Prevalence of T-shaped uterus among fertile women based on ESHRE/ESGE and Congenital Uterine Malformation by Experts (CUME) criteria.

RESEARCH QUESTION: What is the prevalence of T-shaped uteri among fertile women based on ESHRE/ESGE and Congenital Uterine Malformation by Experts (CUME) criteria? DESIGN: A prospective cohort study of 258 women of reproductive age with a history of at least one natural pregnancy resulting in live birth. Participants were recruited from the family planning clinic between January 2018 and March 2020. The ESHRE/ESGE classification of congenital anomalies of the female genital tract was used for describing abnormal findings. CUME criteria were also used for diagnosing T-shaped uterus. Uterine cavity volume was measured. RESULTS: Mean age of participants was 35.4 ± 6.2 years. Participants were diagnosed with the following: congenital uterine abnormality (n = 9 [3.6%]); partial septate uterus (n = 5 [2.0%]) and hemiuterus (n = 2 [0.8%]). Two women (0.8%) were diagnosed with T-shaped uterus and borderline T-shaped uterus based on the ESHRE/ESGE criteria and CUME. Mean lateral indentation angle, lateral indentation depth and T-angle were 156.2° ± 9.53°, 2.85 ± 0.93 mm and 73.3° ± 9.85° in patients with normal uterine cavity. In patients with T-shaped and borderline T-shaped uteri, respective figures were 115° versus 121°, 10 mm versus 7.6 mm and 27.5° versus 70°. Median volume of the uterine cavity in patients with normal uterine cavity and T-shaped uterus was 3.71 ml (minimum 2.0 to maximum 9.03 ml, interquartile range 1.93) and 3.2 ml (2.9 and 3.62 ml), respectively. CONCLUSIONS: The prevalence of T-shaped uteri in fertile women is low, which corresponds to previous reports of women with poor reproductive history.

Luteal granulosa cells from natural cycles are more capable of maintaining their viability, steroidogenic activity and LH receptor expression than those of stimulated IVF cycles.

