Endocrine-disrupting chemical concentrations in follicular fluid and follicular reproductive hormone levels.

PURPOSE: To determine correlations between chemicals in follicular fluid (FF) and follicular reproductive hormone levels. METHODS: The analysis was part of a larger cohort study to determine associations between exposure to EDCs and in vitro fertilization (IVF) outcomes. FF was aspirated from a single leading follicle per participant. Demographics and data on exposure to EDCs were self-reported by the participants using a questionnaire. The concentrations of estradiol (E2), progesterone (PG), anti-Mullerian hormone (AMH), and inhibin B, as well as that of 12 phthalate metabolites and 12 phenolic chemicals were measured in each FF sample. Multivariate linear regression model was used to identify the drivers of hormone levels based on participant's age, BMI, smoking status, and chemical exposure for the monitored chemicals detected in more than 50% of the samples. Benjamini-Hochberg false discovery rate (FDR) correction was applied on the resulting p values (q value). RESULTS: FF samples were obtained from 72 women (mean age 30.9 years). Most of the phthalates and phenolic substances monitored (21/24, 88%) were identified in FF. Ten compounds (7 phthalate metabolites, 3 phenols) were found in more than 50% of samples. In addition, there were positive associations between E2 levels and mono-n-butyl phthalate (MnBP) (beta = 0.01) and mono-isobutyl phthalate (MiBP) (beta = 0.03) levels (q value < 0.05). CONCLUSION: Higher concentrations of several phthalate metabolites, present among others in personal care products, were associated with increased E2 levels in FF. The results emphasize the need to further investigate the mechanisms of action of such EDCs on hormonal cyclicity and fertility in women.

Clinical features of isolated Fallopian tube torsion: evidence from a large series.

We aimed at studying isolated Fallopian tube torsion (IFTT) in a relatively large cohort of women and to evaluate different features of IFTT in comparison to a large cohort of women with non-IFTT adnexal torsion (NIAT). This was a retrospective cohort study. We included women with surgically confirmed ovarian and/or Fallopian tube torsion between March 2011 and June 2020. Fifty-four cases of IFTT were surgically confirmed during the study period and were compared to 422 surgically confirmed NIAT. The rate of controlled ovarian hyperstimulation treatments, current pregnancy, and vomiting was lower in the IFTT group compared with the NIAT group. Cervical tenderness and vaginal discharge were more common in the IFTT group. Oedematous and enlarged ovaries were less common in the IFTT group. In multivariate regression analysis, the following factors were independently associated with IFTT: (i) vaginal discharge [adjusted odds ratio (aOR) 95% CI 8.16, 1.98-33.55]; (ii) cervical motion tenderness (aOR 95% CI 2.71, 1.01-7.29); (iii) fertility treatments (aOR 95% CI 0.26, 0.70-0.77); (iv) previous abdominal surgery (aOR 95% CI 0.46, 0.22-0.96); (v) vomiting (aOR 95% CI 0.38, 0.19-0.76); and (vi) enlarged ovary (aOR 95% CI 0.34, 0.18-0.65). In conclusion, we have identified factors positively and negatively associated with IFTT in a large cohort of women with adnexal torsion.

MRI guided focused ultrasound (MRgFUS) treatment for uterine fibroids among women with and without abdominal scars.

