Ovarian Hyperstimulation Syndrome In Women Research Articles

O-043 Con

Abstract Dual and/or double trigger improve IVF success - CON The improvement of in vitro fertilization (IVF) outcomes remains a pivotal area of reproductive medicine research, with the dual trigger approach emerging as a significant innovation. This con abstract explores the scientific basis, methodology, and outcomes associated with the dual trigger strategy, juxtaposed with conventional triggering methods in IVF protocols. The dual trigger, incorporating both Gonadotropin-Releasing Hormone Agonist (GnRHa) and Human Chorionic Gonadotropin (hCG), has been posited to improve oocyte maturation, retrieval-, and live birth rates. By scrutinizing recent studies, clinical trials, and meta-analyses, this debate aims to delineate the efficacy, safety, and application scope of this approach. Initial investigations into the dual trigger method have highlighted its potential to ameliorate oocyte quality and maturity, which are crucial determinants of IVF success. The mechanism underlying this improvement involves the simultaneous activation of LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone) receptors, enhancing follicular response and oocyte developmental competence. Studies have demonstrated an increase in the number of mature oocytes retrieved, attributed to the more synchronized and comprehensive follicular stimulation afforded by the dual trigger. This augmentation in oocyte quality and quantity directly correlates with enhanced embryo development profiles, and higher implantation and clinical pregnancy rates. Furthermore, the dual trigger method has shown promise in reducing the incidence of Ovarian Hyperstimulation Syndrome (OHSS), a severe complication of IVF treatments. By leveraging the luteolytic effects of GnRHa, this strategy minimizes the risk associated with exogenous hCG administration, thus offering a safer alternative for patients predisposed to OHSS. The application of the dual trigger in specific patient cohorts, such as those with PCOS or poor ovarian responders, has been underlined, indicating its potential for personalized reproductive medicine. However, the implementation of the dual trigger strategy is not without challenges. Variability in patient response necessitates a highly individualized approach, with precise dosing and timing adjustments to optimize outcomes. The existing literature presents a heterogeneity in study designs, populations, and outcome measures, which complicates the direct comparison of dual trigger efficacy against traditional methods. Furthermore, the long-term safety and potential impacts on offspring warrant further investigation, given the recent adoption of this approach. In conclusion, the dual trigger strategy may offer significant benefits in enhancing IVF outcomes. Its potential to improve oocyte maturity and quality could increase the number of retrievable oocytes and reduce the incidence of OHSS. However, it is important to acknowledge that, while the GnRH agonist trigger combined with a freeze-all strategy eliminates the risk of OHSS in women with PCOS, the dual trigger approach followed by fresh embryo transfer does not. Further research is imperative to refine its application, understand its mechanisms fully, and establish comprehensive guidelines for its use. The promise of the dual trigger approach underscores the importance of continuous innovation and evidence-based practices in enhancing the efficacy and safety of IVF treatments.

Expression of concern to “Can dopamine agonist at a low dose reduce ovarian hyperstimulation syndrome in women at risk undergoing ICSI treatment cycles? A randomized controlled study” [EJOG 165(2) (2012) 254–258]

Expression of concern to “Can dopamine agonist at a low dose reduce ovarian hyperstimulation syndrome in women at risk undergoing ICSI treatment cycles? A randomized controlled study” [EJOG 165(2) (2012) 254–258]

Age at menarche and risk of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI cycles: a retrospective cohort study

ObjectivesWe aimed to explore the association between age at menarche (AAM) and ovarian hyperstimulation syndrome (OHSS) in fresh in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles.DesignA retrospective cohort study.SettingData were...

Estradiol-to-follicle ratio on human chorionic gonadotropin day is a novel predictor of gestational diabetes mellitus in women receiving fresh embryo transfer.

