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Aim: To investigate the impact of letrozole cotreatment progestin‐primed ovarian stimulation (PPOS) (Le PPOS) in controlled ovarian stimulation (COS) and the pregnancy outcomes in frozen–thawed embryo transfer cycles. Methods: This retrospective cohort study included women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). A total of 2575 cycles were included (1675 in the Le PPOS group and 900 in the PPOS group). The primary outcome was the clinical pregnancy rates. The secondary outcome was the live birth rates. Results: In this study, propensity score matching (PSM) was performed to create a perfect match of 379 patients in each group. After matching, the numbers of oocytes retrieved, mature oocytes, fertilization, and clinical pregnancy rates were more favorable in the Le PPOS group than in the PPOS group (all p < 0.05). The multivariable analysis showed that the clinical pregnancy rate was higher in the Le PPOS than in the PPOS group (odds ratio = 1.46, 95% confidence interval: 1.05–2.04, p = 0.024) after adjusting for potentially confounding factors (age, anti‐Müllerian hormone levels, antral follicular count, the type of embryo transferred, number of transferred embryos, body mass index, and follicular stimulating hormone and estradiol levels on starting day). Conclusions: This retrospective study with a limited sample size suggests that the Le PPOS protocol might be an alternative to the PPOS protocol in women undergoing COS and could lead to better pregnancy outcomes. The results should be confirmed using a formal randomized controlled trial. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was that to assess the allelic and genotype frequencies of nine prothrombotic gene variants in patients with a history of pregnancy loss and recurrent pregnancy loss (RPL). Women who underwent assisted reproductive technology (ART) with ongoing pregnancy and those with recurrent implantation failure (RIF) were also included. Methods: Nine prothrombotic gene variants were evaluated: factor V Leiden (FVL), factor V, H1299R variant (FVR2), factor II (FII) G20210A, methylene‐tetrahydrofolate reductase (MTHFR) C677T and A1298C, beta‐fibrinogen ‐455G>A, factor XIII (FXIII) V34L, human platelet antigen‐1 (HPA‐1) L33P variants, and plasminogen activator inhibitor‐1 (PAI‐1) 4G/5G. The following study groups were assessed: (1) women who experienced one (n = 334) or two (n = 264) episodes of pregnancy loss; (2) 468 women who experienced RPL; (3) 214 women who underwent ART followed by ongoing pregnancies; and (4) 282 women who experienced RIF after ART, that is, three or more consecutive implantation failures following high‐quality embryo transfers to the uterus with an appropriate endometrium. As control group, 430 subjects from the general population were enrolled. Results: FVL, the ‐455G>A variant of beta‐fibrinogen, and PAI‐1 4G were associated with a higher risk of developing RPL compared with the general population. Furthermore, FVL, FVR2, FII G20210A and MTHFR C677T conferred a significantly higher risk of RIF in women who performed ART compared with the general population. No statistical differences between the general population and other study groups were observed. Conclusions: Specific prothrombotic genetic variants are more frequently expressed in women with RPL and RIF, supporting their role in the development of polimicrothrombosis and impairing the invasion during embryo implantation. Synopsis: Prothrombotic gene variants are associated with increased risk of recurrent implantation failure and recurrent pregnancy loss compared with the general population. [ABSTRACT FROM AUTHOR]

Aim: Reduced responses to controlled ovarian stimulation (COS) after radical trachelectomy (RT) have been previously reported. We aimed to assess the effect of RT on ovarian reserve by measuring anti‐Müllerian hormone (AMH) levels before and after the procedure in this prospective study. Methods: We included 12 patients who underwent RT between September 2019 and December 2021 in this study. Serum AMH levels were measured preoperatively, 1 month postoperatively, and 6 months postoperatively. Differences in the AMH levels were assessed using a paired t‐test. Results: The median age of the patients was 30.6 years, and the median follow‐up time was 30.1 months. AMH levels at 1 and 6 months postoperatively did not show a consistent trend. At 1 month postoperatively, the average AMH level decreased insignificantly but returned to preoperative levels at 6 months. The differences in AMH levels before and after RT were insignificant. Conclusion: Our findings indicate that RT did not affect ovarian reserve as measured by AMH levels. However, the relationship between unchanged ovarian reserve and reduced response to COS remains unclear. Further research with larger sample sizes and additional measures of ovarian function is needed to corroborate these results and investigate the long‐term effects of RT on ovarian reserve. Understanding these mechanisms will help guide surgical practices and provide patients with valuable information about their reproductive outcomes after RT. [ABSTRACT FROM AUTHOR]

Anti‐Müllerian hormone (AMH) is produced by granulosa cells of the antral follicles. It serves as a promising biomarker for ovarian reserve and responsiveness to ovarian stimulation in humans and domestic animals. This study aimed to validate the AMH Gen II enzyme‐linked immunosorbent assay (ELISA) and correlate ovarian structures with serum AMH concentrations after stimulation treatment in clouded leopards (Neofelis nebulosa). Serum samples were collected from 12 women (age 6.21 ± 3.56 years), and serum AMH concentrations were analysed using AMH Gen II ELISA. The animals were divided into two groups based on ovarian structures [preovulatory follicles (>2 mm) and/or corpora hemorrhagica] along with the presence of uterine tonicity visualized laparoscopically around the time of ovulation. Animals that exhibited these reproductive features were identified as the responder group (n = 9, aged 7.59 ± 2.96 years), whereas those lacking the corresponding features were assigned to the nonresponder group (n = 3, aged 2.06 ± 0.53 years). The intra‐assay coefficient of variation (CV) and interassay CV was 3.56% and 7.75%, respectively. The linearity of AMH dilution was confirmed (r2 =.998), and the percentage of recovery ranged from 93% to 115%. The results demonstrated that overall serum AMH concentrations around the time of ovulation were negatively correlated with age (rs = −.692, p =.013). However, serum AMH concentrations were not correlated with the average number of ovarian structures (rs = −.535, p =.074). Thus, AMH Gen II ELISA was validated in clouded leopards. Around the time of ovulation, serum AMH decreased with advancing age and ovarian responsiveness cannot be evaluated using serum AMH. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate the value of follicular fluid fetuins‐A and ‐B to predict successful IVF and pregnancy outcomes in infertile women with poor, normal, and high ovarian reserve. Methods: The follicular fluid of 96 infertile women who underwent intra‐cytoplasmic sperm injection (ICSI) procedure was analyzed. Fetuins‐A and ‐B levels were examined and compared in those who could achieve pregnancy and those who could not. Receiver operating characteristic curve analyzes were used to determine cut‐off and statistically significant associations for fetuins‐A and ‐B. Results: Follicular fluid fetuin‐A levels were higher in cases with weak ovarian reserve (OR) (p < 0.05) and higher in patients who did not achieve clinical pregnancy (p < 0.05). Conversely, the follicular fluid fetuin‐B levels were lower in cases with poor OR (p < 0.05) and were lower in patients who did not achieve a clinical pregnancy (p < 0.05). A follicular fluid fetuin‐A concentration ≤ 19.12 ng/mL had a sensitivity and specificity of 94.74% and 93.1%, respectively, at predicting clinical pregnancy. While the follicular fluid fetuin‐B concentration >24.7 ng/mL had sensitivity and specificity of 71.1% and 51.7%, respectively, for clinical pregnancy prediction. Conclusion: Overall, high levels of follicular fluid fetuin‐A may be independently associated with unsuccessful IVF irrespective of OR grouping. A low level of follicular fetuin‐B was also associated with failed IVF. The sensitivity and specificity were found to be higher for fetuin‐A in predicting clinical pregnancy. Therefore, the follicular fluid fetuin‐A may be more predictive for successful IVF and clinical pregnancy outcomes than follicular fluid fetuin‐B. [ABSTRACT FROM AUTHOR]