INTRODUCTION: MRI guided focused ultrasound (MRgFUS) is a noninvasive technique for treating uterine fibroids. The presence of abdominal scars can limit the number of women eligible for the procedure, due to absorbance of beam energy. The goals of this study were to assess the number of women that fit the procedure and to compare outcomes among women with or without abdominal scars. MATERIAL AND METHODS: A prospective cohort study of all women that were interested in MRgFUS in a single University-Affiliated Hospital between November 2012 and December 2019. Rates of women that were referred to further screening, fulfilled selection criteria and underwent the procedure were compared between patients with or without abdominal scars. We evaluated the treatment parameters of the two groups and used linear regression model predict non-perfused volume (NPV) at the end of the process. RESULTS: Out of 701 patients, 21.8% were suitable for MRgFUS. Women with scars had significant lower NPV compared with women without scars (60% versus 82.4%, p = 0.021). No serious adverse events were reported in both groups. Linear regression models showed that fibroids' volume, stopping the treatment due to severe pain and the presence of abdominal scars had a statistically significantly negative effect on NPV (betas: -11.51, -6.96, and -6.29, p-values: <0.001, 0.003, and 0.007 respectively), while number of sonication had a statistically significantly positive effect on NPV (beta = 5.98, p = 0.011). CONCLUSION: Regardless of strict inclusion criteria, MRgFUS treatment is less efficient among women with abdominal scars, although still feasible for those who are interested in noninvasive option.

Cord blood androgen levels of females from same sex and opposite sex twins - A pilot study.

OBJECTIVE: Opposite-sex twins have shown behavioural and reproductive differences between females and males. These differences may be determined by higher intrauterine levels of androgens among females that were exposed to a male co-twin. The aim of this study was to compare cord blood androgen levels in females from same-sex and opposite-sex twins. DESIGN: A prospective study. In this pilot study, we compared cord blood androgens (DHEA-S, Δ-4 androstenedione, total testosterone-TT) and sex hormone-binding globulin (SHBG) levels in 20 females from same sex and 20 females from opposite-sex dichorionic diamniotic twins. We used generalized estimating equation (GEE) modelling to assess differences in cord blood androgens between females from same-sex twin pregnancies and females from opposite-sex twin pregnancies. PATIENTS: Twenty opposite-sex twin pairs (female-male twins) and 20 same-sex twin pairs (female-female). MEASUREMENTS: Cord blood total testosterone, Δ-4 androstenedione, DHEA-S and sex hormone-binding globulin (SHBG) levels. RESULTS: No difference in the levels of androgens as Δ-4 androstenedione, total testosterone and SHBG was identified between females that were exposed to a female co-twin compared with females that were exposed to a male co-twin. DHEA-S levels were significantly lower among females from opposite-sex twins compared with females from same-sex twins. CONCLUSIONS: Our preliminary data do not support the hypothesis that females exposed to male co-twins are exposed to higher levels of androgens in utero compared with females exposed to female co-twins. Further studies are needed to explain the reported behavioural and reproductive differences among opposite-sex twins.

Body mass index in relation to extracellular vesicle-linked microRNAs in human follicular fluid.

OBJECTIVE: To study whether increased body mass index is associated with altered expression of extracellular vesicle microRNAs (EV-linked miRNAs) in human follicular fluid. DESIGN: Cross-sectional study. SETTING: Tertiary-care university-affiliated center. PATIENT(S): One hundred thirty-three women undergoing in vitro fertilization (IVF) were recruited from January 2014 to August 2016. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): EV-linked miRNAs were isolated from follicular fluid and their expression profiles were measured with the use of the Taqman Open Array Human miRNA panel. EV-linked miRNAs were globally normalized and inverse-normal transformed. Associations between body mass index (BMI) and EV-linked miRNA outcomes were analyzed by means of multivariate linear regression and principal component analysis. RESULT(S): Eighteen EV-linked miRNAs were associated with an increase in BMI after adjusting for age, ethnicity, smoking status, and batch effects. Hsa-miR-328 remained significant after false discovery rate adjustments. Principal component analyses identified the first principal component to account for 40% of the variation in our EV-linked miRNA dataset, and adjusted linear regression found that the first principal component was significantly associated with BMI after multiple testing adjustments. Using Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we predicted gene targets of EV-linked miRNA in silico and identified PI3K-Akt signaling, ECM-receptor interaction, focal adhesion, FoxO signaling, and oocyte meiosis pathways. CONCLUSION(S): These results show that a 1-unit increase in BMI is associated with altered follicular fluid expression of EV-linked miRNAs that may influence follicular and oocyte developmental pathways. Our findings provide potential insight into a mechanistic explanation for the reduced fertility rates associated with increased BMI.

