Obstetrical and neonatal outcomes of IVF twins after fresh embryo transfer versus frozen-thawed embryo transfer.

Objectives The limited data regarding obstetrical outcomes in multiple pregnancies following both fresh embryo transfer and frozen-thawed embryo transfer (FET), along with the association between multiple pregnancies and increased pregnancy complications compared to singleton pregnancies, highlights the need for research on this topic. Therefore, this study aimed to compare obstetrical and neonatal outcomes of twin pregnancies after fresh embryo transfer versus FET. Design A retrospective single-center study. Participants IVF dichorionic twin pregnancies ≥23 weeks of gestation during 2010-2022. Setting Galilee Medical Center, a tertiary-care university affiliated hospital, Israel. Methods We conducted a comparative analysis of obstetrical and neonatal outcomes between IVF dichorionic twin pregnancies after fresh embryo transfer and those after FET. This analysis included variables such as gestational age at delivery, birthweight, preterm birth rates, low birthweight rates, neonatal intensive care unit admissions and complications related to prematurity. Results The study included 389 IVF twin pregnancies: 253 after fresh embryo transfer and 136 after FET. Following fresh embryo transfer compared to FET, the mean gestational age at delivery was earlier (34.92 vs. 35.88 weeks, p=0.001) and the rate of preterm birth (<37 weeks) was higher (70.4% vs. 53.7%, p=0.001). This difference in gestational age at delivery remained significant after adjustment for maternal age, parity, and BMI (OR=2.11, 95% CI 2.11-3.27, p=0.001). Similarly, the difference in preterm birth rates remained significant after adjustment of the same variables (p=0.001). For the fresh embryo transfer compared to the FET group, the mean birthweight was lower (2179.72 vs. 2353.35 grams, p=0.003); and low birthweight and very low birthweight rates were higher (71.2% vs. 56.3%, p<0.001 and 13.5% vs. 6.7%, p=0.004, respectively). For the fresh embryo transfer compared to the FET group, the proportions were higher of neonates admitted to the neonatal intensive care unit (23.3% vs. 16.0%, p=0.019), of neonates with respiratory distress syndrome (10.5% vs. 5.9%, p=0.045) and those needing phototherapy (23.3% vs. 16.0%, p=0.019). Limitations Limitations of the study include its retrospective nature. Furthermore, we were unable to adjust for some confounders, such as the number of eggs retrieved, the number of embryos transferred, and methods for ovarian stimulation or preparation of the endometrium for embryo transfer. Conclusions Obstetrical and neonatal outcomes of twin pregnancies were worse after fresh embryo transfer than after FET. The findings support favorable fetal outcomes after FET and support the current trend of shifting from fresh embryo transfer to FET. Prospective studies are needed to support our results.

Same-day Discharge after Robotic Hysterectomy for Benign Conditions: Feasibility and Safety.

STUDY OBJECTIVE: To investigate the feasibility and predictive factors for same-day discharge (SDD) after robotic hysterectomy (RH) for benign indications to optimize patient selection by incorporating preoperative, intraoperative, and postoperative variables. DESIGN: A single-center retrospective cohort study. SETTING: Tertiary academic hospital. PATIENTS: Patients undergoing RH for benign indications. INTERVENTIONS: Patients were designated for SDD by implementing enhanced recovery after surgery protocol. MEASUREMENTS AND MAIN RESULTS: The study included 890 patients who underwent RH for benign indications between the years 2016 and 2021. Of these, 618 (69.4%) were discharged the same day and 272 (30.5%) were admitted for overnight stay. Both groups had similar age (46.4 vs 46.2 years), body mass index (28.3 vs 28.9), and indications for surgery. In multivariable logistic regression, factors that were significant for overnight stay were American Society of Anesthesiologists score 3, Charlson comorbidity index, previous laparotomy, and operative time. Other factors such as surgery start time and preoperative hemoglobin levels were not statistically significant. Postoperative outcomes were comparable for both groups with similar readmission and reoperation rates. CONCLUSION: The likelihood of SDD after RH in this cohort after implementing enhanced recovery after surgery protocol was almost 70%, and most of the predictive factors for overnight stay were nonmodifiable. Importantly, both groups had similar outcomes after surgery.

Effect of uterine dimensions on live birth rates after single embryo transfer in infertile women.

