Controlled Ovarian Hyperstimulation Outcomes Research Articles

Influence of breast cancer prognostic factors on ovarian reserve and response to ovarian stimulation in fertility preservation

Research questionDo breast cancer (BC) prognostic factors influence ovarian reserve and response to controlled ovarian hyperstimulation (COH) in the context of fertility preservation (FP)? DesignObservational, bicentric retrospective study including all BC patients who had vitrified oocytes after COH using a random start GnRH antagonist protocol after measurement of serum AMH levels and antral follicle count (AFC) between November 2015 and August 2022. Three-hundred-fifty-two BC patients having undergone one cycle of COH were analyzed. Number of oocytes recovered (OOR), maturation rate (number of mature oocytes/number of oocytes recovered), and Follicular Output Rate (FORT) were studied according to the patients’ general characteristics, ovarian reserve markers, as well as BC diagnostic and prognostic factors: histological type, uni/multifocal character, TNM or UICC stage, hormonal receptors expression, HER2 status, Ki67, Grade, presence of vascular emboli, lymph node. ResultsOverall, mean patients’ age was 33.6 ± 4.1 years. Mean AFC and serum AMH level were 20.5 ± 13.0 follicles and 2.7 ± 4.6 ng/mL, respectively. After ovarian stimulation, 12.5 ± 8.5 oocytes were recovered and 9.3 ± 6.9 were mature and further vitrified. Mean oocyte maturation rate was 74 ± 23%. Patient's age was significantly related to the number of mature oocytes recovered: the risk of yielding less than 8 oocytes increased significantly after the age of 35 years. Follicular responsiveness to FSH, assessed by the follicular output rate (FORT index) as well as OOR were 30 ± 24% and 12.5 ± 8.5%, respectively. FORT index was not influenced by tumor characteristics and COH outcome was not influenced by breast cancer prognostic factors. ConclusionOur findings indicate that BC prognostic factors do not influence ovarian reserve markers nor the response to ovarian stimulation in the context of FP. Therefore, tumor grade, triple-negative status, overexpression of HER2, and high Ki67 should not modify the FP strategy when COH for oocyte vitrification is considered.

Thyroid-stimulating hormone levels are associated with estradiol levels and impact reproductive outcomes in preconceptionally euthyroid women undergoing their first IVF/ICSI cycles.

Controlled ovarian hyperstimulation (COH) has been reported to affect thyroid function; however, the impact of thyroid-stimulating hormone (TSH) levels during COH on embryo development and early reproductive outcomes has largely not been determined. Therefore, the aim of the present study was to investigate whether TSH levels are associated with COH and impact early reproductive outcomes in preconceptionally euthyroid women. This was a prospective cohort study. A total of 338 euthyroid women who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment using the gonadotropin releasing hormone agonist (GnRH-a) protocol were included. Samples were collected at different representative time points for TSH and estradiol measurements. TSH levels significantly increased with the administration of Gn and maintained this tendency until the trigger day. Basal TSH levels increased along with basal estradiol levels and remained stable when estradiol levels were higher than 150 pmol/L. On the trigger day, TSH levels changed with increasing estradiol levels in the high-normal basal TSH group but not in the low TSH group. TSH did not impact clinical pregnancy or early pregnancy loss after adjusting for age, stage or number of embryos. Serum TSH levels change significantly during COH and are associated with significant changes in estradiol levels. However, euthyroid women with high-normal TSH levels showed similar development potential for inseminated embryos and early reproductive outcomes compared to those with low TSH levels.

Luteinizing Hormone/Human Chorionic Gonadotropin Receptor N312S Single-Nucleotide Polymorphism and Its Impact on Clinical and Reproductive Outcomes in Assisted Reproductive Technology: A Prospective Cohort Study.

