Involvement of single nucleotide polymorphisms in ovarian poor response.

PURPOSE: Unpredictability in acquiring an adequate number of high-quality oocytes following ovarian stimulation is one of the major complications in controlled ovarian hyperstimulation (COH). Genetic predispositions of variations could alter the immunological profiles and consequently be implicated in the variability of ovarian response to the stimulation. DESIGN: Uncovering the influence of variations in AMHR2, LHCGR, MTHFR, PGR, and SERPINE1 genes with ovarian response to gonadotrophin stimulation in COH of infertile women. METHODS: Blood samples of the women with a good ovarian response (GOR) or with a poor ovarian response (POR) were collected. Genomic DNA was extracted, and gene variations were genotyped by TaqMan SNP Genotyping Assays using primer-probe sets or real-time PCR Kit. RESULTS: Except for PGR (rs10895068), allele distributions demonstrate that the majority of POR patients carried minor alleles of AMHR2 (rs2002555, G-allele), LHCGR (rs2293275, G-allele), MTHFR (rs1801131, C-allele, and rs1801133, T-allele), and SERPINE1 (rs1799889, 4G allele) genes compared to the GOR. Similarly, genotypes with a minor allele in AMHR2, LHCGR, MTHFR, and SERPINE1 genes had a higher prevalence among POR patients with the polymorphic genotypes. However, further genotype stratification indicated that the minor alleles of these genes are not associated with poor response. Multivariate logistic analysis of clinical-demographic factors and polymorphic genotypes demonstrated a correlation between FSH levels and polymorphic genotypes of SERPINE1 in poor response status. CONCLUSIONS: Despite a higher prevalence of AMHR2, LHCGR, MTHFR, and SERPINE1 variations in the patients with poor ovarian response, it seems that these variations are not associated with the ovarian response.

Transient receptor potential melastatin 2 ion channel activity in ovarian hyperstimulation syndrome physiopathology

Background/aim: Ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation with increased vascular endothelial growth factor (VEGF) and vascular permeability in the ovarian tissue. Transient receptor potential melastatin 2 (TRPM2) is known to be associated with angiogenesis and vascular permeability. In this experimental study, we aimed to investigate the activity of TRPM2 in the development of OHSS. Materials and methods: Fourteen immature female rats were divided into two groups. Group 1 was the control group, and Group 2 was the OHSS group that was exposed to 10 IU of subcutaneous application of FSH for four days and 30 IU of human chorionic gonadotropin (hCG) on the 5th day. At the end of the experiment, the ovaries were removed. The right ovarian tissues were stored in 10% formol for histopathological and immunohistochemical examination. The left ovarian tissues were stored at ­80 °C for biochemical examinations. VEGF, tumor necrosis factor-alpha (TNF­α) and malondialdehyde (MDA) levels were measured in the ovarian tissue. Congestion, edema, apoptosis and TRPM2 immunoreactivity were evaluated. Results: There was a significant increase in ovarian weight in the OHSS group compared to the control group. There was a significant increase in congestion, edema, apoptosis and TRPM2 immunoreactivity in the OHSS group. A significant increase in tissue levels of VEGF, TNF­α and MDA was also found in the OHSS group compared to the control group. Conclusion: As a result of our experiment, it was found that increased TRPM2 immunoreactivity on hyperstimulated rat ovary may be the reason or result of edema and congestion. Further studies are needed to discuss our results.

Insulin Resistance and Free Androgen as Predictors for Ovarian Hyperstimulation Syndrome in Non-PCOS Women.