To assess the predictive value of estradiol (E2) related parameters on the incidence of gestational diabetes mellitus (GDM) in women undergoing fresh embryo transfer. A Post-hoc analysis of a prospective cohort study. We identified an optimal E2/follicle (E2/F) ratio threshold of 246.03 pg/ml on the day of human chorionic gonadotropin (hCG) administration. Women with an E2/F ratio exceeding this threshold had significantly lower rates of GDM (12.75% vs. 20.41%, P < 0.001) and ovarian hyperstimulation syndrome (OHSS) (11.75% vs. 15.48%, P = 0.03). Additional E2 parameters were also evaluated: baseline E2, E2 on hCG day, E2 increase, and E2 fold change. Lower GDM rates were observed in women with baseline E2 above 31.50 pg/ml (13.51% vs. 19.42%, P <0.01), E2 on hCG day above 3794.50 pg/ml (12.26% vs. 19.32%, P < 0.001), and E2 increase above 3771.50 pg/ml (12.24% vs. 19.28%, P < 0.001). There were no significant differences in OHSS rates for these additional E2 parameters. After adjusting for confounders, lower E2/F ratio (OR: 1.626, 95% CI: 1.229-2.150, P <0.01), E2 on hCG day (OR: 1.511, 95% CI: 1.133-2.016, P = 0.01), and E2 increase (OR: 1.522, 95% CI: 1.141-2.031, P <0.01) were identified as risk factors for GDM. This study demonstrates that an E2/F ratio over 246.03 pg/ml is significantly associated with a reduced risk of both GDM and OHSS in women undergoing fresh embryo transfer, highlighting the E2/F ratio as a superior predictive biomarker compared to other E2-related parameters.

Optimising IVF Outcomes

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, with an overall prevalence of 5% to 15%, and a frequent cause of infertility. Ovulation disorders are the main cause of infertility for the couples. A range of endocrine and metabolic traits are also associated with PCOS and these include obesity, dyslipidemia, insulin resistance, hyperinsulinism and an increased risk of type 2 diabetes mellitus and cardiovascular disease. Studies have found that women with PCOS had a higher live birth rate, clinical pregnancy rate and implantation rate, as well as an increased risk of ovarian hyperstimulation syndrome (OHSS), pregnancy complications including miscarriage, preterm delivery, gestational diabetes mellitus and pregnancy-induced hypertension in their first IVF treatment when compared with non-PCOS controls. During the past three decades, applying IVF for infertility treatment PCOS women has increased significantly, and the landscape of treatment strategies has changed dramatically. GnRH agonist triggering oocyte maturation combined with freeze-all embryos is an effective and commonly used protocol nowadays to achieve good success rate as well as to minimize the risk of OHSS in women with PCOS. Recently, there has been an increasing use of oocyte in-vitro maturation (IVM) for treating infertility in women with PCOS. IVM technique could be considered as an alternative to IVF in centers where it is available. However, strategies to minimize pregnancy complications in women with PCOS remain further studied.

Risk of ovarian hyperstimulation syndrome in women with malignancies undergoing treatment with long-acting gonadotropin-releasing hormone agonist after controlled ovarian hyperstimulation for fertility preservation: a systematic review.

Fertility preservation is an important quality of life issue for women of reproductive age undergoing gonadotoxic treatment. The possibility of administering an adjuvant long-acting gonadotropin-releasing hormone agonist (GnRHa) with the aim of reducing the number of follicles susceptible to the effects of chemotherapy and thus reducing the risk of ovarian damage is considered in some international society guidelines, particularly in certain cancers such as breast cancer. Nowadays, the administration of long-acting GnRHa after controlled ovarian hyperstimulation (COH) for fertility preservation by cryopreservation of oocytes or embryos is increasingly used. However, cases of ovarian hyperstimulation syndrome (OHSS) have been reported following the use of long-acting GnRHa after COH for fertility preservation, indicating that the potential adverse effects of this treatment need to be further investigated. The aim of this systematic review was to comprehensively characterize patients who developed OHSS after treatment with long-acting GnRHa following COH for fertility preservation. A comprehensive search of major electronic databases through January 2023 was performed. Studies reporting the use of long-acting GnRHa after COH for fertility preservation and the development of OHSS were included. Risk of bias was assessed using a modified version of the Newcastle-Ottawa scale. Results were synthesized qualitatively. Three studies with five patients met the eligibility criteria. The majority of patients were diagnosed with breast cancer and all patients underwent COH for oocyte cryopreservation. OHSS occurred in all patients after administration of long-acting GnRHa. The interval between ovulation induction and administration of long-acting GnRHa thereafter ranged from 3 to 5 days. All patients were treated conservatively and recovered without complications. Current evidence suggests that the use of long-acting GnRHa after COH for fertility preservation may be associated with OHSS. Healthcare providers should thoroughly discuss the benefits and risks of this intervention with their patients before making a decision. Further studies are needed to fully elucidate the causal relationship between long-acting GnRHa and OHSS in this population.