RESEARCH QUESTION: Do uterine size parameters measured by baseline transvaginal ultrasound predict live birth after single embryo transfer (SET) of a high-quality blastocyst? DESIGN: Retrospective cohort study including women undergoing their first SET between August 2010 and March 2014 at a large university hospital reproductive centre. The effects of baseline uterine dimensions on live birth rate (LBR) were analysed while controlling for confounding effects. RESULTS: A total of 437 nulliparous and 70 parous women were included. The nulliparous group had lower body mass index (BMI) (24.4 ± 5.1 versus 25.9 ± 4.5 kg/m2; P = 0.015) and a higher number of fibroids (0.4 ± 1.0 versus 0.2 ± 0.5; P = 0.005) than the parous group. While controlling for confounding effects, none of the uterine parameters appeared to be a significant predictor of LBR among nulliparous and parous women (P > 0.05 in all cases). A subsequent analysis of endometrial length was done, whereby the endometrial lengths were divided into quartiles (20.0-32.2 mm; 32.3-36.5 mm; 36.6-40.0 mm; 40.1-54.0 mm). After controlling for confounders, the shortest quartile in the nulliparous group had a significantly lower LBR (P = 0.02) than the other groups. Receiver operating characteristic curves suggested that endometrial cavity length and cervical length did not aid clinically. CONCLUSION: Uterine parameters do not have a clinically useful impact on LBR after SET of a blastocyst in infertile women. The use of baseline endometrial length to predict live birth is no better than chance, while cervical length only predicts failure to live birth.

A comparison of IVF outcomes transferring a single ideal blastocyst in women with polycystic ovary syndrome and normal ovulatory controls.

PURPOSE: To assess the effects PCOS on live birth rates when transferring a single fresh ideal blastocyst. METHODS: A retrospective cohort study performed at the university-affiliated reproductive center. Women with PCOS and a control group of normal ovulatory women who underwent their first fresh embryo transfer with single ideal grade blastocyst were included in the study. Demographic, stimulation information and pregnancy outcomes were collected and analysed. The primary outcome was live birth rates, and secondary outcomes included pregnancy and clinical pregnancy rates. RESULTS: 71 Women with PCOS and 272 normal ovulatory controls underwent their first embryo transfer and met the inclusion and exclusion criteria. PCOS patient were younger (31.0 ± 3.7 vs. 33.1 ± 3.2, p = 0.0001), with higher AFC (40.0 ± 9.3 vs. 13.3 ± 4.6, p = 0.0001), required lower dose of gonadotropins to stimulate (1198 ± 786 vs. 1891 ± 1224, p = 0.0001), and had higher serum testosterone levels (2.3 ± 0.7 vs. 1.1 ± 0.3, p = 0.0001). No significant difference was found between the two groups regarding the number of previous pregnancies, the number of previous full-term pregnancies, the level of basal serum FSH, estradiol level at triggering and the BMI. When compared by Chi squared testing pregnancy rates, clinical pregnancy rates and live birth rates did not differ. However, when controlling (with multivariate stepwise logistic regression) for confounders, live birth rates were lower among the women with PCOS (p = 0.035, CI: 0.18-0.92). CONCLUSION: After controlling for confounders, when transferring a fresh single ideal blastocyst, live birth rates were lower among the women with PCOS than normal ovulatory controls.

Fresh transfer of Day 5 slow-growing embryos versus deferred transfer of vitrified, fully expanded Day 6 blastocysts: which is the optimal approach?