We evaluated the effect of insulin resistance and free androgen index (FAI) in non-PCOS (polycystic ovary syndrome) infertile women following controlled ovarian hyperstimulation. A prospective study was done on 144 infertile non-PCOS women with regular menstrual cycle. At first, insulin resistance (IR), free androgen index (FAI), PCOM (polycystic ovary morphology), AFC (antral follicle count), and AMH (anti-Müllerian hormone) were assessed. The patients underwent assisted reproductive technology (ART), and then preovulatory follicles and oocytes retrieved were recorded. The variables of the study were compared between two groups of patients with ovarian hyperstimulation syndrome (OHSS) (n=66) and non-OHSS patients (n=78). Of the 9 variables: BMI, HOMA-IR, FAI, AFC, AMH, PCOM, and preovulatory follicles were risk factors, while the age and retrieved oocytes were not. The 7 variables that showed significance in the univariate analyses were determined as independent variables included in the multivariable logistic regression analysis, as a result, a total of 5 risk factors, BMI, HOMA-IR, FAI, PCOM, and preovulatory follicles entered the equation. The maximum contribution was HOMA-IR followed by PCOM, FAI, preovulatory follicles and BMI. Patients with OHSS had higher chance to have ovaries with polycystic morphology (74%), about three times more than patients who did not develop OHSS (29%) (p<0.001). The best cut-points for IR, FAI, AFC, AMH, and preovulatry follicles were 2.36, 3.9, 8, 3.3 ng/ml, and 10, respectively. Patients with a higher value of BMI, FAI, HOMA-IR, and preovulatory follicles and the presence of PCOM are more likely to develop OHSS, which are not confined to PCOS patients.

Ovarian hyperstimulation syndrome: A review for emergency clinicians.

INTRODUCTION: A great deal of literature has recently evaluated the prevention and management of ovarian hyperstimulation syndrome (OHSS) in the outpatient setting, but there remains a dearth of research evaluating OHSS in the emergency department (ED) and its management. OBJECTIVE: This narrative review evaluates the underlying pathophysiology and clinical manifestations of OHSS and discusses approaches to patient care in the ED based on current literature. DISCUSSION: OHSS is an iatrogenic complication caused by an excessive response to controlled ovarian stimulation during assisted reproductive cycles (ART). OHSS complicates up to 30% of ART cycles, and many of these patients seek initial care in the ED. Risk factors for the development of OHSS include age < 35, history of polycystic ovarian syndrome or previous OHSS, and pregnancy. Emergency physicians will be faced with several complications including ascites, abdominal compartment syndrome, renal dysfunction, acute respiratory distress syndrome, thromboembolic disease, and hemodynamic instability. Critical patients should be evaluated in the resuscitation bay, and consultation with the primary obstetrics/gynecology team is needed, which improves patient outcomes. This review provides several guiding principles for management of OHSS and associated complications. CONCLUSIONS: OHSS occurs in up to 30% of IVF cycles and carries a high morbidity. Effective care of the OHSS patient begins with early diagnosis while evaluating for other diseases and complications. Understanding these complications and an approach to the management of OHSS is essential to optimizing patient care.

Rare genetic variants potentially involved in ovarian hyperstimulation syndrome.

PURPOSE: We aim to investigate whether there is a genetic predisposition in women who developed ovarian hyperstimulation syndrome (OHSS) after GnRH antagonist protocol with GnRH agonist trigger and freeze-all approach. METHODS: Four patients with OHSS after GnRH agonist trigger and freeze-all approach were gathered from the worldwide patient population. These patients were analyzed through Whole Exome Sequencing. In this study known causes of OHSS were investigated and new causes present in at least two individuals were searched for. RESULTS: In the first part of the study, we evaluated the presence of mutations in genes already known to be involved in OHSS. In PGR and TP53, heterozygous alterations were detected. PGR is predicted to be involved in progesterone resistance with a recessive inheritance pattern and is, therefore, not considered as being causal. The consequences of the variant detected in TP53 currently remain unknown. In part 2 of the study, we assessed the clinical significance of variants in genes previously not linked to OHSS. We especially focused on genes with variants present in ≥ 2 patients. Two patients have variants in the FLT4 gene. Mutations in this gene are linked to hereditary lymphedema, but no link to OHSS has been described. CONCLUSIONS: Defining a genetic predisposition for OHSS is essential in view of prevention. In this study, a potential link between the FLT4 gene and OHSS has been suggested. Future functional studies are essential to define a more precise involvement of the detected variants in the development of OHSS.