O-009 Controlled ovarian stimulation (COS) protocols for assisted reproduction: a Cochrane systematic review and network meta-analysis

Abstract Study question What is the relative effectiveness and safety of existing COS protocols for women undergoing assisted reproductive technology (ART) treatment? Summary answer There was no difference in live birth between all protocols, but short antagonist protocols may reduce ovarian hyperstimulation syndrome in women with predicted normal/high response. What is known already Controlled ovarian stimulation is an essential step in most ART cycles. It involves the administration of exogenous gonadotrophins to induce multifollicular growth, usually in addition to drugs that prevent untimely ovulation by suppressing the pituitary gland. Different treatment combinations may be used in COS. These vary according to the type of drugs administered for pituitary suppression (e.g., gonadotrophin-releasing hormone [GnRH] agonists, antagonists) and ovarian stimulation (e.g., urinary or recombinant gonadotrophins). Drug dosages, timing and routes of administration also vary between different regimens. However, there is no consensus on how the existing COS protocols rank according to their effectiveness and safety. Study design, size, duration We searched the following databases to November 2021: MEDLINE, EMBASE, CINAHL, CENTRAL and ClinicalTrials.gov. We included randomised controlled trials (RCTs) comparing at least two COS protocols using GnRH agonists or antagonists for pituitary suppression; and human menopausal gonadotrophin (hMG), urinary or recombinant follicle-stimulating hormone (u/rFSH), with or without luteinising hormone (LH) for ovarian stimulation. The primary outcomes were the rates of live birth (LBR) and ovarian hyperstimulation syndrome (OHSS) per participant after one stimulation cycle. Participants/materials, setting, methods Two reviewers independently selected studies and extracted data. We conducted pairwise and network meta-analyses (NMA) according to participants’ predicted response to COS (normal, high and low). Using the Cochrane-RoB-1 tool, we restricted our primary analyses to RCTs at low risk of selection and other biases. We presented effect estimates as risk ratio (RR) with 95% confidence interval (CI) and considered I2&amp;gt;50% as representing substantial heterogeneity. For each outcome, we generated ranking plots comparing different interventions. Main results and the role of chance In total, our searches identified 9464 studies. The primary analysis included 68 RCTs assessing 17861 women and 34 different COS protocols. The evidence showed that in women with predicted normal or high response, the use of short GnRH antagonist protocols may result in little to no difference in LBR (RR 0.98, 95% CI 0.85 to 1.13; 6 studies; 2063 women; I2 = 0%; low-certainty evidence) and a reduction in OHSS (RR 0.88, 95% CI 0.78 to 0.99; 7 studies; 2246 women; I2 = 0%; low-certainty evidence) compared with long GnRH agonist protocols. The rankogram comparing different COS protocols showed a probability of 98% that short GnRH antagonist regimens are the best treatment to prevent OHSS. Sensitivity analyses including all studies showed that in women with predicted normal response undergoing long GnRH agonist cycles for pituitary suppression, the use of rFSH for ovarian stimulation may result in decreased fresh-cycle LBR compared to hMG (RR 0.80, 95% CI 0.68 to 0.95; 7 studies; 1575 women; I2 = 1%; low-certainty evidence). For the remaining interventions (e.g., agonist flare or progestogens for pituitary suppression, in combination with various gonadotrophin regimens) the evidence was uncertain of an effect or insufficient for quantitative synthesis. Limitations, reasons for caution The high number of interventions resulted in disconnected networks, limiting our ability to perform NMA for some comparisons. The certainty of the evidence was limited by serious risk of bias. Finally, the lack of data on cumulative LBR and differences in oocyte yield made comparisons between FSH preparations potentially unbalanced. Wider implications of the findings Our findings suggest that the use of short GnRH antagonist protocols may result in reduced OHSS rates in women with predicted normal or high ovarian response without compromising live birth rates. There is a paucity of high-quality RCTs comparing different gonadotrophin preparations (e.g., hMG versus rFSH) for COS. Trial registration number N/A

P-698 Pituitary functioning gonadotroph adenomas (FGA)-induced ovarian hyperstimulation syndrome (OHSS): results from tertiary neuroendocrine centres in the UK