An optimized model for hCG stimulation of human mural granulosa cell culture.

Ovarian follicular development and ovulation in mammals is a highly-regulated process. Most of the current knowledge of ovarian processes was obtained from the studies of non-human models. Molecular studies on human ovarian processes suffer from lack of material and appropriate research tools. Mural granulosa cells (MGCs) culture is a major tool for studying the effect of different substances but a major problem for using these primary MGCs is their unresponsiveness to hCG stimulation at the time of oocyte retrieval. It is acceptable that MGCs regain responsiveness during days in culture but when the best time is and how to accelerate the regenerative process are unknown. The aim of the current study was to establish an optimized protocol which will provide a practical and efficient tool to examine the effect of LH/hCG on different downstream targets in luteinized MGCs. hCG effects were examined according to days in culture and hCG stimulation time. As read-out, we analyzed the gene expression of known hCG targets, protein production, and progesterone secretion. Our results show that with a daily medium exchange, the strongest effect was achieved already 4 days after seeding. On day 4, hCG stimulation triggers two major patterns of gene expression. Early induced genes were highly expressed 6-8 h after hCG, while 24 h of hCG stimulation was needed for late induced genes. Based on our results, we suggest daily medium exchange for 4 days before adding hCG and examine its effect 6 and 24 h later.

Extracellular microRNAs profile in human follicular fluid and IVF outcomes.

Encapsulated microRNAs (i.e., miRNAs within the extracellular vesicles, i.e., EV-miRNAs) have been detected in follicular fluid in both animal and human studies and different profiles have been associated with IVF cycle characteristics. However, limited studies to date have investigated other IVF outcomes, including fertilization status and embryo quality on day three". In this cohort, we performed a cross-sectional analysis on 126 women who contributed follicular fluid from a single follicle during a single IVF cycle. One hundred and ninety-two EV-miRNAs were assessed by univariable fold-change and multivariable logistic regression analyses. Hsa-miR-92a and hsa-miR-130b, were over-expressed in follicular fluid samples from oocytes that failed to fertilize compared to those that were normally fertilized. Additionally, hsa-miR-888 was over-expressed and hsa-miR-214 and hsa-miR-454 were under-expressed in samples that resulted in impaired day-3 embryo quality compared to top-quality day-3 embryos. After adjusting for confounders as BMI, smoking and total motile sperm, associations of these EV-miRNAs remained significant. In-silico KEGG pathway analyses assigned the identified EV-miRNAs to pathways of follicular growth and development, cellular signaling, oocyte meiosis, and ovarian function. Our findings suggest that EV-miRNAs may play a role in pathways of ovarian function and follicle development, which could be essential for understanding the molecular mechanisms that could lead to a successful pregnancy and birth.

Long-term outcome of MR-guided focused ultrasound treatment and laparoscopic myomectomy for symptomatic uterine fibroid tumors.