Ovarian Hyperstimulation Syndrome as a Growing Diagnostic Problem in Emergency Department Settings: A Case Report.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a common complication of an in-vitro fertilization (IVF) procedure, which is usually clinically insignificant. However, without monitoring, it can progress into a life-threatening condition. With the increasing popularity of IVF technology, patients with OHSS may begin visiting emergency departments (EDs) more frequently. CASE REPORT: We report the case of a patient admitted to the ED presenting with severe abdominal pain, cough, and nausea. An ultrasound examination was inconclusive. Computer tomography revealed enlarged ovaries and fluid in the pleural cavities, around the liver and spleen, between the bowel loops, and in the pelvis. This prompted physicians to review the patient's fertility issues. Consequently, the diagnosis of OHSS was made. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When the physician knows that the patient is undergoing IVF, the diagnosis of OHSS can be straightforward; without this information, it can be difficult. Having in mind the growing demand for infertility treatment, we present this case to increase awareness of possible clinical findings and complications of OHSS as a rare consequence of IVF. OHSS diagnosed via ultrasound can reduce the emotional, financial, and health burden of infertile couples and help them to fulfill their procreation plans without unnecessary delay.

Ultrasound and hematological changes during early luteal phase in women at high risk for developing ovarian hyperstimulation syndrome.

OBJECTIVE: To assess ultrasound and hematological changes during the early luteal phase following triggering of final oocyte maturation with human chorionic gonadotropin (hCG) in women at high risk for developing ovarian hyperstimulation syndrome (OHSS). METHODS: This was a retrospective cohort study of 319 women undergoing in-vitro fertilization who were at high risk for OHSS following administration of hCG for the triggering of final oocyte maturation. Patients were treated with a gonadotropin-releasing hormone agonist or antagonist protocol and were monitored for 5 days post-oocyte retrieval (early luteal phase). Severe OHSS was diagnosed in the presence of at least moderate ascites and two or more of the following: maximum ovarian diameter (MOD) > 100 mm, hematocrit (Ht) > 45%, white blood cell count (WBC) > 15 000/mm3 , hydrothorax, dyspnea and oliguria. Outcome measures included change in Ht, ascites grade, WBC and MOD, as well as the association between these changes during the early luteal phase. RESULTS: Ascites grade, Ht and WBC increased significantly (P ≤ 0.001) during the early luteal phase, both in patients who developed and in those who did not develop severe early OHSS. MOD increased significantly (P = 0.001) only in patients who developed severe early OHSS. On multivariable analysis, both time following oocyte retrieval and whether severe early OHSS developed were significantly associated with ascites grade, Ht, WBC and MOD; furthermore, there was also a significant interaction between time and development of severe early OHSS for all four variables (P ≤ 0.001). CONCLUSIONS: In women at high risk of OHSS, ascites grade, Ht and WBC significantly increased with time over the 5-day observation period, in line with the pathophysiology of the syndrome. Our data support the use of MOD in the diagnosis of severe early OHSS, and provide novel evidence for the role of change in Ht as a patient-specific hemoconcentration marker during development of OHSS. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Unilateral pleural effusion as the sole clinical presentation of severe ovarian hyperstimulation syndrome: a systematic review.