Objective The aim of this study was to determine the genotypic distribution of luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) N312S single-nucleotide polymorphism (SNP) and to investigate its impact on clinical and reproductive outcomes in infertile Indian women undergoing assisted reproductive technology (ART). Study design and settings This was a prospective cohort study conducted at a tertiary care university hospital. Subjects and methods Infertile women aged between 21 and 40 years undergoing ART with an antagonist protocol were enrolled in this study. A 2-ml sample of peripheral venous blood was collected from each woman and genotyped for the LHCGR N312S SNP. Participants were divided into three groups based on their SNP: NN, NS, and SS. All subjects underwent controlled ovarian hyperstimulation (COH) through a gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). Of the 140 women recruited based on selection criteria, 128 underwent embryo transfer. We compared the genotypic distribution of the LHCGR N312S SNP, baseline characteristics, clinical outcomes, and reproductive outcomes in ART among the three groups. Data were analyzed using IBM SPSS Statistics for Windows, Version 29 (Released 2022; IBM Corp., Armonk, New York, United States). The chi-square test and Fisher-Irwin test were employed to evaluate significant differences among the qualitative categorical variables. A p-value of less than 0.05 was considered statistically significant. Results Among the test subjects, 19.3% were homozygous for the LHCGR N312 SNP (NN group), 38.6% were heterozygous (NS group), and 42.1% were homozygous for the LHCGR S312 SNP (SS group). Baseline characteristics were similar among the three groups. In terms of ovarian reserve tests, significantly lower anti-Müllerian hormone (AMH) levels were observed in the SS group compared to the NS and NN groups (2.8 ± 2.1 vs. 3.2 ± 2.5 vs. 4.3 ± 3.3; p=0.03). No significant differences were observed in COH outcomes such as duration of stimulation, total gonadotropin requirement, oocyte yield, or the number of good-quality embryos among the three groups. The cumulative pregnancy rate (82.9% vs. 50.0% vs. 38.2%, p=0.0005), cumulative clinical pregnancy rate (78.8% vs. 44.7% vs. 34.5%, p = 0.0005), and cumulative live birth rate (50.0% vs. 20.2% vs. 20.0%, p=0.005) were significantly higher in the NN group than in the NS and SS groups. Conclusion The study's findings suggest that LHCGR N312 may help predict reproductive outcomes in ART, which may aid in providing better counseling to infertile couples. We need more studies on individualized/personalized COH using pharmacogenomics for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) supplementation based on combined FSH and LH receptor SNP and to assess their effects on ART outcomes.

The effect of luteinizing hormone changes in GnRH antagonist protocol on the outcome of controlled ovarian hyperstimulation and embryo transfer

BackgroudTo investigate the effect of Luteinizing hormone (LH) level changes on the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer (ET) in gonadotropin-releasing hormone antagonist (GnRH-ant) protocol.MethodsA total of 721 patients undergoing GnRH-ant protocol COH for the first IVF/ICSI cycles were retrospectively analyzed. COH process were divided into 2 stages, before (stage 1) and after (stage 2) the GnRH-ant initiation, and each with 5 groups basing on LH levels: LH decreased more than 50% (groups A1, A2), decreased 25-50% (groups B1, B2), change less than 25% (groups C1, C2), increased 25-50% (groups D1, D2), and increased more than 50% (groups E1, E2).ResultsThere were no significant differences among groups of stage1 regarding COH and ET outcomes. For stage 2, the more obvious the decrease of LH level, the more the number of oocytes retrieved, mature oocytes, fertilized oocytes, embryos cleavaged and the numbers of embryo available (P < 0.05), but without significant differences regarding ET outcomes. We also found the freeze-all rate in Group A2 was higher (P < 0.001).ConclusionLH level changes before GnRH-ant addition were not related to COH and ET outcomes. LH level changes after the addition of GnRH-ant were related to the outcome of COH, and no significant differences were found relating to ET outcomes.

Response to Ovarian Stimulation for Urgent Fertility Preservation before Gonadotoxic Treatment in BRCA-Pathogenic-Variant-Positive Breast Cancer Patients.

BRCA 1/2 pathogenic variants increase the risk of developing early and aggressive breast cancers (BC). For these patients, fertility potential can be directly affected by oncologic treatments. In addition, evidence indicates that BRCA-mutated women had a significant reduction in their ovarian reserve. In order to improve their chances of conception after the completion of cancer treatments, fertility preservation should be proposed before the administration of gonadotoxic drugs, ideally by oocyte vitrification after controlled ovarian hyperstimulation (COH). The present investigation aims to assess the ovarian response to COH in BRCA 1/2-pathogenic-variant carriers diagnosed with BC. Patient characteristics and COH outcomes were compared between BRCA-positive (n = 54) and BRCA-negative (n = 254) patients. The number of oocytes recovered did not differ between the two groups. However, the oocyte maturation rate and the number of mature oocytes obtained (7 (4.5-11.5) vs. 9 (5-14) oocytes, p = 0.05) were significantly lower in the BRCA-mutated patients. Although individualized COH protocols should be discussed, BRCA-mutated patients would benefit from FP before BC occurs, in order to cope with the potential accelerated decline of their ovarian reserve, optimize the success rate of FP by repeating COH cycles, and to preserve the feasibility of PGT-M by collecting a large amount of eggs.