STUDY QUESTION: Are there any differences in the molecular characteristics of the luteal granulosa cells (GC) obtained from stimulated versus non-stimulated (natural) IVF cycles that may help explain the defective luteal phase in the former? SUMMARY ANSWER: Luteal GC of stimulated IVF cycles, particularly those of agonist-triggered antagonist cycles, are less viable ex vivo, express LH receptor and anti-apoptotic genes at lower levels, undergo apoptosis earlier and fail to maintain their estradiol (E2) and progesterone (P4) production in comparison to natural cycle GC. WHAT IS KNOWN ALREADY: Luteal function is defective in stimulated IVF cycles, which necessitates P4 and/or hCG administration (known as luteal phase support) in order to improve clinical pregnancy rates and prevent miscarriage. The luteal phase becomes shorter and menstruation begins earlier than a natural cycle if a pregnancy cannot be achieved, indicative of early demise of corpus luteum (premature luteolysis). Supra-physiological levels of steroids produced by multiple corpora luteae in the stimulated IVF cycles are believed to inhibit LH release directly via negative feedback actions on the hypothalamic-pituitary-ovarian axis resulting in low circulating levels of LH and a defective luteal phase. We hypothesized that some defects in the viability and steroidogenic activity of the luteal GC of the stimulated IVF cycles might contribute to this defective luteal phase in comparison to natural cycle GC. This issue has not been studied in human before. STUDY DESIGN, SIZE, DURATION: A comparative translational research study of ex vivo and in vitro models of luteal GC recovered from IVF patients undergoing natural versus stimulated IVF cycles was carried out. Luteinized GC were obtained from 154 IVF patients undergoing either natural (n = 22) or stimulated IVF cycles with recombinant FSH and GnRH agonist (long) (n = 44), or antagonist protocol triggered conventionally either with recombinant hCG (n = 46) or with a GnRH agonist (n = 42). GC were maintained in vitro for up to 6 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cellular viability (YO-PRO-1 staining), the expression of the steroidogenic enzymes, pro-apoptotic genes [Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX) and Caspase-3 (CASP3)], anti-apoptotic genes [RAC-alpha serine/threonine-protein kinase (AKT-1) and Bcl-2-like protein 2 (BCL2-L2)], LH receptor, vascular endothelial growth factor (VEGF) (using real-time quantitative PCR at mRNA level and western blot immunoprecipitation assay at protein level) and in vitro E2 and P4 production (electrochemiluminescence immunoassay) were compared in GC among the groups. MAIN RESULTS AND THE ROLE OF CHANCE: Natural cycle GC were significantly more viable ex vivo (88%) compared to their counterparts of the stimulated IVF cycles (66, 64 and 37% for agonist and antagonist cycles triggered with hCG and GnRH agonist respectively, P < 0.01). They were also more capable of maintaining their vitality in culture compared to their counterparts from the stimulated IVF cycles: at the end of the 6-day culture period, 74% of the cells were still viable whereas only 48, 43 and 22% of the cells from the agonist and antagonist cycles triggered with hCG and agonist respectively, were viable (P < 0.01). The mRNA expression of anti-apoptotic genes (AKT-1 and BCL2-L2) was significantly lower, while that of pro-apoptotic genes (BAD, BAX and CASP3) was significantly higher in the stimulated cycles, particularly in the agonist-triggered antagonist cycles, compared to natural cycle GC (P < 0.01 for long protocol and antagonist hCG trigger, P < 0.001 for agonist trigger). The expression of steroidogenic enzymes (stAR, SCC, 3ß-HSD and aromatase) and VEGF was significantly higher in the agonist and hCG-triggered antagonist cycles compared to natural cycle GC. Therefore, in vitro E2 and P4 production in cells from the stimulated IVF cycles was significantly higher than their counterparts obtained from the natural cycles in the first 2 days of culture. However, after Day 2, their viability and hormone production began to decline very rapidly with the most drastic decrease being observed in the agonist-triggered cycles. By contrast, natural cycle GC maintained their viability and produced E2 and P4 in increasing amounts in culture up to 6 days. In vitro P production and the mRNA and protein expression of LH receptor, VEGF and 3ß-HSD were most defective in the agonist-triggered antagonist cycles compared to natural and agonist and hCG-triggered antagonist cycles. In vitro hCG treatment of a subset of the cells from the agonist-triggered cycles improved their viability, increased E2 and P4 production in vitro and up-regulated the mRNA expression of anti-apoptotic gene BCL-L2 together with steroidogenic enzymes stAR, SCC, 3B-HSD, LH receptor and VEGF. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: The limitations include analysis of luteinized GC only might not reflect the in vivo mechanisms involved in survival and function of the whole corpus luteum; GC recovered during oocyte retrieval belong to a very early stage of the luteal phase and might not be representative; effects of ovulation triggered with hCG may not equate to the endogenous LH trigger; the clinical characteristics of the patients may vary among the different groups and it was not possible to correlate stimulation-related molecular alterations in luteal GC with the clinical outcome, as no oocytes have been utilized yet. Therefore, our findings do not conclusively rule out the possibility that some other mechanisms in vivo may also account for defective luteal function observed in stimulated IVF cycles. WIDER IMPLICATIONS OF THE FINDINGS: Ovarian stimulation is associated with significant alterations in the viability and steroidogenic activity of luteal GC depending on the stimulation protocol and mode of ovulation trigger. Reduced survival and down-regulated expression of 3B-HSD, LH receptor and VEGF leading to compromised steroid production in stimulated cycles, and particularly in the agonist-triggered cycles, may at least in part help explain why the luteal phase is defective and requires exogenous support in these cycles. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest.

Diminished ovarian reserve versus ovarian aging: overlaps and differences.

PURPOSE OF REVIEW: Diminished ovarian reserve, in general, implies a quantitative decline in the oocyte pool. However, whether this quantitative decline is necessarily accompanied by a qualitative decline, remains to be determined. RECENT FINDINGS: Studies of natural conception suggest that fecundity of women with a quantitative decline in ovarian reserve is similar to age-matched women with normal ovarian reserve. Data on rates of pregnancy loss and fetal chromosomal abnormality do not consistently suggest a decline in oocyte quality in women who has a lower ovarian reserve. In assisted reproductive technology (ART) cycles, oocytes from women with diminished ovarian reserve have similar potential for euploid blastocyst development. Likewise, available evidence does not strongly suggest an increased risk of pregnancy loss in women with diminished reserve undergoing ART treatment as compared with similarly aged woman with normal ovarian reserve. SUMMARY: Quantitative decline in ovarian reserve may not be necessarily accompanied by a qualitative decline. Although a decreased number of follicles and poor response to ovarian stimulation are hallmarks of ovarian aging, younger women with diminished ovarian reserve may not be experiencing the distinct effects of aging on oocyte quality.