The pathophysiology of isolated pleural effusion in ovarian hyperstimulation syndrome (OHSS) is not well defined. The objective of the current review is to delineate the pathophysiology, risk factors, preventive measures, and therapeutic options of isolated pleural effusion in severe OHSS. Major databases were searched until June 2016. Studies evaluating women who presented with pleural effusion as the sole extra-ovarian manifestation of severe OHSS were included. Data were extracted from 24 articles encompassing 30 reported cases. Values were expressed as mean ± SEM. Patients were young (31.5 ± 0.8 years old) and 29.1% of them were diagnosed with polycystic ovary syndrome. All the patients received human chorionic gonadotropin to trigger oocyte maturation. Estradiol level was 3110 ± 330 pg/mL on the day of the ovulatory trigger. Dyspnea was the presenting symptom in 86.6% of the patients. Pleural effusion was predominantly on the right side (80%). Ninety percent of the patients underwent thoracentesis (4332 ± 769 mL): 66.7% exudate and 33.3% transudate. Fluid initially accumulates in the peritoneal cavity then enters the pleural space due to the pressure gradient through the thoracic duct and diaphragmatic defects, which are more common on the right side. The risk factors, prevention, and management, which are also discussed in this review, are similar to those of severe OHSS.

[Pathophysiology and current clinical approach of ovarian hyperstimulation syndrome]. / Az ovarialis hiperstimulációs szindróma kórélettana és korszeru klinikuma.

During assisted reproduction technologies, controlled hyperstimulation of the ovaries occurs. Ovarian hyperstimulation syndrome is an excessive overreaction of the ovaries complicating pharmacological ovulation induction. Rarely other causes, such as the mutation of the follicle-stimulating hormone receptor may also be in the background. Ovarian hyperstimulation syndrome is clinically characterized by a massive ovarian enlargement associated with an acute third-space fluid shift responsible for the development of ascites, and sometimes pleural or pericardial effusion. Associated arterial or venous thromboembolic symptoms are also common. Ovarian hyperstimulation syndrome is an iatrogenic and potentially life-threatening condition in the form of ischemic stroke or circulatory insufficiency of the limbs. Recently some new methods have been developed for the prevention of the disease. The syndrome affects young, healthy patients. It also has an important economic burden due to the absence from work, bed rest, or hospitalization and intensive medical management of more severe cases. Supportive therapy, anticoagulant prophylaxis and close monitoring are the main approach for the syndrome. However, hospitalization or intervention should not be delayed for patients with severe or critical conditions. Orv Hetil. 2018; 159(34): 1390-1398.

Fresh versus frozen-thawed blastocyst transfer in high responders.

OBJECTIVE: This study aimed to investigate and compare the pregnancy and live birth rates in IVF cycles of frozen-thawed embryo transfers and fresh embryo transfers in a group of women with a high risk of Ovarian hyperstimulation syndrome (OHSS). MATERIAL AND METHODS: The study group consisted of 254 women with a high level of response to controlled ovarian hyperstimulation. The patients who received fresh cycle embryo transfers with calcium infusions are referred to as the Fresh Ca+ group, and those without the calcium therapy are called the Fresh Ca- group; and we used correspondingly similar terminology for the Frozen group. RESULTS: We observed no statistically significant differences between the cycles of fresh and frozen-thawed embryo transfers in patients with a high risk of OHSS in terms of implantation, clinical pregnancy, and live birth rates. Furthermore, these implantation, clinical pregnancy and live birth rates were not different in the cycles with or without calcium treatment. There was no statistical difference in the OHSS rates between the fresh and frozen-thawed cycles; although, the OHSS rates were less in the two calcium infusion groups (Fresh Ca+ and Frozen-thawed Ca+) than in the without-calcium group. There was no OHSS development in the subjects of the Frozen-thawed Ca+ group. CONCLUSION: Our study results suggest that fresh and frozen-thawed embryo transfers have similar IVF results in patients with a high risk of OHSS. Calcium infusion is beneficial in preventing OHSS without altering pregnancy rates. Both IVF protocols with calcium infusion can safely be applied in high-responder patients without lowering success rates.

The myths surrounding mild stimulation in vitro fertilization (IVF).

