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.

Impact of changing the ovarian hyperstimulation protocol in the sequental cycle on ICSI outcomes in the same patient population.

AIM: Whether to use the same ovarian stimulation protocol or change it after a failed in vitro fertilization cycle is still a controversial issue. In this study we aimed to investigate the effect of changing the stimulation protocol in the sequental cycle of the same patient population on intracytoplasmic sperm injection (ICSI) outcomes. METHODS: This retrospective study included two sequental fresh ICSI cycles of 941 infertile women attended in a period of one year. Group A was composed of patients who failed to have clinical pregnancy with a GnRH agonist and group B was composed of patients who failed to have clinical pregnancy with a GnRH antagonist protocol cycle. In both groups the study group was composed of patients whose stimulation protocol was changed in the sequential cycle and the control group was composed of patients who proceeded with the same stimulation protocol. The clinical pregnancy and live birth rates were primary outcomes. RESULTS: In group A, the clinical pregnancy rates were comparable between the study and the control groups, but the live birth rate was higher in the study group (p=0.03). In group B, there was no difference in terms of clinical pregnancy and live birth rates between the study and control groups (p=0.740 and p=0.842 respectively). CONCLUSIONS: Changing the ovarian stimulation protocol after a failed ICSI cycle downregulated with a GnRH agonist increased the live birth rate. After a failed cycle stimulated with a GnRH antagonist protocol, protocol change did not have any impact on the clinical pregnancy and live birth rates.

[Sudden exercise dyspnea in a young woman - an interdisciplinary case in the emergency room]. / Plötzliche Belastungsdyspnoe bei einer jungen Frau ­ internistisch-gynäkologisches Grenzgebiet in der Notaufnahme.

HISTORY: A 39-year-old woman with suddenly occurring exercise dyspnea is admitted under the suspicion of pulmonary embolism. In medical history, she mentions a recently completed fertility treatment. FINDINGS AND DIAGNOSIS: Clinically, the patient is in good condition. D-dimers and hCG are markedly elevated. Sonography reveals pronounced ascites, a large right-sided pleural effusion and multicystic, clearly enlarged ovaries. In conjunction with medical history and confirmed by the gynecologists, the diagnosis of ovarian hyperstimulation syndrome (OHSS) is made, classified as grade II-III (moderate to severe). THERAPY AND COURSE: Thrombembolic prophylaxis with Certoparin 3000 IU/d is established as sole therapy. The course of the disease is self-limited. CONCLUSION: OHSS is primarily a gynaecological condition, but physicians may encounter it with exercise dyspnea or abdominal pain as presenting symptoms. Symptoms can be treated well at an early stage, and severe courses can usually be prevented. In this case, clinical history and sonography could disprove the initially suspected diagnosis of pulmonary embolism.

Differential impact of controlled ovarian hyperstimulation on live birth rate in fresh versus frozen embryo transfer cycles: a Society for Assisted Reproductive Technology Clinic Outcome System study.

OBJECTIVE: To study the impact of both controlled ovarian hyperstimulation (COH) length and total gonadotropin (GN) dose individually and in concert on live birth rates (LBR) in both fresh and freeze-all in vitro fertilization embryo transfer (IVF-ET) cycles. DESIGN: Historical cohort study. SETTING: Not applicable. PATIENT(S): The U.S. national database from the Society of Assisted Reproductive Technology Clinic Outcome Reporting System from 2014 to 2015 was used to identify patients undergoing autologous GN stimulation IVF cycles with the use of GnRH antagonist-based suppression protocols where a single embryo transfer was performed as part of a fresh IVF-ET cycle (fresh, n = 14,866) or the first frozen embryo transfer after a freeze-all cycle (frozen, n = 2,964), and not including preimplantation genetic testing cycles. The patients' demographic and cycle characteristics, duration of COH, total GN dose, and pregnancy outcomes were extracted. Binomial regression models estimated trend and relative risk of live birth with respect to days of stimulation and total GN dose singularly, and after adjustment for a priori confounders including age, parity, body mass index, diagnosis, and maximum follicle-stimulating hormone in both fresh and frozen embryo transfer cycles. Both days of stimulation and total GN dose were then added to the multivariate model to show whether they were independently associated with LBR. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Live birth rate. RESULTS: In both fresh and frozen cycles, length of COH was significantly associated with total GN dose. On univariate analysis, LBR decreased significantly with increasing length of stimulation and increasing total GN dose in both fresh and frozen cycles. On multivariable analysis including both days of stimulation and total GN dose, days of stimulation was no longer significantly correlated with LBR, whereas total GN dose remained significantly correlated with LBR in fresh cycles only. When total GN doses ranging from <2,000 IU through 5,000 IU to >5,000 IU were compared, a significant improvement in live birth rate was noted with lower total GN doses. Specifically, GN doses <2,000 IU had a 27% higher rate of live birth compared with GN dose >5,000 IU. For GN dose groups up to 4,000 IU, the estimated effect on LBR was similar. There was a marginal improvement (13%) in LBR with GN doses of 4,000 IU to 5,000 IU compared with >5,000 IU. When the multivariate model was applied to the frozen cycles, neither total GN dose nor days of stimulation was significantly associated with LBR. CONCLUSIONS: High total GN dose but not prolonged COH is associated with decreasing LBRs in fresh cycles, whereas neither factor significantly affects LBR in frozen cycles. Consideration should be given to minimizing the total GN dose when possible in fresh autologous cycles, either by decreasing the daily dose or by limiting the length of stimulation to improve LBRs. In freeze-all cycles, the use of higher GN doses does not seem to adversely affect the LBR of the first frozen embryo transfer. High total GN dose likely exerts a negative impact on the endometrium and/or oocyte/embryo unrelated to the length of stimulation. The differential effect of total GN dose on LBR in fresh and frozen cycles may imply a greater impact exerted on the endometrium rather than the oocyte.

