences in GDM type between the study groups - about two thirds of cases were GDMA1 and on third GDMA2. A higher incidence of preeclampsia was noted in the IVF group - 17.3% vs. 9.3%, p = 0.03, with no difference in cesarean deliveries and birthweight. IVF deliveries were characterized by a significantly higher rate of adverse neonatal outcomes - 18.8% vs. 8.8%, p = 0.008, although this did not attain significance after adjustment to gestational age. No differences were noted in placental histology between the groups. DISCUSSION: GDM in IVF is associated with a significantly higher rate of adverse neonatal outcomes, as compared with non-assisted pregnancies complicated by GDM. Placental histology does not shed light on these clinical associations.

Should women receive luteal support following natural cycle frozen embryo transfer? A systematic review and meta-analysis.

BACKGROUND: Spontaneous ovulation during a natural menstrual cycle is frequently used for timing frozen embryo transfer (FET). Nevertheless, it remains unclear whether or not women should receive luteal phase support (LPS) following natural cycle frozen embryo transfer (NC-FET). OBJECTIVE AND RATIONALE: The aim of this systematic review and meta-analysis was to study whether the administration of LPS improves the reproductive outcome following NC-FET. SEARCH METHODS: We conducted a systematic search of the literature published in Medline/PubMed, Embase and the Cochrane Library, from January 2000 until December 2020. We included all original English, peer-reviewed articles, irrespective of the study design. The search strategy included keywords related to NC-FET and luteal phase support. Studies reporting the results of artificial or stimulated FET cycles were excluded. OUTCOMES: Our systematic search generated 416 records. After screening, eight studies were included in the review and seven studies were included in the meta-analysis. Two studies (n = 858) used hCG and six studies (n = 1507) used progesterone for luteal support. Four studies were randomised controlled trials (RCTs), whereas the other four were historic cohort studies. In a meta-analysis using a random effects model, hCG administration for LPS did not increase the clinical pregnancy rate (CPR) (two studies, odds ratio (OR) 0.85, 95% CI 0.64-1.14). On the other hand, progesterone LPS was associated with a higher CPR (five studies, OR 1.48, 95% CI 1.14-1.94), and a higher live birth rate (LBR) (three studies, OR 1.67, 95% CI 1.19-2.36). The association between progesterone LPS and the LBR remained significant after excluding non-randomised studies. WIDER IMPLICATIONS: The available evidence indicates that progesterone administration for LPS is beneficial following NC-FET. There is no evidence to support the administration of hCG for LPS in these cases. Additional large RCTs are necessary to improve the quality of evidence and validate our findings.

Misoprostol treatment for early pregnancy loss: an international survey.

RESEARCH QUESTION: What is the global variability in misoprostol treatment for the management of early pregnancy loss (EPL)? DESIGN: An international web-based survey of fertility specialists and obstetrics and gynaecology clinicians was conducted between August and November 2020. The survey consisted of 16 questions addressing several aspects of misoprostol treatment for EPL. RESULTS: Overall, 309 clinicians from 80 countries participated in the survey, of whom 67.3% were fertility specialists. Nearly one-half (47.9%) of the respondents let the patient choose the first line of treatment (expectant management, misoprostol treatment or surgical aspiration) according to her own preference. The 248 respondents who administer misoprostol in their daily practice were asked further questions; 59.7% of them advise patients to take the medication at home. The most common dose and route of administration is 800 µg administered vaginally. Only 28.6% of participants use mifepristone pretreatment. Variation in the timing of the first follow-up visit after misoprostol administration was wide, ranging from 24 h to 1 week in most clinics. In case of incomplete expulsion, only 42.3% of the respondents routinely administer a second dose. The timing of the final visit and the definition of successful treatment also differed greatly among respondents. CONCLUSIONS: There is large variability in the use of misoprostol for the management of EPL. High-quality research is necessary to examine several aspects of the treatment. Particularly, the timing and effectiveness of a second dose administration and the criteria to decide on treatment failure or success deserve more research in the future.