Early administration of gonadotropin-releasing hormone antagonist versus flexible antagonist ovarian stimulation protocol in poor responders: a randomized clinical trial

BackgroundDetermining the initiation day of antagonist administration is an important and challenging issue and different results have been reported in the previous studies. The present study was designed to compare the controlled ovarian hyperstimulation (COH) cycles outcomes of early-onset gonadotropin-releasing hormone antagonist (GnRH-ant) protocol with conventional flexible GnRH-ant protocol in patients with poor ovarian response (POR) diagnosis. This randomized clinical trial was performed on infertile women who were diagnosed as poor responders in in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles at Arash Women’s Hospital affiliated to Tehran University of Medical Sciences. POR was defined according to the Bologna criteria and the eligible women were randomly allocated into an experimental (early-onset GnRH-ant) and control (conventional flexible GnRH-ant) groups. The women in the experimental group received recombinant gonadotropins (150–225 IU) and GnRH-ant (0.25 mg) simultaneously on the second day of the cycle. In the control group, the starting and the dose of gonadotropins were similar but daily administration of GnRH-ant was initiated when the leading follicle diameter was ≥ 13 mm. The COH outcomes were compared between groups (n=58 in each group).ResultsThe analysis showed that the two groups did not have statistically significant differences in terms of the ovarian stimulation duration and the total dose of used gonadotropins. The total number of metaphase II (MII) oocytes in the experimental group was significantly higher than that of in control group (P = 0.04). Moreover, clinical and ongoing pregnancy rates per embryo transfer (ET) in the experimental group were significantly higher than those in the control group (P = 0.02 and P = 0.03, respectively); however, the implantation and miscarriage rates were similar between groups.ConclusionsThe early-onset GnRH-ant protocol can improve the number of retrieved and MII oocytes and probably the pregnancy outcomes after fresh embryo transfer in POR patients. However, larger randomized clinical trials are required to compare the pregnancy outcomes after this approach with other COH protocols with considering cost-effectiveness issue.Trial registrationIRCT20110731007165N9.The name of the registry: Ladan Kashani.The date of trial registration: 8.02.2020.

The Exploration of Poor Ovarian Response-Related Risk Factors: A Potential Role of Growth Differentiation Factor 8 in Predicting Ovarian Response in IVF-ET Patient.

Controlled ovarian hyperstimulation (COH) is the most common therapeutic protocol to obtain a considerable number of oocytes in IVF-ET cycles. To date, the risk factors affecting COH outcomes remain elusive. Growth differentiation factor 8 (GDF-8), a member of transforming growth factor β (TGF-β) superfamily, has been long discerned as a crucial growth factor in folliculogenesis, and the aberrant expression of GDF-8 is closely correlated with the reproductive diseases. However, less is known about the level of GDF-8 in IVF-ET patients with different ovarian response. In the present study, the potential risk factors correlated with ovarian response were explored using logistic regression analysis methods. Meanwhile, the expression changes of GDF-8 and its responsible cellular receptors in various ovarian response patients were determined. Our results showed that several factors were intensely related to poor ovarian response (POR), including aging, obesity, endometriosis, surgery history, and IVF treatment, while irregular menstrual cycles and PCOS contribute to hyperovarian response (HOR). Furthermore, POR patients exhibited a decrease in numbers of MII oocytes and available embryos, thereby manifesting a lower clinical pregnancy rate. The levels of GDF-8, ALK5, and ACVR2B in POR patients were higher compared with those in control groups, whereas the expression level of ACVR2A decreased in poor ovarian response patients. In addition, clinical correlation analysis results showed that the concentration of GDF-8 was negatively correlated with LH and estradiol concentration and antral follicle count. Collectively, our observations provide a novel insight of ovarian response–associated risk factors, highlighting the potential role of GDF-8 levels in ovarian response during COH process.