BACKGROUND: Fibroid tumors are the most common benign tumors in women of reproductive age. Treatment is usually indicated for those who are symptomatic, with different techniques being used. OBJECTIVE: The purpose of this study was to compare the long-term outcome of laparoscopic myomectomy with magnetic resonance-guided focused ultrasound for symptomatic uterine fibroid tumors. STUDY DESIGN: A cohort study was conducted on all patients with symptomatic uterine fibroid tumors who were admitted to a single tertiary care center and treated operatively with laparoscopic myomectomy or treated conservatively with magnetic resonance-guided focused ultrasound from January 2012 until January 2017. Assessment for further interventions and sustained fibroid-associated symptoms was performed, with the use of the Uterine Fibroid Symptom and Quality of Life symptom severity score. RESULTS: One hundred fifty-four women met the inclusion criteria. Complete follow-up evaluation was achieved for 64 women who underwent laparoscopic myomectomy and for 68 women who were treated by magnetic resonance-guided focused ultrasound. Follow-up time was similar for the 2 groups (median, 31 months [interquartile range, 17-51 months] vs 36 months [interquartile range, 24-41]; P=.95). The rate of additional interventions was 5 (7.8%) and 9 (13.2%), respectively (P=0.312). Similarly, the Uterine Fibroid Symptom and Quality of Life symptom severity score questionnaire score at follow-up interviews revealed comparable median scores of 17 (interquartile range, 12-21) vs 17 (interquartile range, 13-22) for laparoscopic myomectomy and magnetic resonance-guided focused ultrasound, respectively (P=.439). Analysis of each of the symptoms separately (bleeding, changes in menstruation, abdominal pain, bladder activity, nocturia, fatigue) did not change these findings, nor did a multivariate analysis. CONCLUSION: Satisfaction with long-term outcome and rate of reinterventions after magnetic resonance-guided focused ultrasound treatment or laparoscopic myomectomy for uterine fibroid tumors was comparable. Further larger randomized trials are needed to confirm these findings.

Outcome of magnetic resonance-Guided focused ultrasound surgery (MRgFUS) for FIGO class 1 fibroids.

OBJECTIVE: Intracavitary uterine fibroids and fibroids that distort the uterine cavity are associated with excessive vaginal bleeding and infertility. While intracavitary fibroids smaller than 4 cm are usually treated safely by operative hysteroscopy, larger fibroids may require multiple surgeries or more extensive surgery with possible damage to the integrity of the uterine wall. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive approach for treating uterine fibroids, mainly the intramural type. We present the outcome of MRgFUS treatment for intracavitary fibroids (FIGO class 1) in cases that could not be treated by hysteroscopy due to either fibroid size or patient refusal. (Canadian Task Force II-1). STUDY DESIGN: A retrospective cohort study from a single tertiary referral center. A total of 68 patients were treated by MRgFUS for symptomatic uterine fibroids from January 2013 to December 2016. Six of them had FIGO class 1 fibroids. Adverse effects and short- and long-term outcomes (quality of life issues and need for additional surgical intervention) were assessed during ambulatory clinic visits and by phone interviews. RESULTS: The mean ±â€¯SD fibroid volume on MRI screening was 86.3 ±â€¯60.9 cm3. Six of those patients underwent the procedure (mean age 40.5 ±â€¯5.6 years, range 33-48). The follow-up duration was 24.1 ±â€¯12.0 months. Four patients were not interested in future fertility and did not undergo additional treatment, while the two who planned to conceive underwent another surgical intervention (one underwent operative hysteroscopy after reduction of fibroid size and the other underwent laparoscopic myomectomy). CONCLUSION: This preliminary study shows that MRgFUS can be a feasible treatment option for FIGO class 1 uterine fibroids. Shrinkage of fibroids by MRgFUS can obviate or facilitate subsequent surgical intervention in selected cases.

Dibutyl phthalate impairs steroidogenesis and a subset of LH-dependent genes in cultured human mural granulosa cell in vitro.

Exposure to di-butyl phthalate (DBP) exerts negative effects on female fertility in animal models, but human studies remain limited. Here, the effects of DBP exposure on mural granulosa cell function were investigated in primary cultures from women undergoing in vitro fertilization. Cultured cells treated with various doses of DBP (0, 0.01µg/mL, 0.1µg/mL, 1µg/mL, 10µg/mL, or 100µg/mL) for 48h were assessed using enzyme-linked immunosorbent assay and qRT-PCR. Treatment with 100µg/mL DBP resulted in significantly lower 17ß-estradiol and progesterone production (p<0.01). It also resulted in altered mRNA expression of steroidogenic, angiogenic, and epidermal growth factor-like growth factor genes: CYP11A1 (p<0.001), CYP19A1 (aromatase) (p<0.001), VEGF-A (p<0.02), BTC (p=0.009), and EREG (p=0.04). StAR expression was impaired after exposure to both 10 and 100µg/mL (p<0.03 and p<0.001, respectively). Our results indicate that in vitro exposure of granulosa cells to high doses of DBP alters cell functions.