So-called mild controlled ovarian hyperstimulation (mCOH) has in recent years increased in popularity, claiming to be safer and more patient-friendly, while also improving in vitro fertilization (IVF) outcomes. We here challenge the International Society for Mild Approaches in Assisted Reproduction (ISMAAR) definition of mild stimulation, and especially address four fundamental issues, where our review found conventional COH (cCOH) advantageous over mCOH. They are: prevalence of severe ovarian hyperstimulation syndrome (OHSS), oocyte/embryo quality, pregnancy/live birth rates, and cost. We conclude that an objective review of the literature does not support the routine utilization of mCOH in assisted reproduction.

Sequential E2 levels not ovarian maximal diameter estimates were correlated with outcome of cetrotide therapy for management of women at high-risk of ovarian hyperstimulation syndrome: a randomized controlled study.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an important condition with considerable morbidity and a small risk of mortality and most commonly results as an iatrogenic condition following follicular stimulation of the ovaries. We aimed to evaluate safety and efficacy of 3-day cetrotide therapy started on day of oocyte retrieval (Day-0) in women at high-risk for development of ovarian hyperstimulation syndrome (OHSS) after GnRH agonist induction protocol. METHODS: Forty-eight women fulfilling inclusion criteria underwent ultrasound scanning for maximal ovarian diameter (MOD) estimation and ascites grading. Patients underwent embryo freezing, but the study group received 3-day Cetrotide sc injection (0.25 mg/day) started on Day-0. Serum E2, pain scores and MOD were checked daily. Hematocrite value (Ht%), total leucocytic count (TLC), gastrointestinal (GI) manifestations and ascites grading were re-evaluated on Day-3, 6 and 8. RESULTS: Sequential serum E2 levels decreased significantly in both groups with significantly lower levels in the study group. Sequential MOD estimates showed non-significant difference between the two groups and versus Day-0 estimates. On Day-2, pain scores showed progressive significant decrease compared to Day-0 scores in both groups with significantly lower scores in the study group. On Day-3; four control patients still had vomiting and by Day-6, 6 of the control patients still had GI manifestations with significant difference versus the study group. Compared to Day-0 estimates, Ht% and TLC were significantly lower on Day-3, 6 and 8 in the study group, but only on Day-8 in the control group. Day-3 and Day-8 ascites grading in both groups was significantly lower compared to respective Day-0 grading with significant difference in favor of the study group. Six patients required hospitalization, but without mortalities. Day-3 E2 levels in the study group showed positive significant correlation with clinical and other laboratory data and ascites grading, while the correlation was non-significant with MOD. CONCLUSION: The 3-day cetrotide therapy starting after oocyte retrieval with embryo transfer freezing could be an appropriate management policy for women received GnHR-agonist induction protocol and were at high-risk for OHSS. Sequential E2 serum levels could predict outcome more perfectly than sequential MOD estimates. TRIAL REGISTRATION: Trial registration ( clinicaltrial.gov registration) NCT02823080 (retrospective) Initial Release 21-6-2016 Last Release 3-1-2017 Unique Protocol ID: Benha U Secondary IDs: kmsalama.

Severe ovarian hyperstimulation syndrome after combined GnRH-agonist and low-dose human chorionic gonadotropin trigger in a patient with a single kidney.

Ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone agonist (GnRH-a) trigger is rare. Here, we report a case of severe OHSS after combined GnRH-a and low-dose human chorionic gonadotropin (hCG) trigger in a patient with a single kidney. The patient is a 32-year-old women with a two-year history of infertility. The patient's history was significant for a single kidney, that is, she had donated a kidney to a family member three years ago. The patient underwent controlled ovarian stimulation (COS) for in vitro fertilization (IVF) and received a combined 2 mg GnRH-a and 1500 IU hCG ovulatory trigger. Estradiol (E2) levels on the day of and after the trigger were 3800 pg/mL and 4001 pg/mL, respectively. Four days after the trigger, the patient began experiencing nausea, abdominal distention and dyspnea, and her blood testing revealed hemoconcentration (hemoglobin: 16.9 g/dL; hematocrit: 51.0%) and an elevated creatinine level (1.16 mg/dL). Fresh embryo transfer was deferred. The patient was admitted to the hospital for fluid monitoring and prophylactic anticoagulation. Following inpatient management, her hemoglobin, hematocrit and creatinine levels normalized. The current report highlights that the systemic effects of OHSS can be accentuated in patients with preexisting renal disease or a single kidney.