Background: Preservation of female fertility is a relatively new field in medicine that has grown very rapidly in recent decades. At the beginning, embryo freezing remained the most effective technique. Thereafter, cryopreservation of oocytes and ovarian tissue was considered a secure tool in human fertility preservation. Storage of cortical ovarian tissue is moreover relevant for children, prepubertal girls, and adult patients who cannot benefit from cryopreservation of oocytes.Objective: To analyze and review recent and relevant scientific literature on medical and social reasons for preservation of fertility.Methods: The review was conducted based on articles identified from PubMed databases using keywords.Main Results: Oocyte vitrification allows women to preserve their fertility without the need for fertilization. Nowadays, thousands of healthy children have been born from this procedure. Occurrence of pregnancy depends on two main factors: the number of mature oocytes in storage and the age of the patient at the time of vitrification. Numerous adaptations have been developed to suit the ovarian stimulation regiments to patients with cancer. In young prepubertal girls, freezing of ovarian tissue remains the best and only option.Conclusion: Oocyte vitrification therefore appears to be the gold standard technique of preserving fertility in young women. [ABSTRACT FROM AUTHOR]

This retrospective study compares four different strategies for managing poor ovarian response (POR), namely, conventional stimulation (300 IUs) IVF–fresh embryo transfer (CONVF), mild stimulation (150 IUs) IVF–fresh embryo transfer (MILDF), mild stimulation embryo banking (MILDB), and embryo banking in natural cycles (NATB). In total, 796 POR patients were considered eligible. Statistical analysis revealed a shorter duration of stimulation and a lower required amount of gonadotropins in MILDF compared with CONVF (9.34 ± 1.17 versus 10.37 ± 1.14; 1402 ± 176 versus 3110 ± 343, P < 0.001). Comparing MILDF and MILDB, a higher number of available oocytes and embryos was observed in MILDB (2.36 ± 1.15 versus 6.58 ± 1.11; 1.72 ± 1.02 versus 3.51 ± 0.61, P < 0.001). Moreover, the MILDB presented with a lower number of required oocyte retrievals and a higher number of oocytes per oocyte retrieval compared with NATB (3.90 ± 1.56 versus 7.15 ± 1.80; 1.95 ± 0.74 versus 0.89 ± 0.20, P < 0.001). Data indicate that MILDF is equally efficient and associated with a shorter duration of stimulation and a lower required amount of gonadotropins compared with CONVF. Embryo accumulation may be more efficient compared with a fresh embryo transfer. MILDB may be a more efficient approach compared with NATB. To conclude, embryo accumulation following mild stimulation appears to form the optimal strategy for POR management. More studies are needed to verify these conclusions. [ABSTRACT FROM AUTHOR]

Introduction: Frozen embryo transfer is associated with a higher rate of live birth and a lower risk for ovarian hyperstimulation syndrome in women with polycystic ovary syndrome (PCOS) compared with fresh embryo transfer. The aim of this study is to assess the optimal endometrial preparation protocol for women with PCOS undergoing frozen embryo transfer. Material and methods: We conducted a historical cohort analysis of 1720 women with PCOS who underwent the "freeze‐all" strategy between August 2014 and August 2017 because of their high risk for ovarian hyperstimulation syndrome. Three endometrial preparation protocols were used: natural cycle (NC; n = 191), which relies on the dominant follicle to secrete estrogen that then promotes endometrial growth; ovarian stimulation (OS; n = 96), which induces follicle growth using low doses of human menopausal gonadotropin; and hormone replacement (HRT; n = 1433), which uses exogenous estradiol to promote endometrial growth. The primary outcome was live birth. Results: For women who received a single embryo transfer, the live birth rates for the NC, OS, and HRT groups were 62.4%, 65.0%, and 52.2%, respectively. The live birth rate in the HRT group was significantly lower than that seen in the OS and NC groups (P =.009). The clinical pregnancy rates of the three groups were 72.3%, 73.8%, and 64.9%, respectively; this difference did not reach statistical significance (P =.071). Conclusions: The rate of live birth with the NC and OS regimens was higher than with the HRT protocol in women with PCOS who undergo single‐blastocyst frozen embryo transfer. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the estradiol/oocyte ratio (E2/O) can predict ovarian response and pregnancy outcomes. Methods: This is a retrospective cohort study on 1838 individuals undergoing in vitro fertilization with a depot gonadotropin‐releasing hormone agonist (GnRH‐a) long protocol. The patients were grouped by the quartiles of E2/O: <131.2, 131.2–178.0, 178.0–242.9, and >242.9 pg/mL. ANOVA and χ2 test with the Bonferroni adjustment were used for statistical analysis. Results: With the rise of E2/O, the MII oocyte rate increased, whereas the number of oocytes retrieved decreased. The number of MII oocytes, fertilization rate, and the number of high‐grade embryos were similar among the four groups. There were no differences in live‐birth rate, clinical pregnancy rate, ectopic pregnancy rate, and miscarriage rate, but there was a trend towards a higher miscarriage rate in the patients with E2/O between 131.2 and 242.9 pg/mL. Conclusion: E2/O indicates the percentage of MII oocytes, but not the quality of an individual follicle. E2/O does not predict live birth in a depot GnRH‐a long protocol; however, there is a trend towards a higher risk for miscarriage in the patients with E2/O between 131.2 and 242.9 pg/mL. Estradiol/oocyte ratio predicts the MII oocyte percentage, but not the quality of an individual oocyte or pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Aim: To identify which positive prognostic parameters contribute to successful treatment outcomes and the probability of pregnancy by analyzing the results of infertile couples underwent ovulation stimulation (OS) and intra‐uterine insemination (IUI) in our clinic. Methods: Five hundred and nineteen couples who underwent OS‐IUI treatment because of a mild–moderate male factor, unexplained infertility, or anovulation were retrospectively analyzed. The data collected included patient demographics, cycle characteristic, sperm parameters and pregnancy rates. The main outcome measure was pregnancy rate (PR). Results: Our overall PR was 17.72% (n = 92). In women who did not achieve pregnancy, age, BMI and duration of infertility were significantly higher (P < 0.001, P < 0.001 and P = 0.03, respectively). The IUI indications of higher PR were unexplained infertility (P = 0.018) and primary infertility (P = 0.003). AFC was significantly lower and the total dosage of gonadotropins was significantly higher in women who did not achieve pregnancy (P = 0.001 and P = 0.017, respectively). The number of progressive motile spermatozoa inseminated and the morphology were significantly higher in women who did not achieve pregnancy (P = 0.056 and P = 0.001, respectively). Female age ≤ 30 (OR = 0.87; 95% CI: 0.81–0.95; P < 0.01), BMI ≤23.3 kg/m2 (OR = 0.87; 95% CI: 0.80–0.95; P = 0.002) and AFC > 9 (OR = 1.07; 95% CI: 1–1.15; P = 0.034) increase the pregnancy. Conclusion: Younger women, especially those with unexplained infertility, primary infertility, shorter duration of infertility, normal ovarian reserve, higher motile spermatozoa inseminated and sperm morphology, could benefit from OS‐IUI. [ABSTRACT FROM AUTHOR]

We are now in the beginning of the fifth decade of in vitro fertilization (IVF) with more than ten million children born and an annual growth rate of half a million. It was recently found that there is a sevenfold increase in the incidence of pulmonary embolism (PE) during the first trimester of an IVF pregnancy as compared to spontaneous pregnancy. PE is a major cause of maternal mortality, and it is thus of outmost importance to understand the pathophysiological mechanism. The oestrogen surge during the ovarian stimulation has been hypothesized to be the initiating pathophysiological event. A support of this is a current report showing that embryo transfer performed directly after ovarian stimulation increased the risk of PE more than eightfold, whereas no such increase was noted after delayed embryo transfer. This increased risk coincides with a persisting increased oestrogen level. Further reported cardiovascular problems are arterial thromboses, pre‐eclampsia and gestational hypertension. Global haemostasis tests change in the direction of increased coagulability, but mostly within normal limits. Cell‐bound haemostasis and in particular platelet activation are less studied. However, a major increase in the number of microvesicles (MVs) and markers indicating platelet activation was reported during ovarian stimulation. We now need longitudinal data concerning haemostatic variables that extends into the first trimester. A major research focus should be to identify biomarkers that could be used already before instigation of IVF. Another way to avoid risk could be to delay embryo transfer by adapting a freeze‐all strategy. [ABSTRACT FROM AUTHOR]