Standard human chorionic gonadotropin versus double trigger for final oocyte maturation results in different granulosa cells gene expressions: a pilot study.

OBJECTIVE: To investigate the messenger RNA (mRNA) expression of reproduction-related genes in granulosa cells (GCs) of patients triggered with hCG compared with patients triggered with GnRH agonist and hCG (double trigger) for final oocyte maturation. DESIGN: Granulosa cells were obtained at the time of oocyte retrieval, and gene expression was analyzed using quantitative real-time polymerase chain reaction. SETTING: Referral center. PATIENT(S): Fifteen women undergoing controlled ovarian hyperstimulation for IVF who received hCG for final follicular maturation and in a subsequent IVF cycle received double trigger. INTERVENTION(S): Granulosa cells collection. MAIN OUTCOME MEASURE(S): The expression of genes related to ovarian hyperstimulation syndrome, gap junction, and epidermal-like growth factor in GCs. RESULT(S): The mRNA expressions of amphiregulin (2.1 vs. 1, arbitrary unit) and epiregulin (2.5 vs. 1, arbitrary unit) were significantly higher in the double trigger group compared with the hCG group. We found no difference in luteinizing hormone receptor and follicle stimulating hormone receptor mRNA expressions between the two groups. Moreover, although the mRNA expression of pigment epithelium-derived factor (1.5 vs. 1, arbitrary unit) was significantly higher in the double trigger group, no between-group differences were observed in the expression of vascular endothelial growth factor and GnRH receptor. The mRNA expression of conexin43 in cumulus cells (0.7 vs. 1, arbitrary unit) was significantly lower in the double trigger group compared with the hCG group. CONCLUSION(S): Our findings suggest that the decreased expression of conexin43 and the increased expression of epiregulin and amphiregulin in the GCs from patients receiving the double trigger may explain the suggested improved oocyte and embryo quality related to the double triggering group.

Does BPA alter steroid hormone synthesis in human granulosa cells in vitro?

STUDY QUESTION: Does Bisphenol A (BPA) impair steroid hormone production in human luteinized granulosa cells in vitro? SUMMARY ANSWER: At supra-physiological concentrations, BPA alters progesterone and estradiol synthesis in vitro and significantly reduces the mRNA and protein expression levels of three genes encoding steroidogenesis enzymes. WHAT IS KNOWN ALREADY: In IVF patients, the effects of BPA exposure on cycle outcome are controversial. Previous animal studies have shown that granulosa cell steroid hormone synthesis is compromised after BPA exposure, but their findings have been difficult to replicate in humans due, in part, to the low availability of discarded biological material. STUDY DESIGN, SIZE, DURATION: Luteinized granulosa cells obtained from 44 fertile and infertile patients undergoing in vitro fertilization were cultured for 48 h with different concentrations of BPA (0, 0.2, 0.02, 2.0, 20 µg/ml). PARTICIPANTS/MATERIALS, SETTING, METHODS: Culture medium and total RNA extracted from the luteinized granulosa cells were examined for estradiol and progesterone levels as well as mRNA and protein expression of steroidogenesis enzymes, using enzyme immunoassays, real-time PCR and western blots. MAIN RESULTS AND THE ROLE OF CHANCE: Treatment of granulosa cells with 2 or 20 µg/ml BPA for 48 h resulted in significantly lower progesterone biosynthesis (P < 0.005 and <0.001, respectively). Estradiol production was significantly altered only after incubation with 20 µg/ml of BPA (P < 0.001). These concentrations also significantly reduced the mRNA levels of 3ß-hydroxysteroid dehydrogenase (3ß-HSD), CYP11A1 and CYP19A1 without affecting StAR and 17ß-hydroxysteroid dehydrogenase mRNA expression. Similarly, 3ß-HSD, CYP11A1 and CYP19A1 protein levels were reduced after administration of 20 µg/ml BPA. Lower BPA concentrations similar to, and up to 100 times, the concentrations measured in human follicular fluid, serum and urine did not alter steroidogenesis in primary granulosa cell cultures. LIMITATIONS, REASONS FOR CAUTION: This was an in vitro study investigating the effects of acute exposure (48 h) of BPA on discarded material. As such, the model may not accurately reflect the effect of BPA on the physiological events of follicular steroid hormone synthesis in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our results show that in vitro exposure to BPA at low doses does not affect granulosa cells steroidogenesis. Combined with recent in vivo studies, these data can be reassuring but further studies are needed to assess the effects of chronic exposure to BPA on ovarian steroidogenesis. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by grant number 1936/12 from the Israeli Science Foundation (ISF). The authors have no conflict of interest.