Do endometriomas grow during ovarian stimulation for assisted reproduction? A three-dimensional volume analysis before and after ovarian stimulation.

Whether endometriomas grow because of supraphysiological oestradiol levels attained during ovarian stimulation for assisted reproduction techniques is a concern. In this prospective study, 25 women with 28 endometriomas underwent three-dimensional ultrasound using sono-automated volume calculation software. Endometrioma volume was measured on the first day of gonadotrophin injection (V1) and the day of ovulation trigger (V2). Nine (36%) women were stimulated in a gonadotrophin releasing hormone antagonist protocol (GnRH), 13 (52%) in a long, and three (12%) in an ultra-long GnRH agonist protocol. Mean duration of stimulation was 10.3 days with median total gonadotrophin dose of 4500 IU/day. Median number of cumulus oocyte complexes was five, and metaphase-two oocytes was four. None of the endometriomas were punctured during oocyte retrieval. Median V1 was 22.2 ml (12-30 ml) and median V2 was 24.99 ml (11.2-37.4 ml) with P = 0.001. Twenty-three out of 28 endometriomas (82%) grew to some extent during ovarian stimulation. Endometrioma growth was positively correlated with prestimulation cyst volume (Correlation coefficient 0.664; P < 0.01). Although the 3-ml average growth was statistically significant, it could be regarded as clinically insignificant.

Application of seminal plasma to female genital tract prior to embryo transfer in assisted reproductive technology cycles (IVF, ICSI and frozen embryo transfer).

BACKGROUND: The female genital tract is not exposed to seminal plasma during standard assisted reproductive technology (ART) cycles. However, it is thought that the inflammatory reaction triggered by seminal plasma may be beneficial by inducing maternal tolerance to paternal antigens expressed by the products of conception, and may increase the chance of successful implantation and live birth. OBJECTIVES: To assess the effectiveness and safety of application of seminal plasma to the female genital tract prior to embryo transfer in ART cycles. SEARCH METHODS: We searched the following databases from inception to October 2017: Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, Cochrane Central Register of Studies Online (CRSO), MEDLINE, Embase, CINAHL and PsycINFO. We also searched trial registers for ongoing trials, including International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Other sources searched were; Web of Knowledge, OpenGrey, LILACS, PubMed, Google Scholar and the reference lists of relevant articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) conducted among women undergoing ART, comparing any procedure that would expose the female genital tract to seminal plasma during the period starting five days before embryo transfer and ending two days after it versus no seminal plasma application. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias, and extracted data. We pooled data to calculate relative risks (RRs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I2 statistic. We assessed the overall quality of the evidence for the main outcomes using GRADE methods. Our primary outcomes were live birth rate and miscarriage rate. Secondary outcomes were live birth/ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate and the incidence of other adverse events. MAIN RESULTS: We included 11 RCTs (3215 women). The quality of the evidence ranged from very low to low. The main limitations were risk of bias (associated with poor reporting of allocation concealment and other methods) and imprecision for the primary outcome of live birth rate.Live birth rates: There was insufficient evidence to determine whether there was a difference between the groups with respect to live birth rates (RR 1.10, 95% CI 0.86 to 1.43; participants = 948; studies = 3; I2 = 0%). Low quality evidence suggests that if the live birth rate following standard ART is 19% it will be between 16% and 27% with seminal plasma application.Miscarriage rate: There was insufficient evidence to determine whether there was a difference between the groups (RR 1.01, 95% CI 0.57 to 1.79; participants = 1209; studies = 4; I2 = 0%). Low quality evidence suggests that if the miscarriage rate following standard ART is 3.7%, the miscarriage rate following seminal plasma application will be between 2.1% and 6.6%.Live birth or ongoing pregnancy rates: Seminal plasma application makes little or no difference in live birth or ongoing pregnancy rates (RR 1.19, 95% CI 0.95 to 1.49; participants = 1178; studies = 4; I2 = 4%, low quality evidence). The evidence suggests that if the live birth or ongoing pregnancy rate following standard ART is 19.5% it will be between 18.5% and 29% with seminal plasma application.Clinical pregnancy rates: Seminal plasma application may increase clinical pregnancy rates (RR 1.15, 95% CI 1.01 to 1.31; participants = 2768; studies = 10; I2 = 0%). Very low quality evidence suggests that if the clinical pregnancy rate following standard ART is 22.0% it will be between 22.2% and 28.8% with seminal plasma application. This finding should be regarded with caution, as a post-hoc sensitivity analysis restricted to studies at overall low risk of bias did not find a significant difference between the groups (RR 1.06, 95% CI 0.81 to 1.39; participants = 547; studies = 3; I2 = 0%).Multiple pregnancy rate: Seminal plasma application may make little or no difference to multiple pregnancy rates (RR 1.11, 95% CI 0.76 to 1.64; participants = 1642; studies = 5; I2 = 9%). Low quality evidence suggests that if the multiple pregnancy rate following standard ART is 7%, the multiple pregnancy rate following seminal plasma application will be between 5% and 11.4%.Ectopic pregnancy: There was insufficient evidence to determine whether seminal plasma application influences the risk of ectopic pregnancy (RR 1.59, 95% CI 0.20 to 12.78, participants =1521; studies = 5; I2 = 0%) .Infectious complications or other adverse events: No data were available on these outcomes AUTHORS' CONCLUSIONS: In women undergoing ART, there was insufficient evidence to determine whether there was a difference between the seminal plasma and the standard ART group in rates of live birth (low-quality evidence) or miscarriage (low quality evidence). There was low quality evidence suggesting little or no difference between the groups in rates of live birth or ongoing pregnancy (composite outcome). We found low quality evidence that seminal plasma application may be associated with more clinical pregnancies than standard ART. There was low quality evidence suggesting little or no difference between the groups in rates of multiple pregnancy. There was insufficient evidence to reach any conclusions about the risk of ectopic pregnancy, and no data were available on infectious complications or other adverse events.We conclude that seminal plasma application is worth further investigation, focusing on live birth and miscarriage rates.