Abstract Study question There are no published series of OHSS due to FGA. What FGA features should clinicians look for during OHSS, and what treatments are effective? Summary answer FGA tumour size is always &amp;gt;10mm. Other pituitary hormones may be deficient. Surgical resection of FGA is an effective treatment for OHSS. What is known already Pituitary adenomas affect 1:1000 adults and are classified as functioning or non-functioning. Non-functioning pituitary adenomas do not secrete hormones, but most commonly stain histologically gonadotroph cells. Functional pituitary adenomas secrete hormones such as prolactin causing prolactinoma. However, it is rare for a pituitary tumour to cause clinical features of excessive gonadotrophins (functioning gonadotroph adenoma; FGA). Single case reports, but no case series, have been published on the presentation of FGA-induced OHSS in women. Surgical excision of adenomas has been reported to cause remission of symptoms, though systematic data are lacking owing to rarity of these tumours. Study design, size, duration National case series from tertiary neuroendocrine units in England, Wales and Scotland. Participants/materials, setting, methods Eight high-volume pituitary endocrine tertiary units within England, Wales and Scotland audited their records for any cases of FGA-induced OHSS; only seven patients have been identified to date. In all cases, there had been no recent exposure to assisted reproductive technologies (ART) or drugs known to induce OHSS including gonadotrophins or selective oestrogen receptor modulators (SERMS). Main results and the role of chance Seven cases of FGA were identified with mean age 31.6 years (range 16-48) at diagnosis. Two-of-seven women presented acutely unwell with abdominal pain, distention and palpable mass requiring oophorectomy for ovarian torsion/ruptured ovarian cyst. The remaining five women presented with abdominal pain (n = 2), thyrotoxicosis (n = 1), menstrual irregularities/galactorrhoea (n = 1) and visual disturbances (n = 1). All women experienced intermittent pelvic pain during medical attendance. Pelvic ultrasound demonstrated enlarged multiseptated ovaries (volume ranging 27-442cm3). Ascites was noted in one woman. Six women had visual field defects due to optic chiasm compression on formal assessment. Median FSH was 26.10 u/L (8.3-33), but LH was &amp;lt;2.5 u/L in all cases. Estradiol (E2) far exceeded the reference range in 5/7 women (2990 to &amp;gt; 18000pmol/L);E2 was at the upper limit of normal in the remaining 2/7 women (960-1450pmol/L). Hyperprolactinaemia, hyperthyroidism and other pituitary hormones deficiency were noted in 6/7, 1/7 and 4/7 women respectively. All FGAs were macroadenomas with diameters ranging 16-48mm. Two patients were administered a somatostatin analogue prior to surgery, but FSH, E2 and tumour size did not change. Transsphenoidal surgery was performed in 6/7 women, and always improved symptomatic and biochemical features of OHSS; however, residual FGA tumour was present post-operatively in all cases studied. Limitations, reasons for caution It is possible that some ‘non-functioning’ gonadotroph adenomas cause subclinical problems including menstrual irregularity and mild OHSS which were never diagnosed. We have insufficient data to determine the prognosis for future pregnancy after FGA-induced OHSS. This study utilised historical case-notes, so some data is missing. Wider implications of the findings The ‘spontaneous’ presentation of OHSS may be confusing for clinicians. We report that FGA is an important cause of spontaneous OHSS which has well-defined biochemical and radiological characteristics, which may be treated effectively in the short-to-medium with pituitary surgery. Results of this study may provide greater awareness of FGA-induced OHSS. Trial registration number N/A

Antral follicle count and anti-Müllerian hormone level as predictors of ovarian hyperstimulation syndrome in women with polycystic ovarian syndrome undergoing controlled ovarian stimulation.

Aim: To compare the rate of ovarian hyperstimulation syndrome in women with and without polycystic ovarian syndrome, and to determine the cut-off for the antral follicle count and the anti-Müllerian hormone level predictive of ovarian hyperstimulation syndrome in both groups. Methods: This was a prospective cohort study conducted in women aged 20–35 years who were undergoing controlled ovarian stimulation. The women were divided into those with polycystic ovarian syndrome and the controls on the basis of the Rotterdam criteria. The outcome of stimulation was recorded, and the ovarian response markers were compared in both groups. Results: Among 689 women included in the study, 276 (40.1%) had polycystic ovarian syndrome, and 476 (59.9%) were used as the controls. Ovarian hyperstimulation syndrome occurred in 19.6% of the cases, and in 7.7% of the controls (p <0.001). The conception rate was greater in the group of cases (52.5% vs. 16.5%, p = 0.001). Among the cases, the sensitivity and specificity for the prediction of hyper-response were 94.4% and 97.3% for AFC, and 92.6% and 93.7% for the anti-Müllerian hormone, at the cut-off values of ≥18 and ≥6.425 ng/ml, respectively. Among the controls, the sensitivity and specificity for the prediction of hyper-response were 93.8% and 97.1% for the antral follicle count, and 93.6% and 94.5% for the anti-Müllerian hormone, at the cut-off values of ≥10 and ≥3.95 ng/ml, respectively. Conclusion: Group-specific values should be used to identify and counsel women undergoing controlled ovarian stimulation. In light of available evidence, gynaecologists should be trained to perform ultrasound evaluation, determine the antral follicle count of their patients, and offer them appropriate counselling.