Modifying the luteal phase support in natural cycle frozen-thawed embryo transfer improves cycle outcome.

With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250 mcg) and the other of GnRH-agonist (triptorelin 0.1 mg), on the day of transfer and 4 d later, respectively. While the patients' clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive ß-hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4 d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.

Co-administration of GnRH-agonist and hCG, for final oocyte maturation (double trigger), in patients with low proportion of mature oocytes.

OBJECTIVE: Human chorionic gonadotropin (hCG) is usually used at the end of controlled ovarian hyperstimulation (COH), as a surrogate LH surge, to induce final oocyte maturation and resumption of meiosis. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation - 40 and 34 h prior to OPU, respectively (double trigger) was suggested to improve IVF outcome in patient with genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger might improve the proportions of metaphase-II (MII) oocytes in patients with low proportion of mature oocytes (<66%) per number oocytes retrieved. PATIENTS AND METHODS: We compared the stimulation characteristics of 12 IVF cycles, which include the cycle with the double trigger to the same patients' previous IVF attempt, triggered with hCG-only. RESULTS: Patients who received the double trigger (study group) had a significantly higher number of mature oocytes - MII (6.5 versus 3.6 p < 0.008), number of embryos transferred (2.4 versus 1.1 p < 0.03), a significantly higher proportions of MII oocytes per number of oocytes retrieved (69.7% versus 47.1% p < 0.03) and a higher number of top quality embryos (3.1 versus 1 p < 0.02), as compared to their previous control cycles (hCG-only trigger). Six pregnancies were recorded in the study group and none in the control group. CONCLUSIONS: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) improves IVF outcome in patients with high proportion of immature oocytes.

Does bariatric surgery improve ovarian stimulation characteristics, oocyte yield, or embryo quality?

BACKGROUND: Obesity is a major global health concern associated with multiple co-morbidities. Bariatric surgery has been considered a good treatment option in cases of morbid obesity. This preliminary study aims to investigate the effect of bariatric surgery on ovarian stimulation characteristics and IVF treatment cycle outcome. METHODS: A retrospective study that was performed in a tertiary, university-affiliated medical center and included all patients who underwent IVF treatment both before and after bariatric surgery. Data on ovarian stimulation variables of IVF treatment cycle prior and following the bariatric surgery were reviewed and compared. RESULTS: From January 2005 to June 2014, seven women fulfilled the inclusion criteria. After the operation, BMI was significantly reduced (mean ± SD) (43.1 ± 3.3 vs. 29.6 ± 7.33, p = 0.018), as was the number of gonadotropin ampoules required during stimulation (69.3 ± 10.5 vs. 44.5 ± 17, p = 0.043). No between-cycle differences were observed in peak estradiol level, the number of oocytes retrieved, and percentage of mature oocytes. CONCLUSIONS: To the best of our knowledge, this preliminary case series is the first comparison of IVF cycle characteristics prior to and following bariatric surgery. The operation seems to reduce treatment costs without affecting oocyte or embryo quality. Further large studies are required to establish the surgery's effect on IVF outcome among infertile women.