STUDY QUESTION: In IVF cycles in which the entire embryo cohort is slow growing, is it optimal to perform fresh transfer in Day 5 or to extend the culture and transfer in subsequent vitrified-warmed cycles? SUMMARY ANSWER: The outcomes depend on the degree of embryo development on Day 5. WHAT IS KNOWN ALREADY: Slow-growing blastocysts have lower implantation potential when transferred in fresh cycles. It has been suggested that embryo-endometrial asynchrony could explain this finding. However, studies that compared Days 5 and 6 embryos in frozen embryo transfer (FET) cycles showed contradictory results. There is still a lack of evidence regarding the best approach, performing fresh transfer or deferring transfer and continuing culture until fully developed blastocysts are achieved, when the entire cohort of embryos is slow growing. STUDY DESIGN SIZE, DURATION: This was a retrospective study that included 477 women aged <40 years who underwent fresh Day 5 single embryo transfer of slow-growing embryos and subsequent FET cycles of fully expanded blastocysts (FEB) originating from the same IVF cycle between 2012 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included cycles in which the embryos either began blastulation by Day 5 of culture but did not reach the fully expanded stage (Gardner Stage III) or had delayed blastulation with only morula embryos present by Day 5 of culture. All of the subjects in the study underwent elective, single embryo transfer (slow or delayed blastocysts) on Day 5 and had at least one embryo that developed into a FEB on extended culture Day 6 that was suitable for vitrification. All subjects, regardless of the outcome of the fresh transfer, returned for at least one subsequent FET cycle of Day 6 embryos. MAIN RESULTS AND ROLE OF CHANCE: A total of 1070 embryo transfer cycles (fresh + FET) were included. Of them, 365 women had elective, fresh, single transfer of slow-growing blastocysts (Group I) and 112 had elective, fresh, single morula transfer (Group II). Groups I and II underwent a subsequent 457 and 136 FET cycles, respectively. The mean age of Group I was 33.8 ± 2.9 years, the proportion of Day 5 embryos that developed to FEB by Day 6 was 92%, and the number of blastocysts vitrified was 627 (average of 1.71 blastocysts per cycle). The outcomes of fresh and FET cycles were comparable regarding clinical pregnancy rate (CPR) (31.0 vs. 30.4%, P = 0.86) and live birth rate (LBR) (23.3 vs. 20.3%, P = 0.15). In Group II, the mean age was 35.8 ± 3.4 years and the proportion of morula embryos that developed to FEB by Day 6 was 72%. The number of blastocysts vitrified on Day 6 was 155 (1.38 per cycle). The transfer of fresh embryos in Group II resulted in significantly lower clinical pregnancy (5.3 vs. 30.1%, P < 0.001) and LBRs (1.8 vs. 20.5%, P < 0.001). The results did not change after controlling for possible confounding factors. LIMITATIONS AND REASONS FOR CAUTION: The retrospective design of the study is a major limitation. Although we compared the outcomes of embryos that originated from the same cohort, the FET cycles could have been overrepresented by older patients and those with poorer prognoses. Furthermore, the study included only cycles in which there were blastocysts available for cryopreservation on Day 6; therefore, the results were not be applicable for those who had mandatory Day 5 transfer with no embryos available for vitrification. WIDER IMPLICATIONS OF THE FINDINGS: Fresh transfer of embryos that begin blastulation on Day 5 results in similar outcomes to the transfer of FEB originating from the same cohort. However, in cases where only morula/compacting embryos are available by Day 5, extending culture until FEB are achieved and then performing subsequent FET will result in significantly higher LBRs. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

A comparison of two months pretreatment with GnRH agonists with or without an aromatase inhibitor in women with ultrasound-diagnosed ovarian endometriomas undergoing IVF.

RESEARCH QUESTION: Does the addition of an aromatase inhibitor improve IVF outcomes in women with endometriomas when pretreating them with gonadotrophin-releasing hormone agonists? DESIGN: Retrospective two-centre cohort study involving 126 women aged 21-39 years who failed a previous IVF cycle and all subsequent embryo transfers and had sonographic evidence of endometriomas. Women were non-randomly assigned to either 3.75 mg intramuscular depo-leuprolide treatment alone or in combination with 5 mg of oral letrozole daily for 60 days prior to undergoing a fresh IVF cycle. Main outcome measures included clinical pregnancy rate and ongoing pregnancy rate after 24 weeks' gestation. RESULTS: Prior to treatment, antral follicle count (AFC), basal serum FSH and endometrioma diameter did not differ between groups. After treatment, AFC differed between letrozole and non-letrozole-treated groups (10.3 ± 2.0 versus 6.4 ± 2.5; P = 0.0001), as did mean endometrioma maximum diameter (1.8 ± 0.4 cm versus 3.2 ± 0.8 cm; P = 0.0001). At IVF, the gonadotrophin dose used was significantly lower in letrozole-treated subjects (2079 ± 1119 versus 3716 ± 1314; P = 0.0001), the number of mature oocytes collected was greater (9.1 ± 2.4 versus 4.0 ± 1.7; P = 0.0001), as were the number of two-pronuclear embryos and number of blastocysts. The clinical pregnancy rate was significantly higher in the letrozole-treated group (50% versus 22%, P = 0.003), as was the live birth rate (40% versus 17%, P = 0.008). CONCLUSIONS: The combination of depo-leuprolide acetate monthly for 60 days combined with daily letrozole has better clinical outcomes at IVF in women with endometriomas than depo-leuprolide acetate treatment alone.

Use of cabergoline and post-collection GnRH antagonist administration for prevention of ovarian hyperstimulation syndrome.