Prednisone combined with letrozole reduced risk of ovarian hyperstimulation syndrome (OHSS) in women undergoing long-term gonadotropin-releasing hormone analog treatment.

Ovarian hyperstimulation syndrome (OHSS) is a severe disease that can lead to serious complication. Letrozole has been applied during controlled ovarian hyperstimulation (COH) to reduce the rate of OHSS in women undergoing long-term Gonadotropin-releasing Hormone Analog (GnRHa) treatment for assisted fertility. Prednisone can prevent vasodilatation and increased vascular permeability, which is common during OHSS. However, few studies have evaluated the combined effect of letrozole and prednisone in preventing severe OHSS and is the aim of our retrospective study of patients receiving GnRHa treatment. A total of 296 women who accepted autologous in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included in this retrospective study. There were three groups: 146 women had letrozole, including letrozole alone (LE group, n=60) and letrozole with prednisone (LE + Pre group, n=86), and 150 women had no treatment (C group). Severe OHSS was diagnosed according to clinical evidence of hydrothorax, severe dyspnea, oliguria/anuria, and intractable nausea/vomiting. The addition of prednisone to letrozole successfully reduced the occurrence rate of severe OHSS than those women administered letrozole alone (55.0% vs. 70.6%, P=0.022). However, the ongoing pregnancy rate was lower in the LE + Pre group than that in the LE-alone group (64.3% vs. 87.0%, P=0.025). Surprisingly, progesterone level on the trigger day (>0.895 ng/mL) is a strong predictor for pregnancy failure with a specificity of 68.3% and sensitivity of 65.7% in the LE-alone group. Treatment with a combination of letrozole and prednisone may lower the rate of severe OHSS in women with prolonged gonadotropin-releasing hormone agonist protocol during assisted fertility treatment. When the progesterone level on trigger day is over 0.895 ng/mL, letrozole treatment may negatively affect clinical pregnancy.

Does the timing of cabergoline administration impact rates of ovarian hyperstimulation syndrome?

ObjectiveDoes the timing of cabergoline administration impact the rate of mild/moderate ovarian hyperstimulation syndrome in women with a GnRH agonist trigger?MethodsWe conducted a retrospective cohort analysis of 285 in-vitro fertilization patients at risk of OHSS who received a GnRH agonist trigger from 2011 to 2019 at McGill University Health Centre. Group 1 (Trig, n=101) began taking cabergoline 0.5 mg orally for 7 days at the time of GnRH agonist trigger, while Group 2 (Retriev, n=184) started taking cabergoline on the day of oocyte retrieval. The rates of OHSS were then compared between the groups using analysis of variance and chi-square analysis, where appropriate.ResultsThe baseline demographic characteristics of the two groups were similar. Trig appeared to be at a slightly higher risk of OHSS based on a significantly higher antral follicle count (20.2±4.2 vs. 19.0±4.3; P=0.02), higher number of stimulated follicles >10 mm at trigger (25.7±7.0 vs. 22.8±8.3, P=0.003), and higher peak serum E2 level (17,325±2,542 vs. 14,822±3,098; P=0.0001). The Trig group had lower rates of mild and moderate OHSS (24% vs. 36%; P=0.045). Neither group had any patients who developed severe OHSS. Trig had fewer patients presenting with pelvic free fluid (13% vs. 23%; P=0.03), lower hematocrit (37.8±4.8% vs. 40.5±4.2%; P=0.0001), higher albumin concentrations (30.4±2.7 vs. 29.5±2.0; P=0.01), and lower potassium concentrations (3.9±0.5 vs. 4.2±0.7; P=0.0002).ConclusionCabergoline at the time of trigger as compared to the time of collection should be investigated to assess its role in reducing the rates of mild/moderate OHSS.

Dopamine agonists for preventing ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment. OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment. We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature. We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events. Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence. The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. Thedopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention(OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that ifthe risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%.We are uncertain of the effect of dopamine agonists on rates of live birth(OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists onclinical pregnancy, multiple pregnancy,miscarriageor adverse events(very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention(OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth(OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancyandmiscarriage, but we are uncertain if they improve rates ofmultiple pregnancy or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSScompared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates oflive birth(OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported. Dopamine agonists probably reduce the incidence of moderate or severe OHSScompared to placebo/no intervention, while we are uncertain of the effect onadverse events andpregnancy outcomes (live birth, clinical pregnancy,miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.