Placental disorders of pregnancy in subsequent IVF pregnancies - a sibling cohort.

RESEARCH QUESTION: To assess whether the incidence of placental disorders of pregnancy decreases with increasing parity in repeat IVF pregnancies, in the same way as natural pregnancies. DESIGN: This was a retrospective cohort of deliveries between November 2008 and January 2020, in a single university-affiliated medical centre. The study included women with only IVF-attained singleton pregnancies (no natural conception) with at least two deliveries, and compared the obstetric and perinatal outcomes between first, second and third deliveries. Each woman served as her own control. The primary outcome was the incidence of placental-related disorders of pregnancy, defined as small for gestational age (SGA) neonates and/or pre-eclampsia. RESULTS: A total of 307 first deliveries, 307 second deliveries and 49 third deliveries by the same women were compared. A trend for a decreased rate of pre-eclampsia was noted with increased parity (P = 0.06) and a significant decrease in the rate of SGA: 11.7% for first delivery, 7.8% for second delivery and 2.0% for third (P = 0.04). This difference in SGA incidence was maintained in a matched sub-analysis of the 49 women with three deliveries (P = 0.04), and after adjustment for fresh/frozen embryo transfer (P = 0.03). Although SGA and pre-eclampsia were generally more common in IVF than natural pregnancies, their decrease with increasing parity mimicked that in natural pregnancies. CONCLUSION: IVF pregnancies are associated with an increased risk of placental disorders of pregnancy. However, they exhibit a decrease in incidence with increasing parity.

A randomized controlled trial of vaginal progesterone for luteal phase support in modified natural cycle - frozen embryo transfer.

OBJECTIVE: Our aim was to study whether luteal phase support (LPS) increases the live-birth rate (LBR) in women undergoing modified natural cycle (mNC) frozen-thawed embryo transfer (FET). METHODS: In a randomized controlled trial, conducted at a university-affiliated tertiary medical center, a total of 59 patients aged 18-45 years, underwent mNC-FET. FET was performed in mNC following ovulation triggering by hCG. Patients were randomized into two groups; The No-LPS Group included 28 women who did not receive LPS, and the LPS Group included 31 women who received vaginal progesterone for LPS. The main outcome measure was LBR. RESULTS: Baseline demographic and clinical characteristics were comparable between the study groups. The no-LPS group and the LPS group did not differ with regard to clinical pregnancy rate (21.4% vs. 32.3%; respectively, p = .35), LBR (17.9% vs. 19.4%; respectively, p = .88), or spontaneous miscarriage rate (3.6% vs. 12.9%; respectively, p = .35). On multivariate logistic regression analysis, LPS was not associated with LBR after controlling for confounders. CONCLUSION: The results of our study suggest that LPS after mNC-FET does not improve the reproductive outcome, and therefore, might not be necessary.C linicaltrials.gov identifier: NCT01483365.

Complications of the third stage of labor in in vitro fertilization pregnancies: an additional expression of abnormal placentation?

OBJECTIVE: To assess the correlation between in vitro fertilization (IVF) and complications of the third stage of labor. DESIGN: Retrospective cohort of vaginal deliveries from November 2008 to January 2020. Maternal and obstetric outcomes of singleton deliveries were compared between IVF and non-IVF pregnancies. SETTING: University hospital. PATIENT(S): Women with live singleton vaginal deliveries at >24 weeks of gestation. INTERVENTION(S): In vitro fertilization-attained pregnancies (compared with spontaneous ones). MAIN OUTCOME MEASURE(S): Complications of the third stage of labor, defined as manual placental removal (either entire removal due to nonseparation or exploration of the uterine cavity due to suspected retained products of conception). RESULT(S): Overall, 1,264 IVF pregnancies and 34,166 non-IVF pregnancies were included. Deliveries in the IVF group were characterized by an older maternal age, lower parity, higher rate of diabetes and hypertensive disorders, higher rate of placental abnormalities, earlier gestational age, higher rate of labor induction, chorioamnionitis, and instrumental delivery. Complications of the third stage of labor occurred in 5.9% of IVF deliveries and in 2.8% of controls, and blood transfusion was more prevalent in IVF deliveries. The rate of complications of the third stage were higher in both fresh and frozen transfer cycles as compared with spontaneous pregnancies (5.8%, 8.8%, and 2.8%, respectively), although no difference was noted between fresh and frozen transfers. In vitro fertilization was associated independently with complications of the third stage of labor after adjustment for potential confounders. CONCLUSION(S): In vitro fertilization is associated independently with an increased risk of complications of the third stage of labor.