RESEARCH QUESTION: Does the addition of a gonadotrophin-releasing hormone (GnRH) antagonist to cabergoline treatment during the luteal phase in fresh IVF cycles triggered with a GnRH agonist, and planned for freeze-all, reduce the rate of mild and moderate ovarian hyperstimulation syndrome (OHSS)? DESIGN: Retrospective cohort study of 480 IVF patients at risk for OHSS with GnRH agonist trigger from 2011 to 2018, stratified into three groups based on treatment received: GnRH agonist trigger alone (Group 1, n = 208), GnRH agonist trigger + cabergoline (Group 2, n = 167) or GnRH agonist trigger + cabergoline + GnRH antagonist (Group 3, n = 105). Data on patient demographics, incidence, severity and symptomatology of OHSS and laboratory findings were collected. RESULTS: Group 1 had more free peritoneal fluid than Group 2 (28% versus 19%, P = 0.04) or Group 3 (28% versus 5%, P = 0.001). Group 1 reported abdominal discomfort and bloating more than Group 2 (33% versus 21%, P = 0.01) or Group 3 (33% versus 18%, P = 0.006). Group 1 had more electrolyte abnormalities than Group 2, who had more than Group 3. No patients developed severe OHSS. Mild and moderate OHSS rate was higher in Group 1 (38%) than Group 2 (29%, P = 0.048) or Group 3 (18%, P = 0.006) and in Group 2 than Group 3 (P = 0.046). CONCLUSION: Addition of cabergoline to GnRH agonist triggering in high-risk OHSS patients, and subsequent addition of GnRH antagonist for 5 days in the luteal phase, sequentially reduces the risk of mild and moderate OHSS and improves patient comfort compared with GnRH agonist trigger alone.

The Effect of Repeated Versus Initial Procalcitonin Measurements on Diagnosis of Infection in the Intensive Care Setting: A Prospective Observational Study.

Procalcitonin (PCT) measurement has been proposed to direct antibiotic use. We examined whether repeated PCT measurements (0, 6, and/or 12 hours) versus the initial measurement only (time 0) increased the sensitivity and specificity of PCT for diagnosing infection in intensive care unit patients. Infection was identified in 67/176 (38%) patients. The sensitivity of repeated versus the initial PCT measurement (with a cutoff value 0.5 ng/mL) was 52/67 (77%; 95% confidence interval [CI], 66%-87%) vs 46/67 (69%; 95% CI, 56%-79%; P = .04) and specificity 60/109 (55%; 95% CI, 45%-65%) vs 59/109 (54%; 95% CI, 44%-64%; P = 1.0). Repeat PCT evaluations over 12 hours did not provide a clinically significant improvement in diagnostic accuracy when compared to the initial single test.

When to do intracytoplasmic sperm injection: a prospective comparison.

PURPOSE: The purpose of the study was to assess the fertilization rate and embryo development in sibling human oocytes after split insemination in patients with and without isolated teratozoospermia. METHODS: A prospective cohort study at a university affiliated reproduction center was performed. Hundred and three patients during the time periods 01-2013 to 12-2015 had split insemination ordered for their first IVF cycle. The primary outcome measured was fertilization rate. Secondary outcomes were the number and quality of embryos. RESULTS: Mature oocytes at the time of collection were assigned as follows: 558 to IVF and 556 to ICSI. An additional 48 immature oocytes matured while awaiting spontaneous fertilization with IVF for a total of 606 in that group. The study group of normal strict sperm morphology ≤ 4 included 61 patients, and the control group included 42 patients with normal strict sperm morphology > 4. ICSI was statistically favored over IVF only in cases with normal strict sperm morphology ≤ 4%. There was a higher fertilization rate in ICSI compared to IVF (74.4% vs. 38%, p < 0.0001), a higher number of day 2 (4 ± 3.4 vs. 2.4 ± 2.7, p < 0.0001), day 3 (4 ± 3.4 vs. 2.2 ± 2.7, p < 0.0001) and day 5 embryos (2.2 ± 2.6 vs. 1.2 ± 2, p = 0.001), and they were of better quality; however, it did not reach significance (p = 0.062). A similar advantage for ICSI was seen in a subgroup of unexplained infertility with normal strict sperm morphology > 4%. CONCLUSIONS: In conclusion, in couples with normal strict sperm morphology ≤ 4%, there is an advantage of ICSI over IVF in terms of fertilization rate, quantity and quality of cleavage stage embryos and blastocysts. Based on the results, ICSI seems reasonable as a first-line treatment in patients with normal strict sperm morphology ≤ 4%, as well as in patients with unexplained infertility.

Poor ovarian response as a predictor for live birth in older women undergoing IVF.