ADAMTS1 and HSPG2 mRNA levels in cumulus cells are related to human oocyte quality and controlled ovarian hyperstimulation outcomes

PurposeThe study investigated potential correlations between the expression levels of ADAMTS1 and HSPG2 in cumulus cells (CCs) and controlled ovarian hyperstimulation (COH) outcomes.MethodsRT-PCR was used to determine ADAMTS1 and HSPG2 mRNA levels in mice CCs at different timepoints (0, 4, 8, 12, and 16 h) after human chorionic gonadotropin (hCG) injection, and in CCs after RNAi treatment. Women with polycystic ovary syndrome (PCOS) (n = 45) and normal ovulatory controls (n = 103) undergoing IVF/ICSI were recruited. Relative ADAMTS1 and HSPG2 mRNA levels were measured by RT-PCR. Moreover, correlations of ADAMTS1 and HSPG2 levels with COH outcomes were analyzed.ResultsAt different timepoints after hCG treatment, ADAMTS1 mRNA had the highest level at 12 h, whereas HSPG2 showed opposite profiles to ADAMTS1 with the lowest level at 12 h. HSPG2 expression was upregulated after ADAMTS1 RNAi treatment The PCOS group had higher HSPG2 and lower ADAMTS1 expression levels than controls. In normal ovulatory women (control group), a higher expression of ADAMTS1 and lower expression of HSPG2 were associated with more mature oocytes, transplantable embryos, and good quality embryos, whereas higher transplantable embryo rates and good quality embryo rates were obtained only with lower HSPG2 expression. ROC curves showed the co-measurement of ADAMTS1 and HSPG2 had a better predictive power than separate analyses.ConclusionThe dynamic profiles of ADAMTS1 and HSPG2 were inversely correlated in CCs. In PCOS and normal ovulatory patients, higher ADAMTS1 and lower HSPG2 expression levels in CCs were related to better COH outcomes.

Ovarian Stimulation Is Safe and Effective for Patients with Gynecologic Cancer.

Purpose: To compare long-term outcomes of gynecologic cancer patients who pursued controlled ovarian hyperstimulation (COH) for fertility preservation (FP) with those who did not. Methods: Retrospective cohort, COH, and health outcomes in gynecologic cancer patients; data were analyzed by chi-square test, t-tests, and logistic regression. Results: Ninety patients with a gynecologic malignancy contacted the FP patient navigator: 45.6% (n = 41) had ovarian cancer, 25.6% (n = 23) endometrial cancer, 18.9% (n = 17) cervical cancer, 5.6% (n = 5) uterine cancer, and 4.4% (n = 4) multiple gynecologic cancers. From this cohort, 32 underwent COH, 43 did not, and 18 pursued ovarian tissue cryopreservation (OTC; 3 patients had both COH and OTC). Median age and type of cancer were not significantly different between the groups. COH patients had a range of 1-35 oocytes retrieved. Days to next cancer treatment in the COH group was 36 days; for those who declined COH, it was 22 days (not significant [NS], p > 0.05). There were two recurrences reported in the stimulation group and four in the no stimulation group (NS). Five deaths were reported, two in the stimulation group, none in the no stimulation group, and three in the OTC group (NS); 34% (n = 11) COH patients returned to use cryopreserved specimens, of which 45% (n = 5) had a live birth. Conclusion: Although time to next treatment was longer in the group of patients who underwent COH, this did not reach statistical significance. It appears that in selected patients with GYN malignancies, COH for oocyte or embryo cryopreservation is safe, with reasonable stimulation outcomes and no difference in long-term outcomes.

Changes and correlations of anti-Müllerian hormone and stem-cell factors in different ovarian reserve patients during GnRH-antagonist protocol and the effects on controlled ovarian hyperstimulation outcomes.