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.

Which is worse? Comparison of ART outcome between women with primary or recurrent endometriomas.

STUDY QUESTION: Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma? SUMMARY ANSWER: Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma. WHAT IS ALREADY KNOWN: Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas. STUDY DESIGN, SIZE, DURATION: A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3). LIMITATIONS, REASONS FOR CAUTION: The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment. WIDER IMPLICATIONS OF THE FINDINGS: The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests to declare. TRIAL REGISTRATION NUMBER: None.

Effect of hemostatic method on ovarian reserve following laparoscopic endometrioma excision; comparison of suture, hemostatic sealant, and bipolar dessication. A systematic review and meta-analysis.

We reviewed the literature to determine whether different hemostatic methods used following laparoscopic endometrioma excision have differing effects on ovarian reserve. We performed a systematic literature search using the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Ovid MEDLINE In-Process & Other Non-Indexed Citations databases to identify studies comparing the rate of change in levels of serum anti-Müllerian hormone (AMH) at 3 months after laparoscopic endometrioma excision using bipolar dessication (BD) or suturing/application of a hemostatic sealant (HS) for hemostasis. Abstracts of the annual meetings of the American Society of Reproductive Medicine, the European Society of Human Reproduction and Embryology, and the American Association of Gynecological Laparoscopists were searched as well. A total of 712 articles were identified, of which 6 were included in the qualitative analysis. Four studies involving 213 women were included in the meta-analysis. Our qualitative analysis suggested that BD is more detrimental to ovarian reserve than alternative hemostatic methods. There is moderate-quality evidence favoring HS and low-quality evidence favoring sutures over BD. The meta-analysis also showed that alternative hemostatic methods are associated with significantly less decline in ovarian reserve compared with BD. The mean decline in serum AMH levels was 6.95% less with alternative hemostatic methods than with BD (95% CI, -13.0% to -0.9%; p = .02) at 3 months after surgery. According to the best available evidence, the use of BD should be cautiously limited, even avoided when possible, during endometrioma excision in women who desire to have children.

Impact of Temperature Optimization of ITO Thin Film on Tandem Solar Cell Efficiency.