The effect of different endometrial preparations on women with polycystic ovary syndrome undergoing initial frozen embryo transfer: A historical cohort analysis.

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. 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. 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). 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.

Association of Metformin With Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization

Metformin is widely used among women with polycystic ovary syndrome (PCOS). However, its associations with outcomes of in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in women with PCOS remain controversial. To assess whether metformin is associated with improved outcomes of IVF/ICSI-ET in women with PCOS. PubMed, Embase, and Cochrane were searched from database inception to January 31, 2020. Only randomized clinical trials (RCTs) were included. Eligible studies enrolled women with PCOS undergoing infertility treatment with IVF/ICSI-ET and reported at least 1 outcome of IVF/ICSI-ET. This study followed the Preferred Reporting Items for Systematic Reviews and Meta analyses guidelines. Two authors independently extracted the data. Study quality was evaluated using the GRADE system. Treatment effect was quantified using odds ratios (ORs) with 95% CIs using random-effect models with the Mantel-Haenszel method. Ovarian hyperstimulation syndrome (OHSS), clinical pregnancy rate, and live birth rate. A total of 12 RCTs, which collectively included 1123 women with PCOS undergoing infertility treatment with IVF/ICSI-ET, were identified. The risk of OHSS in women randomized to metformin was lower than in women not randomized to metformin (OR, 0.43; 95% CI, 0.24-0.78), although this difference was not significant for women with PCOS with a body mass index of less than 26 (OR, 0.67; 95% CI, 0.30-1.51). There was no significant difference in clinical pregnancy rate (OR, 1.24; 95% CI, 0.82-1.86) or live birth rate (OR, 1.23; 95% CI, 0.74-2.04) in the total population studied. However, in a post hoc analysis among women with a body mass index of 26 or greater, metformin treatment was associated with increased clinical pregnancy rates (OR, 1.71; 95% CI, 1.12-2.60). In this study, metformin treatment was associated with a decreased risk of OHSS but had no association with the overall clinical pregnancy rate or live birth rate among women with PCOS undergoing IVF/ICSI-ET. Metformin treatment should be carefully considered for women with PCOS undergoing IVF/ICSI-ET and may be more preferred for women with a body mass index greater than 26.

Prediction of severe ovarian hyperstimulation syndrome in women undergoing in vitro fertilization using estradiol levels, collected ova, and number of follicles.

ObjectiveOur objective was to determine whether estradiol (E2) levels (Day 3 and fold change to Day 10), antral follicle count (AFC), and number of ova collected could predict ovarian hyperstimulation syndrome (OHSS) and culdocentesis intervention.MethodsWe conducted a retrospective review of patient charts between January 2008 and December 2017. OHSS was defined using American Society for Reproductive Medicine criteria. Predictability was evaluated by measuring the area under the receiver operating characteristic curve (AUC).ResultsThe cohort included 319 women (166 controls, 153 OHSS, of whom 54 had severe OHSS). The OHSS group had higher E2Day 3 (249 ± 177 vs. 150 ± 230 ng/L), E2FoldChange (32.2 ± 29.1 vs. 20.1 ± 23.8), AFC (18.2 ± 9.1 vs. 11.6 ± 8.3), and number of ova collected (21.1 ± 9.0 vs. 10.1 ± 6.5). E2Day 3 (AUC = 0.76, 95%CI: 0.71–0.82), E2FoldChange (AUC = 0.71, 95%CI: 0.65–0.77), AFC (AUC = 0.75, 95%CI: 0.70–0.81), and number of ova collected (AUC = 0.85, 95%CI: 0.81–0.89) were predictive for OHSS. All variables were predictive for culdocentesis intervention (E2Day 3: AUC = 0.63, 95%CI: 0.55–0.70; E2FoldChange: AUC = 0.63, 95%CI: 0.55–0.71; AFC: AUC = 0.74, 95%CI: 0.68–0.80; number of ova collected: AUC = 0.80, 95%CI: 0.75–0.85).ConclusionsDay 3 E2 levels and number of ova collected predict patients who could develop OHSS and may require culdocentesis.