Co-administration of GnRH-agonist and hCG for final oocyte maturation (double trigger) in patients with low number of oocytes retrieved per number of preovulatory follicles--a preliminary report.

BACKGROUND: Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation- 40 and 34 hours prior to OPU, respectively (double trigger) was suggested as the treatment of genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger improves the number of oocytes retrieved in patients with low (<50%) number of oocytes retrieved per number of preovulatory follicles. METHODS: In this proof of concept cohort historical study, we compared the stimulation characteristics of 8 IVF cycles, which include the double trigger to the patients' previous IVF attempt, triggered with hCG-only. RESULTS: Patients who received the double trigger (study group) had a significantly higher number of oocytes retrieved, number of 2PN, number of embryos transferred and significantly higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, with a tendency toward a higher number of TQE, as compared to their previous cycles (hCG-only trigger). Three ongoing clinical pregnancies were recorded in the study group and none in the hCG-only trigger group. CONCLUSIONS: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (double trigger), is suggested as a valuable new tool in the armamentarium for treating patients with low/poor oocytes yield despite an apparently normal follicular development and E2 levels and in the presence of optimal hCG levels on the day of OPU.

[Obesity, bariatric surgery and future fertility].

Obesity is an increasingly widespread health problem. In addition to comorbidities such as diabetes, hypertension, dyslipidemia and cardiovascular disease, obesity has a significant impact on reproductive life, including infertility, miscarriages and high prevalence of pregnancy complications. The present review describes the possible benefits of bariatric surgery regarding fertility and pregnancy outcome. It is well established that bariatric surgery leads to regular ovulatory cycles and improves spontaneous conception rates in obese women. While pregnancy after bariatric surgery is safe and associated with reduced pregnancy complications, pregnant women following bariatric surgery are still at high risk for preterm births and small dimensions of gestational age offsprings. The optimal interval that should be kept between surgery and subsequent pregnancy is controversial, with recent studies emphasizing the importance of nutritional balance rather than the time from surgery to conception as being the most important determinant. Strict peri-conceptional surveillance is mandatory in order to prevent nutritional deficiencies and for the early diagnosis of abnormal fetal growth.

HCG (1500IU) administration on day 3 after oocytes retrieval, following GnRH-agonist trigger for final follicular maturation, results in high sufficient mid luteal progesterone levels - a proof of concept.

BACKGROUND: Controlled ovarian hyperstimulation (COH) which combining GnRH antagonist co-treatment and GnRH agonist trigger with an additional 1500 IU hCG luteal rescue on day of oocytes retrieval, has become a common tool aiming to reduce severe ovarian hyperstimulation syndrome (OHSS). In the present, proof of concept study, we evaluate whether by deferring the hCG rescue bolus for 3 days, we are still able to rescue the luteal phase. METHODS: Patients undergoing the GnRH-antagonist protocol, who were considered at high risk for developing severe OHSS and received GnRH-agonist for final oocyte maturation, were included. For luteal phase support, all patients received an "intense" luteal support. Those who had no signs of early moderate OHSS on day 3 after oocytes retrieval were instructed to inject 1500 IU of HCG bolus (hCG group). Ovarian stimulation characteristics and mid luteal progesterone levels were compared between those who received the HCG bolus and those who did not. RESULTS: Eleven IVF cycles were evaluated, 5 in the hCG group and 6 in the intense luteal support only group. While no in-between group differences were observed in ovarian stimulation characteristics, significantly higher mid luteal progesterone levels (>127 nmol/L vs 42.1 ± 14.5 nmol/L, respectively) and a non-significant increase in pregnancy rate (40% vs 16.6%, respectively), were observed in those who receive the hCG bolus compared to those who did not. CONCLUSIONS: hCG luteal rescue should be offered 3 days after oocytes retrieval only to those patients with no signs of early moderate OHSS. Further studies are required to elucidate the appropriate regimen of luteal HCG administration in patients undergoing final follicular maturation with GnRH-agonist.