Fertility preservation in women with Turner syndrome is highly controversial. Some strongly recommend freezing of ovarian tissue at a young age, others do not. The controversy is partly due to different perspectives and professions. Biologists prefer to freeze young ovaries with high follicle density, reproductive physicians want to avoid risky operations and iatrogenic infertility by removing one ovary, and cardiologists and obstetricians warn against the risks of later pregnancies. Accordingly, fertility preservation in young women with Turner syndrome is more than just the freezing of ovarian tissue or oocytes. Fertility preservation requires a balanced decision considering the conservation of fertility, the protection of reproductive health, and future health consequences. Therefore, fertility preservation strategies should be based not only on the individual ovarian reserve but also on the genotype and the expected cardiac health status to decide what is the best option: to freeze tissue or alternatively to wait and see. [ABSTRACT FROM AUTHOR]

Background: Translation of findings from randomised controlled trials (RCT), the foundation of evidence‐based medicine, into clinical practice requires an understanding of relationships between patient characteristics, treatment practices and outcomes. We propose a novel technique, External Validity Analysis (EVA), to evaluate applicability of findings from a large RCT, comparing baseline characteristics, interventions and outcomes between the RCT and a large clinical database. Aim: To perform EVA of the findings of a randomised controlled trial (ESTHER‐1) to a population in an Australian clinic setting. To demonstrate this method, we evaluated the discordance in first cycle follicle‐stimulating hormone (FSH) exposure and outcomes between the two populations, to inform clinical practice. Materials and Methods: In this retrospective, descriptive analysis, we compared practices and outcomes between the follitropin alfa 'conventional' dosing arm of the ESTHER‐1 trial and a selected comparable clinic subpopulation of patients who underwent controlled ovarian stimulation using FSH. Results: Mean FSH exposure was 34% higher in the clinic subpopulation than in the trial subpopulation, resulting in higher average ovarian response without improving the likelihood of clinical pregnancy or live birth. Conclusions: EVA allowed for the comparison of a trial population with a selected clinic population with similar characteristics. With respect to FSH consumption, this analysis revealed higher exposure to FSH in the clinic setting without a corresponding benefit. The comparison reveals population differences as well as the potential to improve clinical outcomes through a reappraisal of current practices and objectives in gonadotropin dose selection. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) can be found in ovarian tissues. This study compared HBV DNA levels in follicular fluid collected during oocyte retrieval with paired serum samples in HBV carriers after ovarian stimulation during IVF treatment for infertility. Sixty‐four HBV carrier women referred to the Assisted Reproductive Units of two Hong Kong hospitals were recruited. At oocyte retrieval, the follicular fluid aspirated from the first follicle was collected for study. In 22 women, the first follicular fluid sample from both ovaries was similarly collected and studied. These women were also tested for liver function test and HBeAg. In 28 (43.8%) women, HBV DNA was detected in follicular fluid and the level correlated with serum levels (Spearman's correlation P <.001). There was concordant detection of HBV DNA in both ovaries, and the levels were significantly correlated (Spearman's correlation P =.029). In 40% of women with FF HBV DNA, the follicular fluid:serum ratio was >1.0, suggesting stimulation of HBV replication. These women also had significantly different liver function test results. Increased HBV replication exists in 40% of women with HBV DNA detected in follicular undergoing ovarian stimulation during IVF treatment. [ABSTRACT FROM AUTHOR]

Aim: We evaluated and compared the clinical and pathological differences between pregnant and non‐pregnant women with adnexal torsion. Methods: We retrospectively reviewed 239 women with adnexal torsion from January 2006 to December 2015 in a tertiary hospital. The clinical and pathological differences between pregnant and non‐pregnant women who underwent surgery for adnexal torsion were analyzed. Results: The most common pathologies were corpus luteum cysts in pregnant women and dermoid cysts in non‐pregnant women. Eight of the pregnant women (24.2%) had a history of exogenous ovarian stimulation, and their episodes were only caused by corpus luteum or a stimulated ovary. In pregnant women, 72.7% of the torsion occurred before the 14th week of gestation. Conclusion: The common pathology causing adnexal torsion was different, depending on the pregnancy status. Exogenous ovarian stimulation increases the risk of adnexal torsion, and the majority of episodes occurred in the first trimester in pregnant women. [ABSTRACT FROM AUTHOR]

Purpose: We asked whether the relationship between anti‐Műllerian hormone (AMH) value and the response to ovarian stimulation (OS) might be AMH value‐related and differ for each regimen, aiming at getting clues as to how to choose OS protocols according to AMH levels. We further addressed how AMH value connects with ART outcome. Methods: A total of 1112 women undergoing egg retrieval in ART were included. We adopted four OS protocols, that is, clomiphene, clomiphene + low‐dose gonadotropins (Gns), GnRH (Gn‐releasing hormone) + Gns (short), and GnRH antagonist. Results: Anti‐Műllerian hormone showed a stronger correlation with egg number compared with age over a wide age range. When patients were stratified into four groups by AMH value (<1, 1‐2, 2‐3, and 3≦ ng/mL), the relationship between AMH and egg number differed among differential OS regimes. The number of eggs rose as AMH and total doses of Gn increased. When analyzed for each AMH group, egg number, but not AMH, was associated with pregnancy rate. Conclusion: Different AMH levels exhibit characteristic responses to distinct OS regimens. To improve ART outcomes, personalized OS should be selected so as to maximize egg number, which seems to be a more precise variable than AMH for predicting pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether supraphysiological estradiol (E2 ) in controlled ovarian stimulation (COS) cycles affects the subsequent frozen-thawed embryo transfer (FET) in terms of the neonatal birthweight.Design: Retrospective cohort study.Setting: University affiliated hospital.Population: In all, 2066 patients undergoing FET cycles that resulted in live singleton births between July 2011 and Dec 2016.Interventions: None.Methods: Multivariable linear regression and logistic regression was used to evaluate the association between peak E2 and birthweight outcomes.Main Outcome Measures: Birthweight, z-score adjusted for gender and gestational age, and incidence of small-for-gestational-age (SGA) and low birthweight (LBW) in singleton neonates derived from FET cycles.Results: Adjusted for confounding factors, both the absolute birthweight and the z-score of singletons following FET were negatively associated with peak E2 levels in COS. In comparison with the referent category (E2  ≤1500 pg/ml), the categories with E2  >3000 pg/ml had a significantly lower z-score. The difference (95% CI) in estimated marginal mean of birthweights between referent category and highest E2 (>8000 pg/ml) category was 104.57 g (18.13-181.06). Multiple logistic regression analyses showed that the adjusted odds ratio (95% CI) for SGA and LBW in term singletons comparing patients with E2  >3000 pg/ml with those with E2  ≤3000 pg/ml was 2.44 (1.37-4.34) and 2.32 (1.01-5.40), respectively.Conclusions: Peak E2 levels in COS cycles are negatively associated with the birthweight of singletons conceived through subsequent FET cycles.Tweetable Abstract: The birthweight following FET is affected by previous COS cycle. [ABSTRACT FROM AUTHOR]

Summary: Objective: The stability of anti‐Müllerian hormone (AMH) across and between menstrual cycles has been the subject of debate. The objective of this analysis was to study the inter‐ and intracycle variability in repeated measurements and assess the impact on an individualized gonadotropin dosing algorithm and predicted oocyte yield. Design: Retrospective analysis of repeat AMH measures from a randomized controlled trial. Patients: A total of 1326 women aged 18‐40 years. Measurements: Serum AMH levels at screening and at cycle day 2‐3 in up to three ovarian stimulation cycles. AMH variability and its impact on gonadotropin dose and the predicted number of oocytes. Results: Repeat serum AMH measurements were strongly correlated within individual women (correlation coefficient 0.92). AMH exhibited limited within‐subject variation (coefficient of variation 23%), a small time‐related decline (mean 6% decrease/y), but no systematic variation across the menstrual cycle. Irrespective of whether the AMH screening value or the AMH at the initiation of ovarian stimulation was used, for women with an AMH level <15 pmol/L, 93% would receive the same gonadotropin dose and attain an identical number of oocytes in 97% of cases. For women with an AMH level ≥15 pmol/L, 80% would receive an individualized dose within ±1.5 μg and 90% would attain ±1 oocyte. Conclusion: AMH variability had limited impact on individualized gonadotropin dosing, with 95% of women predicted to obtain an oocyte yield that does not vary beyond 1 oocyte count, irrespective of whether a random or early follicular AMH measurement was used to determine the individualized gonadotropin dose. [ABSTRACT FROM AUTHOR]