Ovarian hyperstimulation syndrome after assisted reproductive technologies: trends, predictors, and pregnancy outcomes.

OBJECTIVES: To assess trends, predictors, and perinatal outcomes of ovarian hyperstimulation syndrome (OHSS) associated with in vitro fertilization (IVF) cycles in the United States. DESIGN: Retrospective cohort study using National Assisted Reproductive Technology Surveillance System (NASS) data. SETTING: Not applicable. PATIENT(S): Fresh autologous and embryo-banking cycles performed from 2000 to 2015. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): OHSS, first-trimester loss, second-trimester loss, stillbirth, low birth weight, and preterm delivery. RESULT(S): The proportion of IVF cycles complicated by OHSS increased from 10.0 to 14.3 cases per 1,000 from 2000 to 2006, and decreased to 5.3 per 1,000 from 2006 to 2015. The risk of OHSS was highest for cycles with more than 30 oocytes retrieved (adjusted risk ratio [aRR] 3.85). OHSS was associated with a diagnosis of ovulatory disorder (aRR 2.61), tubal factor (aRR 1.14), uterine factor (aRR 1.17) and cycles resulting in pregnancy (aRR 3.12). In singleton pregnancies, OHSS was associated with increased risk of low birth weight (aRR 1.29) and preterm delivery (aRR 1.32). In twin pregnancies, OHSS was associated with an increased risk of second-trimester loss (aRR 1.81), low birth weight (aRR 1.06), and preterm delivery (aRR 1.16). CONCLUSION(S): Modifiable predictive factors for OHSS include number of oocytes retrieved, pregnancy following fresh embryo transfer, and the type of medication used for pituitary suppression during controlled ovarian hyperstimulation. Patients affected by OHSS had a higher risk of preterm delivery and low birth weight. Clinicians should take measures to reduce the risk of OHSS whenever possible.

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.

"Falling down": a retroperitoneal catastropheC.

Hemoperitoneum due to ruptured retroperitoneal varices is an extremely rare condition and a poor prognostic sign with a catastrophic and life-threatening situation. Early recognition affords appropriate management and urgent surgical intervention in order to favor the survival rate. In this case report we accurately describe the complex clinical course of a 56-year old woman with retroperitoneal varices, who few months earlier had a chest trauma with multiple left lower rib fractures and 10 years earlier she underwent to ovarian hyperstimulation for an ovulation induction. She was taken to the emergency room for a fainting episode with signs of a clear hemodinamic shock without a present history of trauma. The intricacy of this case was mostly due to the choice of the correct management, where the damage control resuscitation turned out to have an important role.

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.

[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.

The Ovarian Hyperstimulation Syndrome.

The ovarian hyperstimulation syndrome (OHSS) is an iatrogenic syndrome, which may, infrequently, become severe and evenly fatal. Until the last decade, the worldwide popularity of assisted reproductive technology (ART) and ovulation induction/controlled ovarian hyperstimulation employed in ART for either in vivo fertilization or in vitro fertilization, in the last two decades, has been accompanied by an increase in the cases of OHSS. In the last decade, the substitution of the human chorionic gonadotropin trigger with the gonadotropin-releasing hormone agonist trigger has decreased the incidence of this syndrome but did not eliminate it completely. We summarize here the classification, pathophysiology, and treatment of the OHSS.

Ovarian hyperstimulation syndrome management strategies: where are we going?

Ovarian hyperstimulation syndrome (OHSS) is one of the most frequent, serious and potentially lethal iatrogenic complications of controlled ovarian stimulation. Despite extensive research, the exact pathogenesis of this syndrome remains less clear, but there appears to be a relationship of increased vascular permeability mediated by HCG and other downstream mediators. Adequate experience with ovulation induction therapy and identifying patients with known risk factors are essential in preventing OHSS. As this is a completely iatrogenic disease numerous strategies have been investigated to help decrease the risk of OHSS and their effects on pregnancy and live birth rate. What follows is a review of the common strategies apply today to minimize risk of OHSS in patients undergoing assisted reproductive technologies.

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.

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.

Elective frozen-thawed embryo transfer (FET) in women at risk for ovarian hyperstimulation syndrome.

Elective cryopreservation of cultured embryos has become a treatment option for women at risk for ovarian hyperstimulation syndrome (OHSS). The aim of our study was to investigate the outcome of elective cryopreservation and consecutive frozen-thawed embryo transfer (FET) in a large IVF clinic in Austria. A total of 6104 controlled ovarian hyperstimulation cycles (COH) were performed on 2998 patients including 200 patients (6.7%) who were undergoing elective cryopreservation and FET due to high risk of OHSS. We estimated the cumulative live birth rate using the Kaplan-Meier method and evaluated independent predictors for successful live births with a Cox model. A total of 270 frozen-thawed embryo transfers were performed on 200 patients with up to 4 transfers per patient. The first embryo transfer showed a live birth rate of 42.0%, the second transfer showed a cumulative rate of 58.5%. After a total of 4 FETs from the same COH cycle, a cumulative live birth rate of 61.0% per COH cycle could be achieved. Four cases of OHSS occurred amongst these patients (2.0%), all of them of moderate severity. Multivariate analysis identified maternal age, the use of assisted hatching and the number of embryos transferred at the blastocyst stage as independent predictors for cumulative live birth. Our study clearly suggests that elective FET is safe and shows excellent cumulative live birth rates. This concept can, therefore, be used to avoid the severe adverse events caused by COH and the inefficient use of cultured embryos.

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.