Obstetric and perinatal outcomes of in vitro fertilization and natural pregnancies in the same mother.

OBJECTIVE: To compare obstetric and perinatal outcomes between pregnancies conceived using in vitro fertilization (IVF) and natural pregnancies of the same women. DESIGN: This was a case-control study of deliveries between November 2008 and January 2020 in which each IVF pregnancy was matched to a natural pregnancy of the same woman (1:1 ratio). SETTING: University hospital. PATIENT(S): We included women with consecutive live singleton deliveries (>24 weeks of gestation) at the Edith Wolfson Medical Center. We excluded IVF pregnancies attained using egg donation. INTERVENTION(S): In vitro fertilization-attained pregnancies (as compared with natural ones). MAIN OUTCOME MEASURE(S): Primary outcome: preterm birth (PTB). SECONDARY OUTCOMES: small for gestational age (SGA) neonates and pregnancy-induced hypertension (PIH; gestational hypertension or pre-eclampsia). RESULT(S): A total of 544 IVF pregnancies were matched to 544 natural pregnancies, each in the same woman. In 292 women (53.7%), the natural pregnancy preceded the IVF pregnancy. Maternal age was significantly higher in IVF deliveries. Gestational age at delivery and the rates of PTB, PIH, instrumental delivery, cesarean delivery, and SGA neonates were comparable between IVF and natural pregnancies. Birth weight was slightly lower in IVF pregnancies. On multivariate analysis, IVF was not independently associated with PTB, SGA, or PIH after adjustment for confounders. CONCLUSION(S): When compared in a cohort of the same women, natural and IVF-attained pregnancies did not differ with regard to obstetric and perinatal outcomes.

Does the interval between the last GnRH antagonist dose and the GnRH agonist trigger affect oocyte recovery and maturation rates?

RESEARCH QUESTION: Does the time interval between the last gonadotrophin-releasing hormone (GnRH) antagonist dose and the GnRH agonist trigger affect the efficacy of the trigger in IVF treatments? DESIGN: This retrospective cohort study involved 53 normogonadotrophic patients undergoing GnRH antagonist-based IVF cycles, in a single academic centre between June 2019 and February 2020, in whom a GnRH agonist was used for final ovulation triggering. RESULTS: The mean time interval between the last GnRH antagonist dose and GnRH agonist triggering was 4.6 ± 2.7 h (range 1-12 h). There was no correlation between the antagonist-agonist interval and the oocyte recovery rate (Spearman's correlation coefficient [CC] 0.02, P = 0.89) or metaphase II oocyte rate (CC 0.006, P = 0.96). On multivariate analysis, the antagonist-agonist interval was not associated with treatment outcomes, after adjusting for the women's age and body mass index. CONCLUSIONS: This is the first study assessing the efficacy of the GnRH agonist trigger in relation to the time interval between the last GnRH antagonist dose and the agonist trigger within the first half-life of the GnRH antagonist and in less than 12 h. In normogonadotrophic patients, a GnRH agonist trigger can successfully induce an effective LH surge and oocyte maturation and release, irrespective of the time interval between the last antagonist dose and the agonist trigger. Once confirmed by randomized clinical trials, these finding may simplify treatment, improve patients' convenience and promote patient adherence to treatment.