Objective: To compare dual oocyte retrieval with minimal ovarian stimulation and embryo transfer in the same menstrual cycle versus conventional ovarian stimulation among women with premature ovarian insufficiency (POI).Methods: A retrospective study of 51 women with POI attending a reproductive center in Turkey between 2013 and 2015. Women with an ovarian follicle of 12 mm or larger early in the follicular phase who underwent oocyte retrieval followed by an immediate cycle of ovarian stimulation (group 1, n=14) were compared with those who received conventional ovarian stimulation (group 2, n=37). Both groups underwent subsequent ovarian stimulation cycles to obtain optimally two embryos for transfer.Results: The groups had similar baseline parameters. Serum estradiol was higher in group 1 (P<0.001); total number of oocyte retrievals was higher in group 2 (P<0.001); and total number of oocytes retrieved was similar (P=0.192). Group 1 had more higher-quality embryos (P=0.031). There was a non-significant trend toward higher live birth rates in the dual trigger group (28% vs 8%, P=0.08).Conclusion: Rescuing growing follicles early in the follicular phase combined with subsequent ovarian stimulation and embryo transfer in the same cycle resulted in fewer oocyte retrieval cycles and might potentially improve reproductive outcomes. [ABSTRACT FROM AUTHOR]

Background: An ever‐increasing number of women in our country with advanced maternal age are choosing to achieve pregnancy. This means effective strategies are needed for infertile patients. Questions arise, however, concerning the need for ovarian stimulation, and, if so, whether intracytoplasmic sperm injection (ICSI) is better than conventional insemination for those women who may have only one mature oocyte. Methods: We evaluated our data to answer these questions. Herein, we also introduce our strategy for patients who show unsynchronized follicular growth. Main findings: Ovarian stimulation in ART treatment for patients with advanced maternal age has resulted in the achievement of higher pregnancy rates, and therefore, this form of stimulation is often selected. Based on our data, ICSI as an insemination procedure has not improved clinical pregnancy rates compared with conventional insemination and has actually decreased the clinical pregnancy rates. Conclusion: In this article, we reviewed and compared the protocols and strategies that are available to increase the number of developed embryos for the patients with advanced maternal age. We hope that this review will be helpful for both patients and clinicians. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the optimized protocol of low dose follicle‐stimulating hormone (FSH) therapy that has a starting dose of 50 IU/62.5 IU with a small increment dose (12.5 IU) for women with World Health Organization (WHO) II ovulatory disorder and unexplained infertility. Methods: Anovulatory women with WHO group II ovulatory disorder (ovulation induction [OI] patients, n = 29), and with an unexplained infertility (ovarian stimulation [OS] patients, n = 21) were enrolled. The protocol of low dose step‐up FSH therapy was optimized for the starting dose as 50 IU (body mass index [BMI] < 20 group) and 62.5 IU (BMI ≥ 20 group) with the increment dose of 12.5 IU. Study outcomes were ovulation, monofollicular development and other variables. Results: In the OIpatients, the ovulation rate was 100% (BMI < 20 group) and 90.9% (BMI ≥ 20 group). Monofollicular development was 80.0% (BMI < 20) and 77.3% (BMI ≥ 20). The pregnancy rate was 60% (3/5 BMI < 20) and 18.2% (4/22 BMI ≥ 20). There was no multiple pregnancy. In the OSpatients, the ovulation rate was 100%. Monofollicular development was 85.7% (BMI < 20) and 76.6% (BMI ≥ 20). No pregnancy was achieved in the OSpatients. Conclusion: Optimized protocol of low dose FSH therapy setting a starting dose 50 IU/62.5 IU by BMI with an increment dose of 12.5 IU was safe and highly effective in WHO group II anovulatory patients. However, this protocol seemed uneffective for patients with unexplained infertility. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The study assesses the effect of the vitrification procedure on the integrity, morphology, follicular development and gene expression of stimulated human ovarian tissue after warming and two weeks of in vitro culture. Methods: Ovarian specimens were divided into non‐vitrified and vitrified groups and were cultured for two weeks. Morphological analysis and immunohistochemistry were performed. The 17‐β estradiol and anti‐Müllerian hormone levels in collected media were assessed. Gene expression was analyzed using real‐time reverse transcription polymerase chain reaction. Results: The morphology and immunohistochemistry of bcl‐2‐like protein 4 and B‐cell lymphoma 2 of human stimulated ovarian tissue were similar in both groups. There was no significant difference in the percentage of normal follicles between the groups before and after in vitro culture. In spite of an increase in the percentage of growing follicles in cultured tissues compared to the non‐cultured groups, the rate of normal follicles was significantly decreased in both cultured groups (P < 0.05). Gene expression was no different in vitrified tissues compared to the control; however, the expression of growth differentiation factor 9 and follicle stimulating hormone receptor genes were increased and factor in germ line alpha and kit ligand genes were decreased during in vitro culture (P < 0.05). In the two cultured groups, the level of 17‐β estradiol was increased (P < 0.05), but the anti‐Müllerian hormone concentration was not statistically altered. Conclusions: These results showed that the integrity of stimulated human ovarian tissue after vitrification/warming was well preserved; however, the in vitro culture condition needs improvement. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We investigated whether recombinant mouse interleukin‐6 (IL‐6) affects the development of preimplantation embryos and induces the ‐signal transducers and activators of transcription (JAK–STAT) signaling pathway by binding IL‐6 signal transducer (IL‐6st) and regulating Fos and Jun gene expression, thereby accounting for the negative effect of superovulation on embryo development. Methods: We compared rates of blastocyst formation from embryos cultured with different concentrations of IL‐6 or/and anti‐interleukin 6 receptor antibody (anti‐IL‐6RAb) in superovulated experimental and normal control groups. IL‐6 expression in preimplantation embryos was determined by immunofluorescence identification. Fos, Jun and IL‐6st messenger RNA expression was detected by PCR and microarray experiments. Results: Rates of blastocyst formation significantly decreased in superovulated embryos, whether or not they were incubated in 0.1, 1, 25 or 50 pg/mL IL‐6, (P < 0.01) compared to embryos from naturally ovulated controls, whereas incubation in 5 and 10 pg/mL IL‐6 reversed the negative effects of superovulation. The addition of anti‐IL‐6RAb to naturally ovulated embryos reduced blastocyst rates to those of superovulated embryos. Gene chip analysis indicated that the JAK–STAT signaling pathway contained differentially expressed IL‐6, IL‐6st, Jun and Fos genes. Both anti‐IL‐6RAb or ovarian stimulation downregulated IL‐6st, Jun, and Fos messenger RNA expression, but expression of the same three genes increased in 5 pg/mL IL‐6. Conclusion: Ovarian stimulation negatively impacts the development of preimplantation embryos by reducing IL‐6 release. IL‐6 affects the rate of development of zygotes to blastocyst by regulating IL‐6st, Fos and Jun expression in the JAK–STAT signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives To investigate the effects of low-dose human chorionic gonadotropin ( hCG) combined with human menopausal gonadotropin ( HMG) protocol on cycle characteristics and outcomes of infertile women with hypogonadotropic hypogonadism ( HH) undergoing ovarian stimulation for in vitro fertilization ( IVF). Design A retrospective cohort study. Setting Tertiary-care academic medical centre. Patient(s) Forty-six infertile patients with HH and seventy-one infertile patients with tubal factor ( TF) infertility undergoing IVF. Intervention(s) In the study group, all 46 HH patients were given low-dose hCG (50-300 IU/d) in combination with HMG daily from cycle day 3. Meanwhile, a control group consisting of 71 patients with tubal factor infertility was set up, where the infertile women were given triptorelin 3.75 mg on cycle day 3 for desensitization and started stimulation with HMG only 5 weeks later. Transvaginal ultrasound and serum sex steroids were used for monitoring the development of follicles. Ovulation was triggered by hCG 5000 IU when dominant follicles matured. Viable embryos were transferred on the third day after ovum pickup or cryopreserved for later transfer. Main Outcome Measure(s) The primary outcome measure was the clinical pregnancy rate. Secondary outcomes included hCG day P4, ratio of E2/follicle count, number of oocytes retrieved, number of viable embryos, implantation rate, ongoing pregnancy rate and cumulative pregnancy rate. Result(s) With lower basal FSH, LH and E2, HH patients showed longer HMG stimulation duration (13 (10-22) d vs 12 (8-18) d, P < .001) and higher HMG dose (2960 ± 560 IU vs 2663 ± 538 IU, P = .005). Whilst the antral follicle count ( AFC), number of follicles with diameters greater than 10mm on trigger day and oocytes retrieved were less in the HH group, the number of follicles with diameters greater than 14 mm and viable embryos were comparable. The ratio of E2/follicle count (>10 mm) and E2/follicle count (>14 mm) were distinctively higher in the HH group (1056 ± 281 vs 830 ± 245, P < .001; 1545 ± 570 vs 1312 ± 594pmol/L, P = .037; respectively). The clinical pregnancy rate, implantation rate, ongoing pregnancy rate and cumulative pregnancy rate per woman were comparable between the two groups. Comparison among the subgroups with different hCG dosage showed that HMG duration shortened with the increase of daily hCG dose (14.84 ± 2.88 vs 13.96 ± 2.63 vs 12.96 ± 1.30 days, P = .037). No significant differences were detected in outcomes between fresh embryo transfer ( ET) group and frozen-thawed embryo transfer ( FET) group. Conclusion(s) Low-dose hCG combined with HMG is a feasible protocol for HH women undergoing ovarian stimulation in IVF, providing favourable cycle characteristics and pregnancy rates. Low-dose hCG reduces HMG duration, whilst the hCG dose and embryo quality are not positively correlated. The outcomes of FET are comparable to ET, which provides a greater chance of success from IVF in the low responders with HH. [ABSTRACT FROM AUTHOR]