Secondary predictors of ovarian hyperstimulation syndrome development

In the treatment of infertility by the method of fertilization in vitro , such a serious complication as ovarian hyperstimulation syndrome (OHSS) can occur. Primary predictors of OHSS development are widely used in practice while selecting controlled ovarian stimulation patterns. The identification and evaluation of secondary predictors of OHSS development is relevant. Aim. To identify and evaluate secondary predictors of OHSS in women at high risk of OHSS. Materials and methods. The study included 240 women at high risk of developing ovarian hyperstimulation syndrome, 63 of these women subsequently developed ovarian hyperstimulation syndrome, and 177 did not. To identify secondary predictors, a number of preovulatory follicles and oocytes was evaluated, estradiol levels, vascular endothelial growth factor (VEGF) and interleukin‑6 (IL‑6) were defined in the blood serum and follicular fluid. Results . Compared to women without OHSS, there was a statistically significant increase in the number of preovulatory follicles, oocytes, estradiol, VEGF, IL‑6 in the blood serum and follicular fluid in OHSS patients. There was a direct correlation between the serum and follicular fluid levels of estradiol (r s = 0.85; 95 % CI 0.80–0.89; P < 0.001), VEGF (r s = 0.76; 95 % CI 0.69–0.81; P < 0.001) and IL‑6 (r s = 0.67; 95 % CI 0.58–0.74; P < 0.001). Secondary predictors of OHSS was the number of preovulatory follicles ≥30 for two ovary (sensitivity – 46.0 %, specificity – 91.0 %), the number of oocytes ≥19 (sensitivity – 87.3 %, specificity – 97.7 %), serum estradiol levels ≥4800 pg/ml (sensitivity – 74.6 %, specificity – 96.6 %) and estradiol in follicular fluid – ≥725000 pg/ml (sensitivity – 98.4 %, specificity – 97.7 %), serum VEGF ≥ 30 pg/ml (sensitivity – 76.2 %, specificity – 98.3 %) and VEGF in follicular fluid ≥500 pg/ml (sensitivity – 87.3 %, specificity – 97.2 %), IL‑6 in serum ≥4 pg/ml (sensitivity – 65.1 %, specificity – 98.9 %) and IL‑6 in follicular fluid ≥8.5 pg/ml (sensitivity – 90.5 %, specificity – 98.3 %), respectively. Conclusions. The predictors of OHSS should be taken into account to reduce the risk of its development. In identifying secondary predictors of OHSS development, it is necessary to use preventive measures consisting in discontinuation of luteal phase support, vitrification of all embryos and their transfer in subsequent thawed cycles.

Prediction of severe ovarian hyperstimulation syndrome in women undergoing in vitro fertilization using day 3 estradiol levels, collected ova, and the number of follicles

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening iatrogenic condition that can occur during in vitro fertilization (IVF). The worst outcome is hydrothorax, hypovolemia, higher risk of deep venous thrombosis and oliguria. With severe OHSS patients are required to postpone embryo transfer for an undetermined amount of time. Predicting which patients are a high risk of developing OHSS is mainly based on serum estradiol (E2) levels, but other factors, such as female age, BMI, ovarian volume, antral follicle count (AFC), and polycystic ovary syndrome, are speculated to be predictive. Here, we aimed to determine if E2 levels at Day 3 and its fold change at day ten as well as antral follicle count and ova collected are predictive factors for severe OHSS. Retrospective case-control study. Patient chart review was performed between January 2008 and December 2017 at Ingenes in Mexico City. Three hundred twenty-seven women were selected. E2 >3000 ng/L usually on the last day of stimulation (day 10 with three 18 mm-follicles) was defined as OHSS (n=151). Culdocentesis was performed on a patient when upon clinical assessment patient presented features such as nausea, vomiting, oral intolerance and ascites identified by endovaginal ultrasound and abdominal ultrasound (renal and hepatic areas with visible ascites) that do not respond to conservative management (n=55 severe OHSS). Predictability was evaluated by measuring the area under the receiver-operating characteristic (AUC). Differences between groups were determined by t-test. The OHSS positive group, when compared to the non-OHSS group, was higher with respect to E2 Day 3 levels (150±230 v 250±177 ng/L), E2 fold change (20.1±23.8 v 32.2±29.1), AFC (11.6±8.3 v 18.2±9.1), and Ova collected (10.1±6.4, 21.1±9.0, p<0.001). E2 Day 3 levels (AUC=0.76, 95%CI: 0.71-0.82), E2 fold change (AUC=0.71, 95%CI: 0.65-0.77), AFC (AUC=0.75, 95%CI: 0.70-0.81), and Ova collected (AUC=0.85, 95%CI: 0.81-0.89) were predictive of OHSS. For Culdocentesis, E2 Day 3 levels (190±221 v 232±158 ng/L) were not different between the subjects who received culdocentesis, whereas the E2 fold change (24.5±26.6 v 32.9±28.8, p=0.038), AFC (13.7±9.0 v 19.8±8.9, p<0.001), and Ova collected (13.7±8.9, 23.3±8.1, p<0.001) were higher. Interestingly, all variables were predictive of subjects who would qualify for culdocentesis (E2 Day 3 levels: AUC=0.63, 95%CI: 0.55-0.70; E2 fold change: AUC=0.63, 95%CI: 0.55-0.71; AFC: AUC=0.74, 95%CI: 0.68-0.80; and Ova collected: AUC=0.80, 95%CI: 0.75-0.85). Here, we demonstrate the E2 levels, as well as the ova production parameters, are indicators of IVF patients who could develop severe OHSS and may require culdocentesis.