Women of advanced age present a major challenge for fertility treatments. This study was designed to assess whether poor ovarian response (POR) according to the Bologna criteria is a significant predictor for live birth in women over 40. The outcomes of subsequent IVF cycles were also studied. The results of 1870 fresh IVF cycles in 1212 women were retrospectively analysed. The live birth per cycle was 3.3 times higher (11.61% versus 3.54%, P < 0.001) in good responders with more than three oocytes collected compared with women with less. Ovarian response defined by oocytes collected, but not by the number of follicles, was independently associated with live birth (odds ratio, 2.0; 95% confidence interval, 1.18 to 3.54; P = 0.009). The occurrence of POR in subsequent IVF cycles was only 55%. No differences in live births were found in persistent POR compared with women with at least one good response. A single episode of POR in a first IVF cycle in older women has a limited predictive value for the outcomes of subsequent cycles. POR in women aged 40-43 years, defined by the number of oocytes retrieved, is a predictor for live birth in IVF.

Combined modalities for the prevention of ovarian hyperstimulation syndrome following an excessive response to stimulation.

Although the classification and management of ovarian hyperstimulation syndrome (OHSS) are well described in the literature, little attention has been given to modalities that aim to prevent its occurrence. In this retrospective study, we sought to investigate whether a combination of modalities in addition to GnRH agonist triggering in GnRH antagonist cycles could result in better prevention of OHSS. The study included 170 hyperresponder patients who were stimulated with GnRH antagonist protocol and were triggered with GnRH agonist for final oocyte maturation. Freeze all embryos was performed in all patients. The intervention group included treatment with dopamine agonist and restarting the GnRH antagonist. Of the 170 patients included, 63 were included in the intervention group. Compared to no intervention, women in the intervention group were more likely to have: menses within 7 days of the oocyte retrieval, smaller ovarian diameter, the absence of free pelvic fluid, less hemoconcentration and higher serum sodium levels. It can be concluded that combining other modalities in addition to triggering with GnRH agonist in GnRH antagonist cycles, results in targeting several pathways that lead to OHSS and result in rapid resolution of signs of ovarian hyperstimulation.

Decreased pregnancy and live birth rates after vitrification of in vitro matured oocytes.

PURPOSE: To assess effects on fertilization rate, embryo quality, pregnancy, and live birth rates of vitrification and warming of oocytes that matured in vitro (vIVM) compared to fresh in vitro maturation (fIVM) cycles. METHODS: A retrospective cohort study conducted at a university hospital-affiliated IVF unit. Fifty-six cycles of vIVM cycles and 263 fIVM in women diagnosed with polycystic ovarian syndrome (PCOS) ovaries were included in the analysis. The study group included PCOS patients who failed ovulation induction with intrauterine insemination and were offered IVM cycle followed by oocyte vitrification and warming. The embryological aspects and clinical outcomes were compared to those of controls undergoing fresh IVM cycles during the same period. The main outcome measure was live birth rate. RESULTS: One thousand seventy oocytes were collected from 56 patients and underwent vitrification and warming. In the control group, 4781 oocytes were collected from 219 patients who had undergone a fresh IVM cycle. Oocyte maturation rates were similar between the groups (mean ± SD: 0.7 ± 0.2 vs. 0.6 ± 0.2, for vIVM and fIVM, respectively). Survival rate after warming was 59.8%. Fertilization and embryo cleavage rates per oocyte were significantly lower in the vIVM group. Clinical pregnancy (10.7 vs. 36.1%) and live birth rates (8.9 vs. 25.9%) per cycle were significantly lower in the vIVM group than those in the fIVM group (P = 0.005 and P < 0.001, respectively). Five healthy babies were born in the vIVM group. CONCLUSIONS: The reproductive potential of vitrified IVM oocytes is impaired. This injury likely occurs through vitrification and warming.

Prevalence, clinical characteristics, and reproductive outcomes of polycystic ovary syndrome in older women referred for tertiary fertility care.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age women. The clinical symptoms of PCOS vary with female age, as older women tend to have lower hyperandrogenic symptoms and many regain regular cycles. In this study, we aimed to estimate the prevalence of PCOS among older women referred for fertility care, describe their clinical characteristics, and compare their reproductive outcomes to those of matched control group. METHODS: A retrospective study conducted at a single reproductive center. All women aged ≥ 40, who were referred for in-vitro fertilization (IVF), between the years 2011-2015 were screened for possible inclusion. The PCOS diagnosis (was) made based on the Rotterdam criteria. The reproductive outcomes of the PCOS group were compared to those of matched control with tubal infertility. RESULTS: During the study period, 1427 women, aged 40 years and over, underwent a total of 2124 IVF cycles. Of these, 72 (5%) women were diagnosed with PCOS. In 69 (95.6%), the PCOS diagnosis was made by a combination of polycystic ovary morphology (PCOM) and anovulation. Compared to women with tubal factor infertility, women with PCOS needed lower doses of gonadotropins, had higher number of retrieved oocytes (16.6 vs. 10.4) and higher number of cycles with embryo cryopreservation (47 vs. 22.9%). This resulted in higher cumulative live birth in the PCOS group (26.3 vs. 15.2%, p = 0.04). CONCLUSION: PCOS comprised 5% of the infertility diagnosis in women aged ≥ 40; PCOM and anovulation were the most prominent features. The higher oocyte number resulted in improved cumulative live birth rate.