Objective: To assess the available evidence comparing effectiveness of ovarian stimulation (OS) using clomiphene citrate (CC) and/or letrozole (LTZ) to reduce follicle-stimulating hormone (FSH) consumption compared with standard OS.Methods: We performed a systematic review and meta-analysis of randomized controlled trials that compared reproductive outcomes following in-vitro fertilization. We searched 11 electronic databases and hand-searched the reference lists of included studies and related reviews. We stratified the results, separating studies according to the oral agent used (CC or LTZ) and the characteristics of the included women (expected poor ovarian response or other women). When combining the results of the included studies, we assessed the relative risk (RR) for live birth, clinical pregnancy, miscarriage and cycle cancelation, the Peto odds ratio (OR) for ovarian hyperstimulation syndrome (OHSS) and mean difference (MD) for the number of oocytes retrieved and FSH consumption.Results: A total of 22 studies were included in the review. Considering women with expected poor ovarian response, the available evidence suggested that using CC to reduce FSH consumption during OS provided similar rates of live birth (RR, 0.9 (95% CI, 0.6-1.2), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.4), moderate-quality evidence); the use of LTZ did not cause a relevant change in the number of oocytes retrieved (MD, -0.4 (95% CI, -0.9 to 0.1), high-quality evidence). Considering the studies evaluating other women, the available evidence suggested that using CC to reduce FSH consumption during OS reduced the number of oocytes retrieved (MD, -4.6 (95% CI, -6.1 to -3.0), high-quality evidence) and risk of OHSS (Peto OR, 0.2 (95% CI, 0.1-0.3), moderate-quality evidence), while results were similar for rates of live birth (RR, 0.9 (95% CI, 0.7-1.1), moderate-quality evidence) and clinical pregnancy (RR, 1.0 (95% CI, 0.8-1.1), high-quality evidence). The quality of the evidence was low or very low for other outcomes.Conclusion: The use of CC to reduce FSH consumption in women with expected poor ovarian response has the advantage of providing similar reproductive outcomes with reduced costs. For the other women, the use of CC for reducing FSH consumption has the additional advantage of reducing OHSS, but also reduces the total number of oocytes retrieved. More studies are needed to evaluate the effect of LTZ for the same purpose. Future studies should focus on cumulative pregnancy per oocyte retrieval, patient dissatisfaction and agreement to repeat the cycle if not pregnant, which are important outcomes for clinical decisions. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Key Clinical Message Few successful pregnancies after age 45 years with low ovarian reserve have been reported. We report a 46-year-old woman with basal FSH 20.36 mIU/ mL and an antral follicle count of four obtained two embryos and delivered a healthy infant with IVF using a microdose Gn RH-a flare-up protocol combined with Gn RH-ant. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of ovarian stimulation on the outcome of intrauterine insemination (IUI).Design: Retrospective analysis.Setting: A single university-based centre.Population: A total of 5109 couples with 8893 cycles.Methods: The outcome of IUI with different protocols for ovarian stimulation was examined.Main Outcome Measures: The live birth rate (LBR), twin pregnancy rate and ovarian hyperstimulation syndrome (OHSS).Results: In ovulatory women without ovarian stimulation, the LBR was 7.6%. Stimulation with clomifene citrate (CC), letrozole (LE), human menopausal gonadotrophin (HMG), CC or LE combined with HMG achieved LBRs of 6.1, 5, 7.9, 8 and 12.2%, respectively. LE combined with HMG achieved a significantly improved LBR compared with no stimulation. HMG stimulation was associated with a higher rate of twins (7.4%) than no stimulation (0%, P < 0.01). In ovulatory women, the LBR appeared lower in CC and LE compared with no stimulation (P > 0.05). In anovulatory women, ovarian stimulation with CC, LE, HMG, CC or LE combined with HMG achieved LBRs of 11.3, 5.1, 11.8, 12.6 and 13.6%, respectively. No significant difference was observed. There were no triplet pregnancies or OHSS in stimulated cycles.Conclusions: In ovulatory women, ovarian stimulation with LE combined with HMG achieved a significantly improved live birth rate. HMG stimulation resulted in a high risk for twins.Tweetable Abstract: In ovulatory women, ovarian stimulation with letrozole and HMG resulted in a significantly improved LBR. [ABSTRACT FROM AUTHOR]

OBJECTIVE To quantify the risk of major congenital malformations (MCMs) associated with the use of ovarian stimulators alone, intrauterine insemination (IUI), and assisted reproductive technologies (ARTs). METHODS We conducted a case-control analysis using a birth cohort, built with the linkage of data obtained by a self-administered questionnaire, medical, pharmaceutic, and birth databases. Cases were pregnancies with at least one live birth with an MCM. Controls were pregnancies that did not result in major or minor congenital malformations. Multiple logistic regression models were used to calculate the odds ratios (ORs) and confidence intervals (CIs). RESULTS Among the 5021 pregnancies identified, 825 were cases of MCM and 4196 were controls. Compared with spontaneous conception, the use of ART increased the risk of major urogenital malformations (adjusted OR, 3.11; 95% CI, 1.33-7.27). The use of IUI was associated with an increased risk of major musculoskeletal malformations (adjusted OR, 2.02; 95% CI, 1.10-3.71). Among the 471 women who used fertility treatments for conception, the use of ART was associated with an increased risk of any MCM (adjusted OR, 1.66; 95% CI, 1.00-2.79) and urogenital malformations (adjusted OR, 7.18; 95% CI, 1.59-32.53) when compared with ovarian stimulators used alone. CONCLUSIONS The use of ART and IUI was associated with an increased risk of major musculoskeletal and urogenital malformations. ART was associated with a higher risk of MCM compared to ovarian stimulators used alone. Even the adjustment, a contribution of the underlying subfertility problems cannot completely ruled out given the differences in the severity of subfertility [ABSTRACT FROM AUTHOR]