Reproductive outcome after early pregnancy loss treated with misoprostol versus surgical aspiration.

RESEARCH QUESTION: Does long-term reproductive outcome after early pregnancy loss (EPL) differ between women who are treated with misoprostol and surgical aspiration. DESIGN: A historic cohort study of all women who were diagnosed with early pregnancy loss (≤12 weeks), in a single medical centre, between September 2016 and August 2017, was conducted. The women were treated with either misoprostol or surgical aspiration according to their own preferences. Women who were lost to follow-up or did not attempt to conceive again were excluded. The primary outcome measure was the cumulative pregnancy rate within 12 months from intervention. RESULTS: Baseline characteristics were comparable between women who received misoprostol (n = 163) and women who underwent surgical aspiration (n = 122). Women who received misoprostol had a higher rate of interventions for retained products of conception (11.0% versus 3.3%, respectively; P = 0.015). The misoprostol and the surgical aspiration groups did not differ in rate of repeated miscarriages (17.8% versus 21.3%, respectively; P = 0.45), or pregnancy rate within 6 months (58.3% versus 50.0%, respectively; P = 0.16), 12 months (78.5% versus 78.7%, respectively; P = 0.97) and 24 months (92.0% versus 91.8%, respectively; P = 0.94). Live birth rate within 24 months was comparable (62.0% versus 58.2%, respectively; P = 0.52), as well as gestational age at birth (38.5 versus 38.6 weeks, respectively; P = 0.81) and birthweight (3295 versus 3161 g, respectively; P = 0.07). CONCLUSIONS: Long-term reproductive outcomes are comparable in women with EPL who are treated with either misoprostol or surgical aspiration. Our findings may help counselling patients facing EPL who have concerns about their future reproduction.

Placental-related disorders of pregnancy and IVF: does placental histological examination explain the excess risk?

RESEARCH QUESTION: What are the clinical characteristics of pregnancies complicated by fetal growth restriction (FGR) and preeclampsia in patients who have undergone IVF, and what is the correlation between these complications and histopathological placental findings in such pregnancies. DESIGN: A retrospective cohort of patients who had delivered their babies at our institution who had been diagnosed with preeclampsia, whose babies had been diagnosed with FGR, or both. Deliveries in which the placenta was sent for histopathological examination were included. Computerized files and pathological reports were reviewed, and maternal, obstetric, neonatal outcomes and placental histopathological reports were compared between pregnancies conceived by IVF and controls. Placental lesions were classified according to the Amsterdam criteria. RESULTS: Between December 2008 and December 2018, the placentas of 1114 singleton babies who had received a diagnosis of FGR, whose mothers had received a diagnosis of preeclampisa, or both, were examined. A total of 105 patients conceived with IVF and 1009 were conceived spontaneously. The IVF group was older, of lower parity and had a higher rate of diabetes and chronic hypertension. Deliveries occurred at an earlier gestational age, although birth weight was not significantly different between the groups. The rate of neonatal adverse composite outcome among IVF deliveries was significantly lower (59.0% versus 76.7%; P < 0.001). On placental examination, placental weight, maternal and fetal vascular malperfusion lesions were similar between the groups, whereas villitis of unknown etiology was significantly more common among the IVF group (16.2% versus 8.3%; P = 0.007). CONCLUSION: Neonatal outcome is relatively favourable in IVF patients with placental-related diseases. Placental chronic villitis is more common in IVF patients, pointing to an additive immunological cause.

Placental histopathology in IVF pregnancies resulting from the transfer of frozen-thawed embryos compared with fresh embryos.