Predictive factors for live birth after in vitro maturation of oocytes in women with polycystic ovary syndrome.

OBJECTIVE: In vitro maturation (IVM) of human oocytes can be an alternative treatment option to conventional in vitro fertilization. Women with polycystic ovary syndrome (PCOS) are considered the classical candidates for IVM because of the associated ovarian morphology and because IVM diminishes the risk of developing ovarian hyperstimulation syndrome. The objective of this study was to identify predictive factors for live birth in a cohort of women with PCOS who underwent IVM. METHODS: This retrospective study included 159 patients with PCOS who had IVM cycles in which single or double embryo transfer was performed. The IVM protocol included three days of gonadotropin ovarian stimulation and hCG priming when the leading follicle size was 10-12 mm. Collected cumulus-oocyte complexes were cultured for 24 h for maturation. Intracytoplasmic sperm injection (ICSI) was used for fertilization. Embryo transfer was performed two days after fertilization. Demographic and clinical parameters were analyzed with logistic regression to identify predictors for live birth. RESULTS: The women's mean age was 27.4 years, the mean number of retrieved oocytes was 14, and the live birth rate was 34.6%. The logistic regression revealed the following significant factors for live birth: infertility duration (OR 0.9; 95% CI, 0.82-0.98), number of collected oocytes (OR 1.56; 95% CI, 1.01-3.2), embryo cell number (OR 2.1; 95% CI, 1.4-3.5), and embryo grade (OR 1.84; 95% CI, 1.13-4.2). CONCLUSION: Infertility duration, oocyte number, embryo cell number, and embryo grade were the most significant predictors for live birth after IVM in PCOS patients. These prognostic factors can be used when planning treatment or counselling patients.

The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age.

STUDY QUESTION: Does ICSI improve reproductive outcomes compared with conventional IVF when used for non-male factor infertility in women aged 40 years and over? SUMMARY ANSWER: There is no advantage of ICSI over conventional IVF in women aged 40 years and over when used for non-male factor infertility. WHAT IS KNOWN ALREADY: The use of ICSI has increased dramatically in recent years and is being applied for indications other than male factor infertility. Currently, ICSI is used in 65% of IVF cycles in Europe and in 76% of cycles in the USA. Despite its increase use, there is no clear evidence of a benefit in using ICSI over conventional IVF. Older women undergoing infertility treatments are at an increased risk of having diminished ovarian reserve and lower oocyte quality, which could make ICSI the preferred insemination method in this group. However, studies that have examined the benefits of ICSI in this age group are lacking. STUDY DESIGN, SIZE, DURATION: A retrospective, single center study included women, aged 40-43 years, who underwent IVF treatments for non-male factor infertility between January 2012 until June 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 745 women were included in the study. Of these, 490 women underwent ICSI and 255 women underwent conventional IVF. In order to be included in the study, women had to be at least 40 years of age at the beginning of ovarian stimulation and their male partner had to have normal sperm parameters according to World Health Organisation (WHO) fifth edition. Exclusion criteria included: more than three previous IVF cycles, a history of fertilization failure or low fertilization (<50%), the use of donor or frozen oocytes and the use of donor or frozen sperm samples. The primary outcome was the live birth rate. Secondary outcomes included fertilization rates, fertilization failure and embryo quality. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics were similar between the two groups, except for the number of previous IVF cycles, which was higher in the ICSI group (1.0 vs. 0.6, P = 0.0001). Despite similar numbers of oocytes retrieved (7.2 vs. 6.5), when examining oocytes maturity (performed 2 h after oocyte retrieval in the ICSI group and after 18 h in the conventional IVF group), the conventional IVF group had a higher number of Metaphase II (MII) oocytes (6.1 vs. 4.7, P < 0.0001). The conventional IVF group also had higher numbers of zygotes formed (4.48 vs. 3.66, P = 0.001), more cycles with embryos transferred at the blastocyst stage (36 vs. 26%, P = 0.005) and more cycles where embryos were available for cryopreservation (26.4 vs. 19.7%, P = 0.048), compared with the ICSI group. The fertilization rates (64 vs. 67%) and fertilization failure (9.0 vs. 9.7%) were similar. After logistic regression analysis controlling for confounders, the live birth rates were similar between the groups (11.9 vs. 9.6%). Subgroup analyses of women undergoing their first IVF cycle and women with ≤3 oocytes retrieved did not show an advantage of ICSI over conventional IVF. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of this study was a major limitation. The ICSI group had a higher number of previous IVF cycles, which could mean that ICSI was performed in poorer prognosis patients. Moreover, although this study is one of the largest studies to examine the question of whether ICSI is of value for older women with non-male factor infertility, based on a post hoc power analysis, it was still underpowered to detect differences in live birth rates, which can limit the conclusions of the study. Prospective studies are needed to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: The decision regarding performing ICSI should be based on sperm parameters and previous history. The use of ICSI for the sole indication of advanced maternal age shows no benefit over conventional IVF. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