Objective: To compare cumulative live birth rate according to the rate of use of metaphase II (MII) oocytes in conventional ovarian stimulation protocols for in vitro fertilization (IVF) or intracytoplasmic sperm injection.Methods: In a cohort study, patients aged 18-38 years undergoing their first IVF treatment at one US center were enrolled between February 1, 2009, and August 31, 2013. Ovarian response was categorized by the yield of MII oocytes (low: 1-2; intermediate: 3-6; high: ≥7). The main outcome measure was cumulative live birth rate over a 6-month period.Results: Among 250 participants, 3240 oocytes (mean±SEM 12.96±0.50) were retrieved and there were 152 (60.8%) live births. Overall, 172 (68.8%) participants had a high oocyte yield, 61 (24.4%) an intermediate yield, and 17 (6.8%) a low yield. The cumulative live birth rate was 58.8% (10/17) in the low-yield group, 55.7% (34/61) in the intermediate-yield group, and 62.8% (108/172) in the high-yield group (P=0.35).Conclusion: In conventional ovarian stimulation, live birth rate is not affected by the ovarian response. Whether oocytes produced from a low ovarian response are biologically more effective than oocytes obtained from a high ovarian response remains to be determined. [ABSTRACT FROM AUTHOR]

Intrauterine insemination ( IUI) is an effective, noninvasive, relatively simple and cheap method of infertility treatment. Many factors that affect IUI outcomes have been studied. However, there is no consensus about the optimal number of motile spermatozoa inseminated ( NMSI) required for a reasonable chance of pregnancy after IUI. In this retrospective study, we aimed to assess the relationship between NMSI and the pregnancy rate after IUI with husband's spermatozoa. Couples who had either primary or secondary infertility for more than one year were recruited from the Department of Reproduction, Nanjing Maternity and Child Health Hospital, China, between January 2007 and December 2010. Overall, 1153 IUI cycles with husband's spermatozoa were performed in 645 women after ovarian stimulation. Factors that have previously been associated with a successful fertilisation after IUI were assessed. A total pregnancy rate of 13.88% was obtained. The pregnancy rate was only 4.05% if less than 2 × 106 motile spermatozoa were used, but this rose to 14.55% when more than 2 × 106 motile spermatozoa were inseminated. We therefore conclude that IUI can be performed when the NMSI exceeds 2 × 106. With this recommendation, IUI with husband's spermatozoa can be used to treat many more infertile couples. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to examine the effects of estradiol valerate ( EV) on the thickness of clomiphene citrate ( CC)-stimulated endometrium. Material and Methods Thirty-four normal ovulatory women were randomized double-blindly into two groups to receive CC 100 mg/day on day 2-6 of the treatment cycle, and either vitamin B (placebo) or EV 6 mg/day on day 10-14 of the cycle. The endometrial thickness, endometrial pattern, numbers of mature follicles, and maximal diameters of preovulatory follicles were evaluated by transvaginal sonographic examination. Results Thirty women completed both treatment cycles. Two other participants dropped out during the treatment due to side-effects (headache). The average endometrial thickness of the group treated with CC + placebo became slightly thinner when compared to the thickness at the baseline (9.04 vs 9.52 mm; P = 0.24). The CC + placebo and the CC + EV resulted in similar endometrial pattern, ovulation day, numbers of mature follicles, and sizes of the leading follicles before ovulation. However, an addition of EV into the CC cycle significantly increased the average endometrial thickness (10.7 mm vs 9.04 mm; P < 0.001). Conclusions We concluded that the addition of 6 mg/day EV following the CC treatment can prevent the endometrial thinning without perturbing folliculogenesis and ovulation. [ABSTRACT FROM AUTHOR]

Synopsis: The administration of growth hormone during ovarian stimulation in women with RIF and PCOS may improve intracytoplasmic sperm injection outcomes. [ABSTRACT FROM AUTHOR]

Objective. To assess the psychological impact (Hospital Anxiety and Depression Scale) of an investigational ovarian stimulation protocol in women with premature ovarian failure (POF). Design. Prospective longitudinal study. Population. Ten women with POF. Methods. Women with idiopathic POF were placed on three consecutive treatment cycles consisting of gonadotropin ovarian stimulation after estrogen priming, gonadotropin-releasing hormone agonist pituitary desensitization, and corticosteroid immune suppression. Results. Median anxiety and depression scores increased significantly from baseline following three consecutive treatment cycles from 4.0 (range 2.0-8.0) to 11.0 (range 10.0-14.0) ( p-value 0.041) and from 1.5 (range 0-6.0) to 9.0 (range 7.0-10.0) ( p-value 0.039), respectively. There were nine 'probable' anxiety (90%) and three 'probable' depression (30%) cases on the final treatment cycle compared with none (0%) on baseline ( p-value 0.004 and 0.250, respectively). Conclusions. The use of investigational ovarian stimulation protocols in women with idiopathic POF was associated with excessive psychological strain. Women with POF should be cautioned against the potentially harmful aspect of similar treatments of unproven benefit. [ABSTRACT FROM AUTHOR]

Problem In our previous study, ovarian stimulation retarded post-implantation development and caused 92 genes, including interleukin-6 ( IL-6), to be differentially expressed in mouse blastocysts. None of them had been tested at protein level, In this study, we confirm the level change of IL-6 m RNA in mouse blastocysts and IL-6 protein release to the culture medium from mouse and human pre-implantation embryos. Method of study IL-6 mRNA were measured by PCR and IL-6 release to the culture medium were measured by ELISA. Results Superovulation caused a 1.95-fold reduction in IL-6 m RNA in mouse blastocysts and reduced IL-6 secretion into the culture medium in mouse zygotes which were developed to the blastocyst stage (6.397 ± 0.635 versus 4.799 ± 0.312 pg/mL). Ovarian stimulation also significantly reduced IL-6 release into the culture medium in human zygotes which were cultured for 2 days (4.713 ± 0.945 versus 4.543 ± 0.796 pg/mL). Conclusion Our findings indicate that IL-6 might serve as a candidate marker for evaluating embryo developmental competence. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effect of supplementation with recombinant human luteinizing hormone (rhLH) for patients treated either with recombinant follicle stimulating hormone (rFSH) plus rhLH or with rFSH plus human menopausal gonadotrophin (HMG) in a long gonadotrophin-releasing hormone (GnRH) agonist-stimulation protocol. Methods: A single-centre, retrospective analysis of patients with hypo responsiveness to a long GnRH agonist protocol ( n = 174), with consecutive in-vitro fertilization or intracytoplasmic sperm injection cycles, compared the outcomes of long luteal GnRH agonist ovarian stimulation using rFSH combined with HMG ( n = 100) versus rFSH combined with rhLH ( n = 74). The endpoints included clinical pregnancy, number of oocytes retrieved, and total gonadotrophin dose. Results: Significantly more clinical pregnancies were achieved after stimulation with rFSH and rhLH than after stimulation with rFSH and HMG (35.1 vs. 19%, p < 0.01). More oocytes were recovered (13.1 vs. 11.3, p = 0.024) with less FSH utilized in the rFSH and rhLH group than in the rFSH and HMG group (2706.4 vs. 4134.2 U, p < 0.001). Conclusions: Use of rFSH combined with rhLH in long GnRH agonist assisted reproductive technology (ART) cycles was associated with more clinical pregnancies, recovery of more oocytes, and reduction in gonadotrophin use, suggesting that the superior purity and consistency of rFSH and rhLH may result in better clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management. Outcomes: These guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes. Evidence: Medline, Embase, and the Cochrane database were searched for relevant articles, using the key words “ovarian hyperstimulation syndrome” and “gonadotropins,” and guidelines created by other professional societies were reviewed. Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). [Copyright &y& Elsevier]

Junovich G, Mayer Y, Azpiroz A, Daher S, Iglesias A, Zylverstein C, Gentile T, Pasqualini S, Markert UR, Gutiérrez G. Ovarian stimulation affects the levels of regulatory endometrial NK cells and angiogenic cytokine VEGF. Am J Reprod Immunol 2011; 65: 146-153 Endometrial NK cells play a critical role in uterine vascularization producing angiogenic factors. Impact of ovarian stimulation on endometrial expression of NK cells and VEGF in normal fertile oocyte donors and the effect of endometrial injury treatment on these parameters have been investigated. Endometrial tissue was obtained from oocyte donors during natural and stimulated cycles. NK cell subsets were measured by flow cytometry. VEGF was determined by ELISA and flow cytometry. Endometrial angiogenic parameters were determined by ultrasound Doppler. Local injury was induced by scratching endometrial tissue previous to implantation window. Ovarian stimulation decreased endometrial levels of NK cells and vascularization index but increased VEGF levels. Local injury normalized only the CD56 NK cell count. Hormonal therapy for ovarian stimulation may be associated with poor endometrial vascularization. Local injury before the implantation window seems not to influence endometrial angiogenic parameters altered by ovarian stimulation. [ABSTRACT FROM AUTHOR]