To explore the changes and correlations of anti-Müllerian hormone (AMH) and stem-cell factors (SCF) in different ovarian reserve patients during controlled ovarian hyperstimulation (COH) and the effects on COH outcomes. Serum at six different timepoints during GnRH-antagonist protocol and follicular fluid (FF) on oocyte retrieval day of 52 patients with polycystic ovary syndrome (PCOS), 61 patients with normal ovarian reserve (NOR) and 42 patients with diminished ovarian reserve (DOR) were collected. AMH and SCF were assessed using enzyme-linked immunosorbent assay. During COH, AMH in the PCOS group was the highest, but SCF did the opposite, and serum AMH gradually decreased, while SCF inversely increased. In the PCOS group, SCF on the first and fourth days of gonadotropin (Gn) administration was negative with Gn dosage (r = - 0.362, P < 0.05; r = - 0.344, P < 0.05). In the NOR group, the basal AMH was also negative with Gn dosage (r = - 0.297, P < 0.05) and positive with COH outcomes (number of retrieved oocytes, MII oocytes, and 2PN fertilization) as well as serum SCF after Gn administration. In the DOR group, both AMH and SCF were significantly associated with COH outcomes. Serum AMH in the DOR group after Gn administration and FF AMH showed a negative correlation with SCF. Serum AMH decreased, while SCF increased during COH. AMH and SCF are effective for Gn time and dosage adjustment and predicting COH outcomes for NOR and DOR patients. In addition, serum AMH in DOR patients after Gn administration and FF AMH has a negative effect on SCF.

Predictability of consecutive measurements of serum Anti-Mullerian Hormone (AMH) during In Vitro Fertilization (IVF)

Background : In recent years, many studies had been carried out on the basal AMH level and its association with controlled ovarian hyperstimulation (COH) outcome. Only a few studies have been conducted on the correlation between COH outcomes and AMH levels measured on different stimulation days and these studies did not show a comparison between different measurement timings over the entire period of the COH cycle. Objectives: the current study aim is to assess the predictive values of basal and consecutive serum AMH levels during COH cycle. Methods and Results: One hundred women were involved in this study, scheduled for IVF program in Dwarozh Fertility Center in Sulaimanyiah , between December 2015 until January 2017, blood samples were collected for measurement of AMH, Estradiol, and FSH on day 2 of menstrual cycle, and the subsequent samples on day 4,6,8 and 10 were taking after the stimulation of ovaries with gonadotrophin. All hormones being analyzed by using electrochemiluminescence methods (Cobas 411 by Roche) as a single batch, each patient was given a unique numerical identifier, which issued in data analysis. P values &lt;0.05 were considered significant. Results: the patients' characteristics , basal serum estradiol (E2), FSH and AMH levels at day 2 of cycle and&nbsp; subsequent days after stimulation . As expected significant differences were observed for total dosage of FSH, peak E2 levels and duration of stimulation between short and long GnRH agonist groups. The ROC curve was used to assess the&nbsp; AMH values in different days (day 2, 4, 6, 8, and 10) for prediction of IVF outcomes (implantation, abortion, preganancy and live birth). All the days showed significant area under the curve (AUC) (p&lt;0.05). However, when all the ROC curve were comapred to each others there were no significance differences bwteeen them (p&gt;0.05) Conclusions: &nbsp;The present study concluded that measurement of serum AMH at any time after stimulation still predictive of the IVF outcomes which will reinforce the already known value of AMH in clinical practice.

MTHFR C677T polymorphism is associated with follicle-stimulating hormone levels and controlled ovarian hyperstimulation response: a retrospective study from the clinical database

To evaluate the impact of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with clinical data analysis in controlled ovarian hyperstimulation (COH) of infertile women in the Intravenous Infusion Safety Evaluation Center of Hunan Province, People's Republic of China. Genetic Association Study. Reproductive medicine clinical. This genetic association study included 722 infertile women who received the standard long treatment protocol with accessible and complete electronic medical records. None. The clinical parameters were obtained from the Intravenous Infusion Safety Evaluation center. Basal FSH levels in the TT group were significantly higher than those of the CC group. The FSH levels after down-regulation in the TT group were higher than those of CC/CT genotypes. The TT genotype patients received significantly higher total doses of GnRH agonist and FSH compared with CC/CT genotypes, whereas the total dose of hCG was higher in the CT genotypes compared with the CC/TT genotypes. Further association analysis between hormone levels and COH outcomes indicated significantly negative correlation of basal FSH levels with antral follicle count and number of oocytes as well as the down-regulation FSH levels with the number of metaphase II oocytes and oocytes. The MTHFR C677T polymorphism was associated with high doses of ovarian stimulation medications, as well as higher FSH levels. The negative correlation between FSH levels and the number of oocytes suggested that C677T polymorphism may play a role in the poor prognosis of COH oocytes. This needs to be studied in future prospective studies with longer follow-up.