Is the modified natural in vitro fertilization cycle justified in patients with "genuine" poor response to controlled ovarian hyperstimulation?

OBJECTIVE: To examine whether patients with poor ovarian response (POR) during conventional IVF/intracytoplasmic sperm injection (ICSI) treatment cycle may benefit from a modified natural cycle (MNC)-IVF. DESIGN: Cohort historic study. SETTING: Tertiary, university-affiliated medical center. PATIENT(S): One hundred eleven patients with POR, defined according to the Bologna criteria, who underwent a subsequent MNC-IVF within 3 months of the previous failed conventional IVF/ICSI cycle. The elimination of bias in this selection, for the purposes of this study, was achieved by including only a subgroup of "genuine" poor responder patients, those who yielded up to three oocytes after controlled ovarian hyperstimulation (COH) with a minimal gonadotropin daily dose of 300 IU. INTERVENTION(S): Modified natural cycle IVF protocol with GnRH antagonist (GnRH-a) supplementation. Gonadotropin-releasing hormone antagonist treatment was started when a follicle of 13 mm was present. Two to three ampules of hMG were coadministered daily during the GnRH-a treatment. MAIN OUTCOME MEASURE(S): Live birth rate, pregnancy rate (PR), number of oocytes retrieved, and number of embryos transferred. RESULT(S): Live birth rate in "genuine" poor ovarian responders was <1%. Furthermore, in the subgroup of patients with POR who underwent a previous conventional IVF/ICSI cycle with a yield of only one oocyte, no pregnancies were achieved during the MNC-IVF cycle. CONCLUSION(S): Modified natural cycle-IVF is of no benefit for genuine poor ovarian responders and the option of egg donation should be seriously considered for this population.

MR-guided focused ultrasound (MRgFUS) is effective for the distinct pattern of uterine fibroids seen in African-American women: data from phase III/IV, non-randomized, multicenter clinical trials.

BACKGROUND: Uterine fibroids are common among women at the reproductive age. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel and a conservative treatment for symptomatic cases. The aim of the study was to evaluate the efficacy of MRgFUS in African-American (AA) women compared with that in non-African-Americans (non-AA). METHODS: A single-armed phase IV study was conducted to establish the efficacy of treatment in AA women. Comparison of patient, fibroid, and treatment characteristics from this trial was compared with that of the previously published phase III trial. Both studies were approved by the IRB of each medical center. RESULTS: Sixty-three AA and 59 non-AA women were treated with MRgFUS. Although AA women had a different pattern of disease, outcomes were similar in both groups. AA patients had a significant higher total number of fibroids compared with non-AA (median 6.0, interquartile range (IQR) 3.0-10.0 vs. 2.0, IQR 1.0-4.0, respectively, p < 0.001), although their total fibroid volume was significantly smaller (median 196.9 cm(3), IQR 112.8-415.3 cm(3) vs. 394.8 cm(3), IQR 189.8-674.4 cm(3), respectively, p < 0.001). AA women were younger compared with non-AA (mean ± SD 43.4 ± 5.1 vs. 46.3 ± 4.1 years of age, respectively, p = 0.001) when they presented for treatment. The rate of alternative treatments as well as fibroid-associated symptoms at follow-up time points (3, 6, 12, 24, and 36 months, period following MRgFUS treatment) did not differ according to race (p ≥ 0.62). CONCLUSION: Despite differences in the pattern of fibroid disease, MRgFUS for uterine fibroids has a similar efficacy for AA women compared with non-AA women.