This study examined the impact of temperature optimization on indium tin oxide (ITO) films in monolithic HJT/perovskite tandem solar cells. ITO films were deposited using magnetron sputtering at temperatures ranging from room temperature (25 °C) to 250 °C. The sputtering target was ITO, with a mass ratio of In2O3 to SnO2 of 90% to 10%. The effects of temperature on the ITO film were analyzed using X-ray diffraction (XRD), spectroscopic ellipsometry, and sheet resistance measurements. Results showed that all ITO films exhibited a polycrystalline morphology, with diffraction peaks corresponding to planes (211), (222), (400), (440), and (622), indicating a cubic bixbyite crystal structure. The light transmittance exceeded 80%, and the sheet resistance was 75.1 Ω/sq for ITO deposited at 200 °C. The optical bandgap of deposited ITO films ranged between 3.90 eV and 3.93 eV. Structural and morphological characterization of the perovskite solar cell was performed using XRD and FE-SEM. Tandem solar cell performance was evaluated by analyzing current density-voltage characteristics under simulated sunlight. By optimizing the ITO deposition temperature, the tandem cell achieved a power conversion efficiency (PCE) of 16.74%, resulting in enhanced tandem cell efficiency.

Prospective assessment of the impact of endometriomas and their removal on ovarian reserve and determinants of the rate of decline in ovarian reserve.

STUDY QUESTION: Do the presence of endometriomas and their laparoscopic excision lead to a decrease in ovarian reserve as assessed by serum anti-Müllerian hormone (AMH) levels? SUMMARY ANSWER: Both the presence and excision of endometriomas cause a significant decrease in serum AMH levels, which is sustained 6 months after surgery. WHAT IS KNOWN ALREADY: No previous comparison of serum AMH levels between women with and without endometrioma has been reported. However, studies have suggested a decline in serum AMH levels 1-3 months after endometrioma excision but long-term data are needed. STUDY DESIGN, SIZE, DURATION: A prospective cohort study including 30 women with endometrioma >2 cm were age matched with 30 healthy women without ovarian cysts. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with endometrioma underwent laparoscopic excision with the stripping technique. Serum AMH level and antral follicle count (AFC) were determined preoperatively, 1 and 6 months after surgery. Correlation analyses were undertaken in order to identify determinants of surgery-related change in ovarian reserve. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with controls at baseline, women with endometrioma had lower AMH levels (4.2 ± 2.3 versus 2.8 ± 2.2 ng/ml, respectively, P = 0.02) and AFC (14.7 ± 4.1 versus 9.7 ± 4.8, respectively, P < 0.01). Serum AMH levels were further decreased 6 months after surgery (2.8 ± 2.2 versus 1.8 ± 1.3 ng/ml, P = 0.02), while AFC remained unchanged (9.7 ± 4.8 versus 10.4 ± 4.2, P = 0.63). The rate of decline in AMH was not correlated with age, laterality of endometrioma, cyst diameter or the number of primordial follicles on the surgical specimens. The preoperative serum AMH level was positively correlated with the rate of decline in serum AMH after surgery (r = 0.47, P = 0.02). LIMITATIONS, REASONS FOR CAUTION: The absence of a non-treated group of women with endometriomas as a further control prevents comment on the presence of a progressive decline in ovarian reserve related to endometrioma per se. The sample size may be too small for detection of factors correlated with the extent of ovarian damage. WIDER IMPLICATIONS OF THE FINDINGS: While the findings are mostly in agreement with previous studies, the present study is the first to show that the presence of endometrioma per se is associated with a decrease in ovarian reserve. The extent of surgery-related decline in ovarian reserve is not predictable using preoperative or perioperative factors. It may be prudent to measure AMH levels preoperatively and delay/avoid surgical excision as far as is possible if subsequent fertility is a concern. Additional studies are required to further investigate whether the endometrioma-related decline in ovarian reserve per se is progressive in nature and whether it exceeds the surgery-related decline. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Research Fund of the Uludag University School of Medicine. The authors have no conflict of interest associated with this study.

Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG.