Outcome of gestational surrogacy according to IVF protocol.

PURPOSE: Surrogacy remains the only option for having a biologic child for a unique population of women with severe medical conditions. However, no study has looked at surrogacy outcome as a result of the type of ovarian stimulation of the intended mother [controlled ovarian stimulation (COH), modified natural cycle (MNC), and in vitro maturation (IVM)] for oocyte retrieval. METHODS: This is a retrospective study, including all intended mothers and gestational carriers in a tertiary, university affiliated, medical center, from 1998 to 2016. RESULTS: Fifty-two women underwent 252 oocyte retrieval cycles. The pregnancy outcome of 212 embryo transfer cycles (64 gestational carriers) was reviewed according to the origin of the embryo. The number of retrieved oocytes was significantly higher following COH (n = 132) compared with IVM (n = 58) and MNC cycles (n = 62) (p = 0.013 and p < 0.0001, respectively). Pregnancy rates for embryos transferred according to each protocol were similar. All pregnancies that ended in live births when oocytes from IVM cycles were used derived from transfers of retrieved mature and mixed mature and immature oocytes. Pregnancies that involved embryos derived solely from immature oocytes that further matured in vitro and were transferred to gestational carriers were unsuccessful. CONCLUSIONS: MNC protocol is a good option to achieve pregnancy for intended mothers using gestational surrogacy who have contraindications to COH. The yield of IVM cycles in which immature oocytes are retrieved is inconclusive.

The cumulative dose of gonadotropins used for controlled ovarian stimulation does not influence the odds of embryonic aneuploidy in patients with normal ovarian response.

OBJECTIVE: Controlled ovarian hyperstimulation (COH) promotes multifollicular growth, increasing the chance of obtaining euploid embryos that will successfully implant. Whether aneuploidy is increased from COH with exogenous gonadotropins interfering with natural selection of dominant follicles is a concern. This study evaluates the association between gonadotropin exposure and aneuploidy. METHODS: This is a retrospective cohort study of 828 patients that underwent 1122 IVF cycles involving controlled ovarian stimulation and trophectoderm biopsy for preimplantation genetic screening (PGS), from 2010 to 2015. Polymerase chain reaction (PCR) was used to assess aneuploidy. Kruskal-Wallis tests and logistic regression with generalized estimating equations (GEEs) were used for data analysis. RESULTS: Overall, after controlling for patient age, ovarian reserve, stimulation protocol, days of stimulation, and diagnoses, there was no significant association between cumulative gonadotropin (GND) dose and the odds of aneuploidy (adjusted OR = 1.049, p = 0.232). Similarly, in cycles where patients did not require COH beyond cycle day 12, there was no significant association between cumulative gonadotropin dose and the odds of aneuploidy (adjusted OR = 0.909, p = 0.148). However, in cases where patients were stimulated past cycle day 12, there was a significant increase in the odds of aneuploidy (adjusted OR = 1.20, 95% CI 1.125-1.282, p < 0.0001) with increasing cumulative gonadotropin dose, with a small effect size (Cohen's d = 0.10, 95% CI 0.08-0.12). In this cohort, there was a 16.4% increase in the odds of aneuploidy for each 1000-u increase in cumulative GND exposure (adjusted OR = 1.164, p = 0.002). When the analysis was restricted to low responders (peak estradiol <500 pg/mL or <4 mature follicles achieved; there was no significant association between gonadotropin dose and aneuploidy (adjusted OR = 1.12, 95% CI 0.982-1.28, p = 0.09), regardless of the duration of COH required to reach vaginal oocyte retrieval. CONCLUSION: The degree of exposure to exogenous gonadotropins did not significantly modify the likelihood of aneuploidy in patients with a normal ovarian response to stimulation (not requiring COH beyond cycle day 12). Patients requiring prolonged COH were demonstrated to have elevated odds of aneuploidy with increasing cumulative gonadotropin dose. This finding may reflect an increased tendency towards oocyte and embryonic aneuploidy in patients with a diminished response to gonadotropin stimulation.