Cumulative live birth rate following elective single blastocyst transfer compared with double blastocyst transfer in women aged 40 years and over.

This retrospective cohort study aimed to identify predictive factors for live birth following blastocyst transfer in women aged 40-43, and to compare the cumulative live birth rate (LBR) following elective single blastocyst (eSBT) and double blastocyst (DBT) transfer. The study included 411 women who had fresh blastocyst transfers on day 5. In stepwise logistic regression, independent predictive factors for live birth were: transferring fully expanded blastocysts (Gardner stage ≥3) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.59-9.71) and transferring two blastocysts compared with a single blastocyst (OR 1.7, 95% CI 1.08-2.9). Maternal age was not found to be significant (OR 0.78, 95% CI 0.62-1.1). When comparing eSBT (n = 150) with DBT (n = 151), the DBT group achieved higher LBRs (26.5 versus 19.3%, P = 0.017) and higher multiple births (0 versus 17.5%, P = 0.02). However, the cumulative LBR was similar (28.0 versus 31.1%), with significantly lower multiple births in the eSBT group (0 versus 14.9%, P = 0.03). These results indicate that in women aged 40-43, when fully expanded blastocysts are achieved, maternal age is not a predictor for live birth, and eSBT can be performed without compromising cumulative LBRs.

GnRH-agonist triggering for final oocyte maturation in GnRH-antagonist IVF cycles induces decreased LH pulse rate and amplitude in early luteal phase: a possible luteolysis mechanism.

The use of GnRH agonist to trigger final oocyte maturation in GnRH-antagonist in vitro fertilization (IVF) cycles has been shown to significantly reduce or even eliminate the risk of ovarian hyperstimulation syndrome (OHSS) by inducing rapid luteolysis early in the luteal phase. The exact mechanism of this early luteolysis is still widely unknown. Since luteinizing hormone (LH) has a major role in corpus luteum support, we sought to explore the pattern of LH secretion early in the luteal phase. Ten high risk patients for developing OHSS and triggered with GnRH agonist were included. Frequent blood sampling (every 20 min for 6 h) to measure LH, estradiol and progesterone was done on the day of oocyte collection (n = 5, Group 1) and on the day of embryo transfer, 48 h after oocyte collection (n = 5, Group 2). We found that the mean LH concentration and its secretion rate decreased significantly in Group 2 compared to Group 1. Both groups had similar number of LH pulses characterized by very small amplitude. In Group 2, there was a steady significant decrease in estradiol and progesterone over time. The results of this study show that LH secretion deviates significantly from normal physiologic pattern, which can explain, at least in part, the post-GnRH-agonist trigger early luteolysis mechanism.

Elective single blastocyst transfer in advanced maternal age.