A Second Dose of GnRHa in Combination with Luteal GnRH Antagonist May Eliminate Ovarian Hyperstimulation Syndrome in Women with ≥30 Follicles Measuring ≥11 mm in Diameter on Trigger Day and/or Pre-trigger Peak Estradiol Exceeding 10 000 pg/mL.

This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome (OHSS), characterized by more than 30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL, which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist (GnRHa) trigger and freeze-all policy that previously have been reported. All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards. The in vitro fertilization (IVF) outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS. Moreover, patients' symptoms, reproductive hormone levels and ultrasound findings were improved significantly. This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS, especially for the patients characterized by ≤30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL. Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.

Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial

The purpose of this study was to evaluate the effect of two doses of D-chiro-inositol (DCI) in combination with Myo-inositol (MYO) in women with PCOS undergoing ICSI. This was a multicenter controlled, randomized, double-blind parallel group study with two MYO-DCI formulations for 12 weeks. The study group (SG) was administered 550 mg of MYO + 150 mg of DCI twice daily; the control group (CG) was administered 550 mg of MYO + 13.8 mg of DCI twice daily. The participants comprised 60 women with PCOS undergoing ICSI. At baseline, no differences were found between the two groups regarding age, BMI, HOMA-IR or testosterone levels. The pregnancy and live birth rates were significantly higher in the SG than in the CG (65.5 vs. 25.9 and 55.2 vs. 14.8, respectively) [risk ratio (RR) = 0.4; 95%CI (0.2, 0.79); p = .003 and RR = 0.27; 95%CI (0.10, 0.70); p = .002 respectively]. The risk of ovarian hyperstimulation syndrome (OHSS) was lower in the SG (3.44 vs. 18.5%, p = .07). The combination of MYO-DCI at high doses of DCI improves the pregnancy rates and reduces the risk of OHSS in women with PCOS undergoing ICSI.

Effectiveness of acupuncture in women with polycystic ovarian syndrome undergoing in vitro fertilisation or intracytoplasmic sperm injection: a systematic review and meta-analysis.

The aim of this systematic review was to assess the evidence from randomised controlled trials (RCTs) on the efficacy, effectiveness and safety of acupuncture in women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). We searched a total of 15 databases through October 2015. The participants were women with PCOS (diagnosed using the Rotterdam criteria) undergoing IVF or ICSI. Eligible trials were those with intervention groups receiving manual acupuncture (MA) or electroacupuncture (EA), and control groups receiving sham acupuncture, no treatment or other treatments. Outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), ongoing pregnancy rate (OPR) and incidence of ovarian hyperstimulation syndrome (OHSS) and adverse events (AEs). For statistical pooling, the risk ratio (RR) and its 95% (confidence interval) CI was calculated using a random effects model. Four RCTs including 430 participants were selected. All trials compared acupuncture (MA/EA) against no treatment. Acupuncture significantly increased the CPR (RR 1.33, 95% CI 1.03 to 1.71) and OPR (RR 2.03, 95% CI 1.08 to 3.81) and decreased the risk of OHSS (RR 0.63, 95% CI 0.42 to 0.94); however, there was no significant difference in the LBR (RR 1.61, 95% CI 0.73 to 3.58). None of the RCTs reported on AEs. Acupuncture may increase the CPR and OPR and decrease the risk of OHSS in women with PCOS undergoing IVF or ICSI. Further studies are needed to confirm the efficacy and safety of acupuncture as an adjunct to assisted reproductive technology in this particular population.