PURPOSE: To study whether placentas of singleton pregnancies conceived after fresh embryo transfer (ET) contain more histopathological lesions compared with placentas of singleton pregnancies conceived after frozen-thawed embryo transfer (FET). METHODS: A prospective cohort study of placental histopathology in 131 women with singleton IVF pregnancies who delivered at a single medical center, between December 2017 and May 2019. The prevalence of different placental histopathology lesions was compared between women who conceived after fresh ET and FET. RESULTS: Women who conceived after fresh ET (n = 74) did not differ from women who conceived after FET (n = 57) with regard to maternal age, BMI, nulliparity, or infertility diagnosis. Gestational week at delivery was lower in pregnancies conceived after fresh ET (38.5 vs. 39.2 weeks, respectively, p = 0.04), and a trend for a lower birthweight following fresh ET was noted (3040 vs. 3216 g, respectively, p = 0.053). However, placental histopathology analysis from pregnancies conceived after fresh ET was comparable to pregnancies conceived after FET, with regard to the prevalence of maternal vascular malperfusion lesions (45.9% vs. 50.9%, respectively, p = 0.57), fetal vascular malperfusion lesions (17.6% vs. 21.1, p = 0.61), acute inflammatory response lesions (28.4% vs. 28.1%, respectively, p = 0.96), and chronic inflammatory response lesions (13.5% vs. 8.8%, respectively, p = 0.48). CONCLUSION: Placental histopathology did not differ between IVF pregnancies conceived after fresh and frozen ET. These results are reassuring for clinicians and patients who wish to pursue with transferring fresh embryos.

Ovarian stimulation for freeze-all IVF cycles: a systematic review.

BACKGROUND: Freeze-all IVF cycles are becoming increasingly prevalent for a variety of clinical indications. However, the actual treatment objectives and preferred treatment regimens for freeze-all cycles have not been clearly established. OBJECTIVE AND RATIONALE: We aimed to conduct a systematic review of all aspects of ovarian stimulation for freeze-all cycles. SEARCH METHODS: A comprehensive search in Medline, Embase and The Cochrane Library was performed. The search strategy included keywords related to freeze-all, cycle segmentation, cumulative live birth rate, preimplantation genetic diagnosis, preimplantation genetic testing for aneuploidy, fertility preservation, oocyte donation and frozen-thawed embryo transfer. We included relevant studies published in English from 2000 to 2018. OUTCOMES: Our search generated 3292 records. Overall, 69 articles were included in the final review. Good-quality evidence indicates that in freeze-all cycles the cumulative live birth rate increases as the number of oocytes retrieved increases. Although the risk of severe ovarian hyperstimulation syndrome (OHSS) is virtually eliminated in freeze-all cycles, there are certain risks associated with retrieval of large oocyte cohorts. Therefore, ovarian stimulation should be planned to yield between 15 and 20 oocytes. The early follicular phase is currently the preferred starting point for ovarian stimulation, although luteal phase stimulation can be used if necessary. The improved safety associated with the GnRH antagonist regimen makes it the regimen of choice for ovarian stimulation in freeze-all cycles. Ovulation triggering with a GnRH agonist almost completely eliminates the risk of OHSS without affecting oocyte and embryo quality and is therefore the trigger of choice. The addition of low-dose hCG in a dual trigger has been suggested to improve oocyte and embryo quality, but further research in freeze-all cycles is required. Moderate-quality evidence indicates that in freeze-all cycles, a moderate delay of 2-3 days in ovulation triggering may result in the retrieval of an increased number of mature oocytes without impairing the pregnancy rate. There are no high-quality studies evaluating the effects of sustained supraphysiological estradiol (E2) levels on the safety and efficacy of freeze-all cycles. However, no significant adverse effects have been described. There is conflicting evidence regarding the effect of late follicular progesterone elevation in freeze-all cycles. WIDER IMPLICATIONS: Ovarian stimulation for freeze-all cycles is different in many aspects from conventional stimulation for fresh IVF cycles. Optimisation of ovarian stimulation for freeze-all cycles should result in enhanced treatment safety along with improved cumulative live birth rates and should become the focus of future studies.