STUDY QUESTION: Is severe early ovarian hyperstimulation syndrome (OHSS) completely prevented with the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol? SUMMARY ANSWER: Severe early OHSS can occur even after the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol. WHAT IS KNOWN ALREADY: Prior studies including over 200 women who received the GnRH agonist trigger and 1500 hCG luteal rescue protocol have reported complete prevention of severe early OHSS. Only a few late OHSS cases have been reported and it has been suggested that this protocol can be safely applied to any women under risk. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included all women who were at high risk of OHSS and were given the GnRH agonist trigger plus hCG luteal rescue protocol between December 2008 and August 2012 in the two participating centers. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 23 women with a mean estradiol level of 4891 ± 2214 pg/ml and a mean number of >12 mm follicles of 20 ± 6 on the day of ovulation triggering. OHSS was categorized according to the Golan criteria. MAIN RESULTS AND THE ROLE OF CHANCE: Overall 6 of the 23 (26%) women developed severe OHSS. Five women had severe early OHSS requiring ascites drainage and hospitalization and three of these women did not undergo embryo transfer. The number of follicles measuring 10-14 mm on the day of triggering was significantly different between women who developed severe early OHSS and those who did not. LIMITATIONS, REASONS FOR CAUTION: The small number of women with severe early OHSS may have prevented identification of other significant risk factors. WIDER IMPLICATIONS OF THE FINDINGS: Although the GnRH agonist plus 1500 IU hCG luteal rescue protocol significantly decreases the risk of severe OHSS, this life threatening complication can still occur in high-risk patients. It would be prudent to avoid hCG luteal rescue and freeze all embryos for future transfer in such women particularly when there are ≥18 follicles with 10-14 mm diameters even with few larger follicles.

Comparison of automated and manual follicle monitoring in an unrestricted population of 100 women undergoing controlled ovarian stimulation for IVF.

BACKGROUND: Ovarian response to gonadotrophin stimulation is monitored with serial ultrasound (US) examinations. Sonography-based Automated Volume Count (SonoAVC) is a relatively new three-dimensional (3D) US technology, which automatically generates a set of measurements including the mean follicular diameter (MFD) and a volume-based diameter (d(V)) for each follicle in the ovaries. The present study aimed to assess the applicability and reproducibility of this automated follicle measurement method in an IVF programme. METHODS: For this prospective method comparison study, 100 women undergoing US monitoring of a controlled ovarian stimulation cycle were recruited. Each follicle was manually measured by taking the mean of maximal diameters on three orthogonal planes with two-dimensional (2D) US. A 3D volume of each ovary was then captured. The ovarian volumes were later analysed using SonoAVC. The agreement between the two methods for the numbers of follicles and the size of the leading follicle was assessed with the Bland-Altman method. The reproducibility of SonoAVC measurements was assessed with the intraclass correlation coefficient (ICC). RESULTS: Both SonoAVC-generated MFD and d(V)-based follicle counts, as well as the leading follicle diameter, had good agreement with conventional 2D US measurements. SonoAVC measurements had very good reproducibility, with ICC ≥0.8 for most evaluations. CONCLUSIONS: Automated follicle monitoring with SonoAVC can replace or be used interchangeably with conventional 2D measurements. Automated follicle monitoring can save time, provide a method of quality control and create opportunities for developing HCG criteria based on follicular volume or for monitoring patients from a distance.

A Survey of Women Who Cryopreserved Oocytes for Non-medical Indications (Social Fertility Preservation).

To evaluate the expectations, experiences, and fertility awareness status of women who underwent social oocyte cryopreservation. Cohort survey study was conducted at an academic medical center. All women who underwent social oocyte cryopreservation between January 2015 and June 2016 were recruited. One hundred thirty-three women were contacted by phone to participate in a survey. The questionnaire investigated the initial motivation towards freezing, intentions to use cryopreserved oocytes, treatment experience, awareness of fertility and knowledge about chances of having a live birth with their frozen oocytes. The mean age at the time of oocyte freezing was 38.5 ± 2.68 years. The average number of mature oocytes cryopreserved was 5.48 ± 6.6 (1-16). Two major motivations were absence of a male partner (40%) and an anticipated age-related fertility decline (42%). Almost 60% overestimated the chances of natural conception, as well as the success of IVF at the age of 40 years. Half of the oocyte bankers reported that fertility declined between ages 35 and 39, but only 28% of patients estimated the live birth rate per cryopreserved oocyte correctly. Overall 98.8% stated that they would recommend oocyte cryopresevation to a friend, and 72% felt more secure in terms of reproductive potential. Despite comprehensive personalized counseling prior to the start of ovarian stimulation, many women do not seem to have a realistic understanding of reproductive aging. Even though gamete cryopreservation provides some insurance, overestimating the effectiveness of oocyte cryopreservation can also lead to a false sense of security. Clinical Trial Registration: 2016.086.IRB1.006.

Effect of high-dose estrogen in luteal phase support on live birth rates after assisted reproduction treatment cycles.