Levothyroxine supplementation on assisted reproduction technology (ART) outcomes in women with subtle hypothyroidism: a retrospective study

The need for treating subclinical hypothyroidism (SCH) in women undergoing assisted reproduction technology (ART) is under debate. Moreover, it is known that controlled ovarian hyperstimulation (COH) protocols may impair the thyroidal axis. Therefore, we evaluated if levothyroxine (L-T4) supplementation in SCH women before undergoing ART positively affects the main reproductive outcomes. We retrospectively analyzed in vitro fertilization (IVF) data of 4147 women submitted to 6545 cycles in a tertiary care IVF Center (January 2009–December 2014). L-T4 (1.4–2.0 mcg/kg) treatment was offered to all women with a pre-cycle TSH >2.5 mIU/L before starting COH and main ART outcomes were compared in euthyroid and L-T4-treated women undergoing ART. Among 4147 women, 1074 (26%) were affected by SCH and were treated with L-T4 before COH was started. No statistically significant differences among L-T4-treated and euthyroid women group were observed regarding pregnancy rate, respectively, per cycle (27.67% vs 26.37%; p = .314) and per embryo transfer (30.13% vs 29.17%; p = .489), live birth rate, respectively, per cycle (21.58% vs 20.38%; p = .304) and per embryo transfer (23.49 vs 22.54%; p = .449) and the rest of primary and secondary efficacy endpoints. Early L-T4 treatment for infertile women with a subtle thyroid dysfunction may mitigate and protect from the negative effects of SCH in the setting of ART, and may preventively overcome also the negative impact of COH on thyroidal axis.

Calcium infusion plus or minus cabergoline for prevention of ovarian hyperstimulation syndrome: Randomized double-blind placebo-controlled trial

Aim: To evaluate the interaction of adding oral cabergoline (OC) to calcium infusion as a preventive modality for ovarian hyperstimulation syndrome (OHSS) in risky women undergoing controlled ovarian hyperstimulation (COH) in context of in- vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI).Patients and Methods: This prospective, double-blind, randomized, placebo-controlled trial was conducted at Benha IVF center of Obstetrics and Gynecology Department of Benha University and Nour Al Hayah Fertility Center Between January 2015 and February 2016. 220 risky women for OHSS undergoing ICSI were included, they were randomized to 110 women received once daily OC for eight days, starting at HCG triggering and infusion of calcium gluconate 10 ml 10% in 200 ml 0.9% saline daily for 4 days beginning at ovum pick up (OPU), coined as calcium infusion plus group (CI+) and 110 women received only calcium infusion in the same fashion as in CI+ coined as calcium infusion minus group (CI-). The primary outcome was the overall incidence of OHSS while the secondary issues were OHSS types and grades as well as other ICSI outcomes.Results: The incidence of overall OHSS was significantly lower in calcium infusion plus oral cabergoline (CI+) group compared to calcium infusion alone (CI-) group [8/110(7.2%) in CI+ versus 18/110 (16.3%) in CI- with difference in proportion percentage point (ΔPP)=-9.1%, 95% CI: -0.49, -17.4; P = 0.036]. Despite the incidence of moderate and severe OHSS was lower in CI+ than in CI-, this difference didn't reach the significance level (2.7% vs 5.4%; p = 0.3) and (0.9% versus 2.7%; ), respectively. The other COH and ICSI outcomes didn't show any statistically significant differences.Conclusion: Adding oral cabergoline to calcium infusion is effective than calcium infusion alone in the reduction of overall OHSS incidence as well as its severity at comparable pregnancy outcomes

Anti-Müllerian hormone levels to predict oocyte maturity and embryo quality during controlled ovarian hyperstimulation.