Association between peak estradiol levels and ovarian torsion among symptomatic patients receiving gonadotropin treatment.

PURPOSE: Ovarian torsion is a surgical emergency that can be clinically challenging to diagnose. Patients who have received assisted reproductive technologies (ART) are a subset of women with an increased risk for torsion. As the ART population continues to increase, there is a need to delineate risk factors for the development of ovarian torsion in this unique population. A pilot study was performed to determine the proportion of patients with suspected ovarian torsion who have received ART and to identify possible diagnostic biomarkers for ovarian torsion among these patients. METHODS: A single institution retrospective cohort study of patients taken to surgery for suspected ovarian torsion over a 5-year period. RESULTS: During the study period, 171 patients were taken to surgery for suspected ovarian torsion. Patients receiving ART constituted 19 (11%) of these patients. Among the 19 fertility treatment patients, 16 had received treatment with gonadotropins, 10 of which had surgically confirmed ovarian torsion. These ten patients had higher preoperative peak estradiol levels (3122 versus 1875 pg/mL, p = 0.05) and a larger ovarian diameter (9.7 versus 7.6 cm, p = 0.05) than the six patients receiving gonadotropins found to not have ovarian torsion. CONCLUSIONS: These results suggest infertility treatment using gonadotropins for ovarian hyperstimulation may be an independent risk factor for ovarian torsion as suggested by the disproportionate number of such individuals represented in the study population (9% of all patients, 84% of fertility patients). Additionally, among women taking gonadotropins, an association exists between peak estradiol levels, ovarian diameter, and risk for ovarian torsion.

Combined GnRH-agonist and human chorionic gonadotropin trigger improves ICSI cycle outcomes in patients with history of poor fertilization.

PURPOSE: The purpose of this study was to investigate the utility of a combined GnRH-agonist (GnRH-a) and human chorionic gonadotropin (hCG) trigger in improving ICSI cycle outcomes in patients with poor fertilization history after standard hCG trigger in prior ICSI cycles. METHODS: Retrospective cohort study. Patients with a fertilization rate of <20% in at least two prior ICSI cycles who subsequently underwent another ICSI cycle with hCG trigger were compared to those who underwent another ICSI cycle with a combined GnRH-a and hCG trigger. Oocyte maturity, fertilization, clinical pregnancy, and live birth rates were compared. A multiple linear regression model was used to explore the association between combined GnRH-a and hCG trigger (vs hCG trigger alone) and fertilization rate. RESULTS: A total of 427 patients with mean age of 37.3 ± 1.94 years and mean baseline fertilization rate of 17.9 ± 2.03% were included, of which 318 (74.5%) and 109 (25.5%) patients underwent a subsequent ICSI cycle with hCG and combined GnRH-a and hCG trigger, respectively. The baseline parameters of the male and female partner were similar. The mean fertilization rate in the combined trigger group was 16.4% (95% CI: 7.58-25.2%) higher than the hCG trigger group, even after adjustment for confounders. Patients in the combined trigger group had higher oocyte maturity (82.1 vs 69.8%), higher clinical pregnancy (27.5 vs 5.67%), and higher live birth rates (20.2 vs 3.46%) compared to the hCG trigger group. CONCLUSIONS: Combined GnRH-a and hCG trigger in ICSI cycles increase oocyte maturity, fertilization, clinical pregnancy, and live birth rates in patients with a history of poor fertilization after standard hCG trigger alone.