Poor ovarian response is not infrequent and represents one of the major therapeutic challenges in in vitro fertilization. Although several tests have been proposed, which aim at predicting poor response to ovarian stimulation, available data are conflicting regarding their accuracy and clinical usefulness. Even though several therapeutic approaches have been explored, a single effective strategy has not yet been established. One of the major limitations of interpreting the relevant literature is the wide variability in the definitions used for poor ovarian response. Regarding the interventions that have been proposed to improve the probability of pregnancy in poor responders, limited evidence from relevant randomized controlled trials suggests that addition of growth hormone during ovarian stimulation, as well as performing embryo transfer on day 2 instead of day 3, might be beneficial. Further randomized control trials are warranted to reliably determine which would be the best approach for treating poor ovarian response. [ABSTRACT FROM AUTHOR]

To simplify the procedure for superovulation in the rhesus monkey, this study was designed using polyvinylpyrrolidone (PVP) solution as a solvent for gonadotropins. Thirty-five cycling females (aged 5–8 years old) were divided into six groups during the breeding season (November– February). The groups were as follows: Group I, animals received twice-daily 35 IU recombinant human follicle-stimulating hormone (rhFSH) dissolved in 0.5 ml saline for 8 days as the control; Groups II and III, animals received single-daily 35 IU and 17 IU rhFSH in 0.5 saline, respectively, for 9 days; Groups IV, V and VI, received single-daily injection of 35 IU rhFSH, 17 IU rhFSH and 8.5 IU rhFSH dissolved in 0.5 ml 30% PVP (w/v) solution, respectively, for 9 days. After human chorionic gonadotropin was administered to induce the nuclear maturation of oocytes, oocytes were retrieved and the development competence of recovered oocytes treated with in vitro fertilization were observed. The plasma concentrations of follicle-stimulating hormone and ovarian responses were monitored during the treatment. The results showed that the number of recovered oocytes and the in vitro developmental competence of mature oocytes was equivalent among monkeys when treated with a single-daily treatment of 17 and 35 IU rhFSH with PVP preparation in Groups IV and V compared with the twice-daily 35 IU rhFSH treatments received by Group I. However, almost all animals in Groups II, III and VI responded poorly to corresponding stimulations. These findings indicate that a single-daily low dose of rhFSH dissolved in PVP solution can induce the satisfactory ovarian responses in rhesus monkeys. This has the potential to reduce treatment distress, stress to the animals, the labor of the operator as well as the amount of rhFSH used in ovarian stimulation, compared with traditional superovulation methods. Am. J. Primatol. 69:1278–1284, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The vervet monkey was evaluated as a primate model for use in assisted reproductive technologies (ARTs). Eight adult female vervets were hormonally monitored for their potential use as egg donors and those six females displaying regular menstrual cycles were subjected to controlled ovarian stimulation with recombinant human gonadotropins. Three animals failed to respond while laparoscopic follicular aspiration was performed on the other three females at 27–30 h post-human chorionic gonadotropin administration. A total of 62, 40, and 18 oocytes was recovered from these three animals of which 30, 20, and 4, respectively, matured to the metaphase II stage and were subsequently inseminated using intracytoplasmic sperm injection. An average of 40±15% (SEM) of the inseminated oocytes were fertilized based on pronucleus formation and timely cleavage. One embryo from each of the two stimulated females developed into expanded blastocysts. Two adult male vervets were assessed as sperm donors. Neither adjusted well to the restraint and collection procedure required for penile electroejaculation. Samples collected via rectal electroejaculation were very low in sperm motility and concentration; however, cauda epididymal aspirations from one male yielded an adequate concentration of motile sperm. These results emphasize the need to establish species-specific ovarian stimulation protocols and semen collection techniques if vervets are to be considered for basic and applied (ARTs) research on primate gametes or embryos. Am. J. Primatol. 69:917–929, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to identify the risk factors, their prognostic value on multiple pregnancies (MP) prediction and their thresholds in women undergoing controlled ovarian hyperstimulation (COH) with follicle stimulating hormone (FSH) and intrauterine insemination (IUI). Methods: A case-control study was carried out by identifying in our database all the pregnancies reached by donor and conjugal IUI (DIUI and CIUI, respectively), and compared cycle features, patients’ characteristics and sperm analysis results between women achieving single pregnancy (SP) versus MP. The number of gestational sacs, follicular sizes and estradiol levels on the human chorionic gonadotropin (hCG) administration day, COH length and semen parameters were obtained from each cycle and compared. Student's t-tests for mean comparisons, receiver–operator curve (ROC) analysis to determine the predictive value of each parameter on MP achievement and multiple regression analysis to determine single parameter influence were carried out. Results: Women with MP in IUI stimulated cycles reached the adequate size of the dominant follicle (17 mm) significantly earlier than those achieving SP. Also, the mean follicles number, and estradiol levels on the hCG day were higher in the CIUI and DIUI MP group. Nevertheless, only ROC curve analysis revealed good prognostic value for estradiol and follicles higher than 17 mm. Multiple regression analysis confirmed these results. No feature of the basic sperm analysis, either in the ejaculate or in the prepared sample, was different or predictive of MP. When using donor sperm, different thresholds of follicle number, stimulation length and estradiol in the prediction of MP were noted, in comparison with CIUI. Conclusions: MP in stimulated IUI cycles are closely associated to stimulation length, number of developed follicles higher than 17 mm on the day of hCG administration and estradiol levels. Also, estradiol has a good predictive value over MP in IUI stimulated cycles. The establishment of clinical thresholds will certainly help in the management of these couples to avoid undesired multiple pregnancies by canceling cycles or converting them into in vitro fertilization procedures. (Reprod Med Biol 2007; 6: 19–26) [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to establish a standard protocol for ovarian stimulation with gonadotropin-releasing hormone analog (GnRH-a) long protocol using recombinant-follicle stimulating hormone (rec-FSH) preparations for assisted reproductive technology (ART) treatment. Methods: In 86 patients who underwent ovarian stimulation with GnRH-a long protocol for ART treatment, 53 were stimulated by rec-FSH preparations (rec-FSH group) and the others were stimulated by urinary-hMG (u-hMG group) preparations. The subjects were randomly assigned to either of these preparations. Hormonal profiles, total doses of gonadotropins, duration of stimulation and ART results were compared in both groups. Results: The duration of stimulation was similar in both groups (9.2 ± 0.3 days and 9.2 ± 0.2 days, respectively). The total doses of gonadotropin in the rec-FSH group (1505.3 ± 29.2 IU) was significantly lower than those in the u-hMG group (2130.3 ± 54.6 IU, P < 0.0001). The FSH and LH values on the day of human chorionic gonadotropin (hCG) administration in the rec-FSH group were significantly lower than those in the u-hMG group. Pregnancy rates were 31.3% in the rec-FSH group and 33.3% in the u-hMG group, respectively. Conclusions: The present study showed that rec-FSH preparations were more potent than conventional u-hMG preparations and the protocol of the present study with rec-FSH was a new ovarian stimulation protocol with GnRH-a long protocol. (Reprod Med Biol 2007; 6: 27–32) [ABSTRACT FROM AUTHOR]