The aim of this study was to assess the correlation between controlled ovarian hyperstimulation (COH) outcome parameters and anti-Müllerian hormone (AMH) serum levels during in vitro fertilization (IVF) treatment in women with varying ovarian reserve levels. Prospective study of 46 women undergoing GnRH-antagonist short protocol for IVF. Participants included women with low ovarian reserve (N.=11), normoreserve (N.=16), and polycystic ovarian syndrome (PCOS; N.=19). AMH was measured on menstrual cycle day 1-3 (basal AMH), on the day of GnRH-antagonist administration (AMH-GnRH), on the day of hCG administration (AMH-hCG), and in follicular fluid on the day of oocyte retrieval (AMH-FF). Basal AMH was significantly correlated (P<0.001) with antral follicle count and number of follicles >11mm on hCG day (P<0.05). Both basal AMH and AMH-GnRH were significantly correlated (P<0.05) with the number of oocytes retrieved and metaphase II. AMH-hCG was correlated with top quality embryos (P=0.04). No correlations were found between COH outcome parameters and AMH-FF. Basal AMH serum concentration was the strongest predictor of oocyte yield. AMH concentration at the mid-follicular phase was also a good predictor of oocyte yield and this marker was the only useful ovarian reserve indicator during the follicle growth process to predict IVF outcomes. AMH-hCG levels appear to predict embryo quality. AMH levels during the COH can provide valuable data to help individualize treatment and predict COH results.

Controlled ovarian stimulation and triggers in in vitro fertilization: protocol personalization key to optimize outcomes.

The past four decades have delivered many advancements to improve in vitro fertilization (IVF) outcomes. These include a delicate balance of controlled ovarian hyperstimulation (COH) without causing ovarian hyperstimulation syndrome (OHSS), a safe oocyte retrieval, fertilization and embryo culture, endometrial growth and receptivity to promote implantation, and luteal support to maintain the pregnancy. Contemporary IVF practice includes both the classic COH protocols as well as protocols for poor responders and those for specific patient populations. An assortment of agents have been developed and utilized in various combinations to improve COH outcomes and promote oocyte maturation while decreasing the risk of OHSS. Various protocols have evolved over time. Ideal practices involve selecting the optimal protocol for a personalized, patient-specific stimulation and trigger.

Steroid hormone pretreatments in assisted reproductive technology.

Adequate availability and FSH sensitivity of ovarian antral follicles and coordination of their growth during controlled ovarian hyperstimulation (COH) rank among factors that may determine outcome, particularly in patients presenting ovarian function defects and so-called "poor responders." Growing evidence indicates that both factors are positively influenced by steroid hormone pretreatments. First, data from studies conducted in both animals and in women exposed to virilizing androgen doses indicate that androgen pretreatments may increase follicle responsiveness to FSH and/or the number of growing follicles in the ovary, thereby constituting an interesting perspective in the management of "poor responders." Second, overcoming pre-COH heterogeneities in antral follicle sizes, which are more pronounced in "poor responders," to achieve adequate coordination of multiple follicular growth during COH also is contributive. For this, suppression or attenuation of the premature FSH increase during the preceding late luteal phase using sex steroid pretreatments (oral contraceptives, synthetic progestogens, or estradiol), or additional strategies such as premenstrual GnRH antagonist administration has been shown to be effective. The present paper will critically review proposed mechanisms and clinical results of sex steroid hormone pretreatments in these two different indications as an effort to optimizing COH outcome.

Anti-Mullerian hormone as a predictor of ovarian reserve in ART protocols: the hidden role of thyroid autoimmunity.

BackgroundProtocols of controlled ovarian hyper-stimulation (COH) require, as a crucial step, the identification of reliable predictors of ovarian reserve. Anti-Mullerian hormone (AMH) is one of the most reliable predictors of ovarian reserve but other factors including autoimmune thyroid diseases (ATD) have been associated with reduced fertility and poor COH outcome. Aim of the present study was to evaluate the relationship between ATD and AMH, and their role on the outcome of COH.MethodsThe study group included 288 sub-fertile euthyroid women aged less than 40 years attending a single center for Reproductive Medicine. Among them, 55 were ATD-positive and 233 ATD-negative. The serum levels of AMH, FSH, LH, estradiol (E2), and TSH were measured before COH. The ratio between serum E2 concentration on the day of oocytes pick-up and the total dose of administered recombinant FSH (r-FSH) (E2/r-FSH ratio) was calculated.ResultsThe serum levels of AMH were significantly related to E2/r-FSH ratio, total dose of r-FSH and number of M II oocytes, both in ATD-positive and ATD-negative women. Within the low stratum of AMH levels, the presence of ATD did not further affect the outcome of COH. When the serum levels of AMH were in the high stratum, the presence of ATD significantly affected the E2/rFSH ratio, the total dose of r-FSH and the number of M II oocytes.ConclusionsThe probability of a poor response to COH is high, and independent from ATD, in women with low AMH serum levels. In women with a good ovarian reserve, as assessed by high AMH serum levels, the presence of ATD impairs the outcome of COH.