Effect of body mass index on the outcomes of controlled ovarian hyperstimulation in Chinese women with polycystic ovary syndrome: a multicenter, prospective, observational study.

PURPOSE: The purpose of the present study is to explore the influence of body mass index (BMI) on outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) techniques in Chinese women with polycystic ovary syndrome (PCOS). METHODS: This was a multicenter, prospective, observational study that enrolled 800 subjects with PCOS from nine hospitals in China. Patients were categorized according to BMI categories: underweight, <18.5 kg/m2; normal, 19-23.9 kg/m2; overweight, 24-27.9 kg/m2; and obese, ≥28 kg/m2. Total recombinant follicle-stimulating hormone (rFSH) dose used, estradiol, and progesterone levels on human chorionic gonadotropin (hCG) day; implantation rate; and biochemical, clinical, and ongoing pregnancy rates were compared among BMI categories. Hormone levels (estradiol, follicle-stimulating hormone (FSH), LH, testosterone, and progesterone) were measured using electrochemiluminescence assays. RESULTS: Among the 774 subjects, 27.3 % were overweight and 8.1 % were obese. The rFSH dose used differed significantly among BMI categories (P < 0.001). The implantation rate was lower in obese subjects than that in normal-weight subjects (25.3 vs 45.7 %). Clinical pregnancy rate per transfer differed among BMI categories (P = 0.033), but there was no difference for biochemical (P = 0.327) and ongoing (P = 0.084) pregnancy rates. The miscarriage rate was similar among BMI categories. CONCLUSIONS: More than one third of Chinese women with PCOS undergoing IVF/ICSI are overweight or obese. Elevated BMI is associated with reduced clinical pregnancy rate but similar ongoing pregnancy rates, suggesting that BMI has little impact on IVF outcomes.

Ovarian hyperstimulation syndrome following GnRH agonist trigger-think ectopic.

PURPOSE: This study aims to report a case of ovarian hyperstimulation syndrome (OHSS) following GnRH agonist trigger for final follicular maturation. METHODS: This study is a retrospective chart review. RESULTS: We report the first case of OHSS following GnRH agonist trigger for final follicular maturation and freeze-all, masking extrauterine pregnancy (EUP). The present case report elucidates the feasibility of stimulating and recruiting ovarian follicles yielding mature oocytes during early pregnancy and the ability of GnRH agonist to trigger final follicular maturation during pregnancy, in the presence of high progesterone and hCG levels. CONCLUSIONS: Since OHSS almost always develops after hCG administration or in early pregnancy, its occurrence following GnRH agonist trigger should alert physician to search for either an inadvertent administration of exogenous hCG, or the endogenous secretion of hCG by pregnancy, e.g. EUP, or as part of a paraneoplastic syndrome.

Use of Point-of-Care Ultrasound for the Diagnosis of Ovarian Hyperstimulation Syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) occurs when ovaries are overstimulated and enlarged due to fertility treatments resulting in a shift of serum from the intravascular space to the third space, mainly the abdominal cavity. It is the most serious complication of ovarian hyperstimulation for assisted reproduction. CASE REPORT: We present the case of a 40-year-old woman who presented with abdominal bloating and nausea 2 weeks after undergoing in vitro fertilization (IVF); she was diagnosed by an outside radiology ultrasound as having a ruptured ovarian cyst. A point-of-care emergency ultrasound performed by the emergency physician made the diagnosis of ovarian hyperstimulation syndrome. This led to more expedient management and obstetrical consultation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Abdominal bloating and nausea are common presenting complaints in pregnant women. OHSS is a rare but potentially fatal complication of IVF. Recognition and early diagnosis by the emergency physician can lead to appropriate intervention and consultation.