OBJECTIVE: The role of estrogen administration for luteal phase support (LPS) after assisted reproductive technologies treatment is not well established. While most studies report ineffectiveness of doses up to 4 mg/day, a small randomized, controlled trial suggested improved clinical outcome with higher dosage of 6 mg/day. The present pilot trial assessed effectiveness of 6 mg/day estrogen in addition to progesterone administration for LPS. STUDY DESIGN: Randomized, controlled trial. Sixty women undergoing assisted reproduction treatment were randomly allocated to receive progesterone vaginal gel with or without 6 mg/day 17beta-estradiol (E2) orally starting from the embryo transfer day. RESULTS: Embryo implantation rates were 33.33% and 28.9% in the control and E2 groups, respectively (p = 0.64). There were 11 (36.7%) live births in the control group, while there were 10 (33.3%) live births in the E2 group (p = 0.79). CONCLUSION: Our results do not suggest a beneficial effect of orally administered estrogen as adjuncts to progesterone for luteal support when administered to all patients in an unselective manner, even in a dose of 6 mg/day.

Medical treatment of uterocutaneous fistula with gonadotropin-releasing hormone agonist administration.

BACKGROUND: Uterocutaneous fistula is a rare complication of uterine surgery. All published cases have been surgically treated with hysterectomy and excision of the fistulous tract. We report a case of uterocutaneous fistula that was successfully treated with gonadotropin-releasing hormone agonist administration. CASE: A 25-year-old woman reported bloody discharge during her periods from a previous Pfannenstiel incision. A fistulous tract leading from the incision scar to the uterus was diagnosed. Leuprolide acetate depot was administered twice subcutaneously at a dose of 11.25 mg. The fistulous tract closed spontaneously, and the patient was symptom free thereafter. CONCLUSION: Medical treatment with gonadotropin-releasing hormone agonists should be considered before resorting to surgery for treatment of uterocutaneous fistulae.

Endometrioma-related reduction in ovarian reserve (ERROR): a prospective longitudinal study.

OBJECTIVE: To evaluate whether endometrioma is associated with a progressive decline in ovarian reserve, and to compare the rate of decline with natural decline in ovarian reserve. DESIGN: Prospective, observational study. SETTING: Tertiary university hospital, endometriosis clinic. PATIENT(S): Forty women with endometrioma and 40 age-matched healthy controls. INTERVENTION(S): Women with endometriomas who did not need hormonal/surgical treatment at the time of recruitment and were expectantly managed. Controls were age-matched, healthy women. All participants underwent serum antimüllerian hormone (AMH) testing twice, 6 months apart. Sexually active patients with endometrioma also underwent antral follicle count. MAIN OUTCOME MEASURE(S): Change in serum AMH levels. RESULT(S): Median (25th-75th percentile) serum AMH level at recruitment was 2.83 (0.70-4.96) ng/mL in the endometrioma group and 4.42 (2.26-5.57) ng/mL in the control group. The median percent decline in serum AMH level was 26.4% (11.36%-55.41%) in the endometrioma group and 7.4% (-11.98%, 29.33%) in the control groups. Twenty-two women with endometrioma who had antral follicle count (AFC) had median AFC of 10 (8-12) at recruitment and 8 (6.3-10) at 6 months. CONCLUSION(S): Women with endometrioma experience a progressive decline in serum AMH levels, which is faster than that in healthy women. CLINICAL TRIAL REGISTRATION NUMBER: NCT02438735.

Short and long term outcomes of children conceived with assisted reproductive technology.

Despite their wide and global use, possible short and long-term effects of fertility treatments on children is not well-established. In this review, birth defects and perinatal complications and their relationship with assisted reproductive technology (ART), along with long-term effects of ART on cardiovascular system, metabolism, behavior, cognitive skills, and childhood cancers are discussed. Children conceived through ART are at increased risk for birth defects and perinatal complications such as preterm delivery, low birth weight and small for gestational age. Parental characteristics, underlying infertility etiology and ART procedures themselves may contribute to this. The long-term effects of ART are difficult to establish. Studies so far report that ART children have normal social, emotional, cognitive, and motor functions. Likewise, despite some minor inconsistencies in some studies, they do not seem to be at increased risk for childhood cancers. However, there are a number of studies that imply vascular system may be adversely affected by ART and its possible consequences should be further investigated with follow up studies. Large scale studies with long-term follow up periods are required to determine the effects of ART on conceived children.