The dynamic changes of anti-Mullerian hormone and inhibin B during controlled ovarian hyperstimulation in decreased ovarian reserve women and the effect on clinical outcome

Objective: To investigate the dynamics of anti-Mullerian hormone (AMH) and inhibin B (INHB) levels during controlled ovarian hyperstimulation (COH) in women with decreased ovarian reserve (DOR), and assess the effect of these dynamic changes on the prediction of clinical outcome in in-vitro fertilization (IVF).Methods: A total of 124 women undergoing IVF cycles were divided into normal ovarian reserve (NOR) and DOR groups. AMH and INHB levels were measured in serum on menstrual cycle day 2 or 3 (D2/3), day 5 of stimulation (D5), hCG day (D-hCG) and follicular fluid (FF) on oocyte retrieval day.Results: Serum AMH levels were gradually decreased while INHB levels were gradually increased from D2/3 to D-hCG during the COH in both groups. Serum AMH, INHB levels on D2/3 and FF AMH, INHB levels were highly positively correlated with AFC and oocytes retrieval. Multivariate logistic regression analysis revealed that clinical pregnancy did not directly correlate with serum and FF AMH and INHB levels.Conclusion: Serum AMH and INHB levels were not directly related to clinical pregnancy, dynamic serum AMH and IHNB levels were positively correlated with COH outcomes.

Ovarian cyst aspiration prior to in vitro fertilization treatment for subfertility.

Ten per cent to 15% of couples have difficulty in conceiving. A proportion of these couples will ultimately require assisted reproduction. Prior to controlled ovarian hyperstimulation (COH) a baseline ultrasound is performed to detect the presence of ovarian cysts.Previous research has suggested that there is a relationship between the presence of an ovarian cyst prior to COH and poor outcome during IVF. The aim of this review was to determine the effectiveness and safety of functional ovarian cyst aspiration prior to ovarian stimulation versus a conservative approach in women with an ovarian cyst who were undergoing IVF or ICSI. We searched the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov, Google Scholar and PubMed. The evidence was current to April 2014 and no language restrictions were applied. We included all randomised controlled trials (RCTs) comparing functional ovarian cyst aspiration versus conservative management of ovarian cysts that have been seen on transvaginal ultrasound (TVS) prior to COH for IVF or ICSI. Ovarian cysts were defined as simple, functional ovarian cysts > 20 mm in diameter. Oocyte donors and women undergoing donor oocyte cycles were excluded. Study selection, data extraction and risk of bias assessments were conducted independently by two review authors. The primary outcome measures were live birth rate and adverse events. The overall quality of the evidence for each comparison was rated using GRADE methods. Three studies were eligible for inclusion (n = 339), all of which used agonist protocols. Neither live birth rate nor adverse events were reported by any of the included studies. There was no conclusive evidence of a difference between the group who underwent ovarian cyst aspiration and the conservatively managed group in the clinical pregnancy rate (OR 1.40, 95% CI 0.67 to 2.94, 3 studies, 339 women, I(2) = 0%, low quality evidence). This suggested that if the clinical pregnancy rate in women with conservative management was assumed to be 5%, the chance following cyst aspiration would be between 4% and 14%. There was no evidence of a difference between the groups in the mean number of follicles recruited (0.55 follicles, 95% CI -0.48 to 1.59, 2 studies, 159 women, I(2) = 0%, low quality evidence) or mean number of oocytes collected (0.41 oocytes, 95% CI -0.04 to 0.85, 3 studies, 339 women, I(2) = 0%, low quality evidence). Findings for the cancellation rate (two studies) were inconsistent but neither study reported a benefit for the aspiration group. The main limitations of the evidence were imprecision, inconsistency, questionable applicability, and poor reporting of study methods. There is insufficient evidence to determine whether drainage of functional ovarian cysts prior to controlled ovarian hyperstimulation influences live birth rate, clinical pregnancy rate, number of follicles recruited, or oocytes collected in women with a functional ovarian cyst. The findings of this review do not provide supportive evidence for this approach, particularly in view of the requirement for anaesthesia, extra cost, psychological stress and risk of surgical complications.