Management of women with a poor response to controlled ovarian hyperstimulation during IVF remains a frustrating challenge. The present study included 96 cycles from an equal number of women with a poor ovarian response and successful oocyte retrieval. Poor response was defined by the presence of at least one of the following characteristics: three or fewer oocytes on retrieval, serum estradiol level less than 500 pg/mL on the day of hCG administration, and serum FSH levels less than 20 IU/L. The same patients had a previous cycle cancelled because of a poor ovarian response whereas in the second cycle they preferred to continue the treatment despite the poor prognosis. We obtained 241 oocytes in the 96 IVF cycles. The fertilization rate was 60.2%. Three oocytes per cycle were retrieved in 56 cycles (58.3%), two oocytes per cycle in 33 cycles (34.4%), and one oocyte per cycle in 7 cycles (7.3%). In 19 cycles (19.8%) no fertilization was achieved. An embryo transfer was finally performed in 74 out of 96 cycles. Pregnancy rate was 12.5% per cycle and 16.2% per transfer. Among the 12 pregnancies achieved, 7 were in the 3-oocyte cycles and 5 in the 2-oocyte cycles. No pregnancies were achieved in the 1-oocyte cycles. Our data demonstrate that continuation of therapy in poor responders undergoing IVF can be an option despite the low pregnancy rates. The prognosis of these patients is not affected by a poor response in the first cycle and for some of them the outcome can be favorable. [ABSTRACT FROM AUTHOR]

Aim: To determine whether minimal stimulation with clomiphene and gonadotropin provides outcomes and direct costs comparable with those of a conventional GnRHa-gonadotropin stimulation protocol for infertile patients undergoing in vitro fertilization. Methods: A non-randomized clinical trial was conducted from 1 July 1996 to 31 March 2003 at the Infertility and Assisted Reproductive Unit, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Thailand. A total of 192 patients were recruited of whom 96 cases underwent ovarian stimulated cycles with minimal stimulation protocol, and 96 controls underwent ovarian stimulated cycles with GnRHa-gonadotropin protocol, with cases and controls matched for age and infertility cause. Results: The median patient age was 35 years. Endometriosis was the most frequent infertility cause (28.1%). The conventional GnRHa-gonadotropin protocol could give more oocyte numbers than the minimal stimulation protocol (7.3 ± 4.9 vs 4.5 ± 3.3 oocytes). The fertilization rate and cleavage rate were similar (73.4 ± 31.9 and 84.9 ± 32.6 in minimal stimulation protocol, 69.3 ± 29.6 and 88.4 ± 28.0 in GnRHa-gonadotropin protocol, respectively). The pregnancy rate per oocyte retrieval cycle in the GnRHa-gonadotropin protocol was similar to the minimal stimulation protocol. (13.1% vs 13.0%, P = 1.000). However, the cost per pregnancy of minimal stimulation protocol was less than that of GnRHa-gonadotropin protocol. ($US 6021.95 for minimal stimulation protocol per pregnancy, $US 10 785.65 for GnRHa-gonadotropin protocol per pregnancy, P < 0.000). Conclusion: Minimal stimulation was less effective than conventional GnRHa-gonadotropin on the ovarian stimulation. However, the total costs of minimal stimulation were cheaper than the conventional GnRHa-gonadotropin protocol. The decreased costs of minimal stimulation justifies further evaluation of its role in the treatment of infertility in selected cases. [ABSTRACT FROM AUTHOR]

Superovulation by injection of exogenous gonadotropin is the elementary method to produce in vivo-derived embryos for embryo transfer in women. Increased oocyte aneuploidy, embryo mortality, fetal growth retardation, and congenital abnormalities have been studied at higher-dose stimulations. Ovarian and oocyte biological aging possibly may have adverse implications for human oocyte competence with repeated hyperstimulation. In this study, we found that reduced competence for the human oocyte has been associated with degenerative embryo upsurge during embryo culture and failure to develop into the blastocyst stage in the three, four, five, and six stimulation cycles. On the other hand, the numbers of ovulated oocytes were decreased in the groups with more ovarian stimulation. More aggregated mitochondria were found in the cytoplasm of the repetitively stimulated embryos. Higher amounts of oxidative damage including 8-OH-dG, lipoperoxides, and carbonyl proteins were also revealed in the ovaries with more cycle numbers of ovarian stimulation. Higher proportions of mtDNA mutations were also found. The detected molecular size of the mutated band was approximately 675 bp. Increased amounts of carbonyl proteins were also revealed after repeated stimulation. An understanding of the relationship between oocyte competence and ovarian responses to stimulation in the mouse may provide insights into the origin of oocyte defects and the biology of ooplasmic aging that could be of clinical relevance in the diagnosis and treatment of human infertility. [ABSTRACT FROM AUTHOR]

The use of gonadotropin-releasing hormone (GnRH) agonists in a long protocol appears to enhance the probability of conception in the presence of endometriosis. In addition, there is evidence to suggest that the use of prolonged downregulation with GnRH agonists prior to ovarian stimulation for in vitro fertilization (IVF) is beneficial for achieving pregnancy. Until now, GnRH antagonists have not been used in patients with endometriosis. The management of endometriomas prior to stimulation for IVF and its impact on reproductive outcome are still subject to debate. [ABSTRACT FROM AUTHOR]

Background: Women with a single ovary form a group of special interest in assisted reproduction. The aim of this study was to compare the outcome of intracytoplasmic sperm injection cycles between women with one and two ovaries. To our knowledge, this is the first study reporting the outcome of intracytoplasmic sperm injection cycles with women with a single ovary.Methods: Sixty-three intracytoplasmic sperm injection cycles in 24 women with a single ovary were compared with 191 intracytoplasmic sperm injection cycles in 109 women with both ovaries. All cycles were stimulated with triptorelin-long protocol.Results: Statistically significant differences were found in the following parameters between women with a single ovary and women with two ovaries: total number of administrated gonadotropins (63.22 +/- 45.03 vs. 44.72 +/- 21.92), number of follicles (8.29 +/- 5.02 vs. 14.45 +/- 7.94), estradiol peak levels (1695.05 +/- 1177.34 vs. 2728.51 +/- 1852.67), number of retrieved metaphase II oocytes (6.95 +/- 3.78 vs. 11.72 +/- 6.11) and number of 2 PN oocytes (4.07 +/- 2.85 vs. 6.53 +/- 4.14). There were no differences in duration of stimulation, number of transferred embryos, and cumulative embryo score. In the group of women with a single ovary 14 pregnancies were achieved (22.2%), whereas 33 pregnancies were achieved in the group of women with two ovaries (17.28%).Conclusions: Women with a single ovary have a decreased response to external ovarian stimulation than women with both ovaries, but they present a higher, although not statistically significant, pregnancy rate. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective To evaluate arterial and venous intraovarian blood flow in follicle stimulating hormone-stimulated cycles. Subjects and methods This was a prospective study of 76 follicle stimulating hormone-stimulated cycles carried out in 39 infertile patients who were included in a timed intercourse or intrauterine insemination program in a referral center for assisted reproduction. Transvaginal color and pulsed Doppler measurements of the follicular and luteal phase resistance index, pulsatility index, peak systolic velocity and maximum venous velocity were made and serum progesterone levels during the mid-luteal phase were recorded. Velocimetric parameters were established and then used to classify ovarian function as having a normal ovulatory cycle, or a cycle in which there was either luteal phase deficiency or a luteinized unruptured follicle. Results In 52 normal ovulatory cycles, the luteal phase peak systolic and maximum venous velocities were significantly higher and resistance and pulsatility indices were significantly lower than those found in the follicular phase. In 15 women with luteal phase deficiency we did not find any differences in arterial velocimetric parameters when compared with normal ovulatory cycles. However, luteal phase maximum venous velocities were lower in the luteal phase deficiency cycles and there was a significant correlation between luteal phase maximum venous velocity and serum progesterone levels (r = 0.36). Luteinized unruptured follicle cycles (n= 9) did not show significant changes during the ovarian cycle and no ‘luteal conversion’ of the Doppler signal was identified. Conclusions Follicle stimulating hormone-stimulated cycles in infertile patients can have a high percentage of abnormal functional responses that can be diagnosed only by sonographic assessment, Doppler and the appropriate hormonal follow-up. Arterial and venous intraovarian blood flow remain unaltered during luteinized unruptured follicle cycles and serum progesterone levels correlated with luteal phase maximum venous velocity, which makes Doppler a potentially useful non-invasive test to assess ovulation and luteal function. [ABSTRACT FROM AUTHOR]