PURPOSE: The purpose of this study was to investigate reproductive outcomes following elective single blastocyst transfer (eSBT) compared with those of double blastocyst transfer (DBT) in advanced maternal age. METHODS: This was a retrospective cohort study performed at an academic fertility center. All women aged 40 and over for whom in vitro fertilization (IVF) cycles were performed and in whom embryo culture was extended to the blastocyst stage were reviewed for possible inclusion. Exclusion criteria included the following: women with >3 previous IVF cycles, the use of donor or frozen oocytes, preimplantation genetic diagnosis/preimplantation genetic screening cycles, and cycles in which embryos did not reach the blastocyst stage on day 5. The study included 310 women; 148 were included in the eSBT group and 162 were included in the DBT group. Live birth rate (LBR) was the main outcome. Outcomes were analyzed using logistic regression, controlling for confounders. These confounders were embryo expansion, embryo quality, and the number of previous IVF cycles. RESULTS: The mean age of the whole group was 41 ± 0.91 years, and the LBR was 21.6%. The eSBT group and the DBT group achieved similar clinical pregnancy rates (33 vs. 33%) (OR 1.04; 95%CI, 0.62-1.75) and LBRs (20 vs. 22.8%) (OR 1.43; 95% CI, 0.78-2.64). The multiple birth rate was lower in the eSBT group (0 vs. 16%, p = 0.02). The subgroup of women who had elective DBT (eDBT) achieved a higher LBR (20 vs. 30.6%) (OR 2.32; 95% CI, 1.16-4.68) and a higher multiple birth rate (0 vs. 22%, p = 0.001). Cycles with early blastocyst transfers were associated with lower LBRs compared with cycles with fully expanded blastocyst transfers (11 vs. 24%, p = 0.02). CONCLUSION: The results of this study indicate that eSBT is associated with similar LBRs compared to the entire DBT cohort; however, when supernumerary blastocysts are available for cryopreservation, eDBT is associated with both higher LBRs and a higher number of multiple births. Studies assessing the cumulative LBR in advanced maternal age after single blastocyst transfer and subsequent frozen-thawed blastocyst transfers are needed.

Unexpected Significant Uterine Pathological Findings at Vaginal Hysterectomy Despite Unremarkable Preoperative Workup.

BACKGROUND: Several studies have addressed the issue of undetected uterine pathology in women undergoing hysterectomy for pelvic organ prolapse (POP). However, these studies differ largely with respect to the incidence of malignancy found, study population, and preoperative evaluation. OBJECTIVES: To assess the risk of unexpected pre-malignant and malignant uterine pathological findings after vaginal hysterectomy for POP repair, in a single medical center in Israel. METHODS: A retrospective study was performed of all patients who underwent vaginal hysterectomy due to symptomatic POP between January 1990 and April 2015 in a single tertiary medical center. Selected clinical and pathological data were retrieved from the computerized medical records. All specimens were routinely sent for histopathological assessment. All women were managed according to a uniform protocol that required the presence of a preoperative normal Pap smear, and included preoperative transvaginal sonography and endometrial biopsy when indicated. Patients in whom premalignant or malignant lesions were found preoperatively were not included in the study. RESULTS: The study comprised 667 patients. The overall rate of malignant or significant premalignant pathologies (6 cases) was 0.89%, including one (0.14%) case of endometrial carcinoma. All premalignant and malignant pathologies were found only in post-menopausal patients. The rate of significant endometrial pathological lesions found in asymptomatic post-menopausal women was only 0.35%. CONCLUSIONS: The rate of preoperatively undetected abnormal histopathological findings in patients who undergo vaginal hysterectomy due to POP is very low, and therefore more extensive preoperative evaluation is not warranted in them.

[Assisted reproductive technology in the presence of chronic viral disease].

INTRODUCTION: The first fertility unit dedicated to the treatment of couples infected with chronic viral diseases in Israel was established at the Rambam Medical Center in 2010. A multidisciplinary approach is needed in order to provide appropriate treatment to the viral disease, and to minimize the risks of infecting the partner, the embryo and others in the fertility unit. OBJECTIVE: To review 2 years-experience providing fertility care to couples seropositive for HIV, HBV and HCV. METHODS: Retrospective study. RESULTS: Between the years 2010-2012, 92 couples underwent 183 oocyte retrievals and fresh embryo transfers and 77 cycles of frozen-thawed embryo transfer. Forty three percent of the couples were seropositive to HBV, 30% seropositive to HIV, 20% seropositive to HCV and 7% infected with more than one virus. In 52.3% of cases the male partner was infected, in 38% the female partner was infected and in 9.7% both partners were infected. Fifty one percent of the couples received antiviral therapy before admission to the unit or did not need antiviral therapy due to inactive disease. Twenty nine percent of the couples received anti-viral drugs while being treated in the fertility unit and 10% needed anti-viral treatment before beginning fertility treatment due to high viral load. Horizontal or vertical viral disease transmissions were not recorded. CONCLUSION: Upon admission to the fertility unit the majority of couples had good control of their viral infections and either was under anti-viral treatment or did not need any further treatment. From our experience and a review of the literature, controlling the viral disease is the key to safe fertility treatment, and eliminating the risk of infecting the embryo, newborn, partner, and others within the fertility unit.