Inferring biallelism of two FSH receptor mutations associated with spontaneous ovarian hyperstimulation syndrome by evaluating FSH, LH and HCG cross-activity.

RESEARCH QUESTION: What is the cumulative effect of two follicle-stimulating hormone receptor (FSHR) mutations in spontaneous ovarian hyperstimulation syndrome (sOHSS) pathogenesis? Are these mutations in the mono- or biallelic state? DESIGN: Two FSHR mutations were found in a pregnant patient affected by sOHSS with no predisposing conditions. While the p.Asn106His mutation is novel, the p.Ser128Tyr mutation has been associated with sOHSS previously. The patient's FSHR gene was analysed by Sanger sequencing, and FSHR cDNAs carrying a single or both point mutations were created by mutagenesis in vitro. cAMP activation by recombinant FSH, luteinizing hormone (LH), human chorionic gonadotropin (HCG) and thyroid-stimulating hormone (TSH) was evaluated in transfected HEK293 cells by bioluminescence resonance energy transfer. RESULTS: All mutations decreased the 50% effective concentration of FSH calculated for cAMP (P < 0.05, n = 6), resulting in two- to 10-fold lower ligand potency. TSH failed to induce an FSHR-mediated increase in intracellular cAMP, while LH was approximately four-fold more potent than HCG in p.Ser128Tyr FSHR-expressing HEK293 cells despite lower cAMP plateau levels (P < 0.05, n = 5). The p.Ser128Tyr FSHR mutation was found to be responsible for an LH-/HCG-induced increase in cAMP when it was in the biallelic heterozygous state with p.Asn106His, but no increase in cAMP was induced in the monoallelic state. CONCLUSION: In-vitro data support that, in pregnant patients with sOHSS, the two FSHR mutations have an opposing effect on the pathogenesis of sOHSS and are in the biallelic heterozygous form, allowing HCG to induce a p.Ser128Tyr FSHR-mediated increase in cAMP.

Lifesaving dose increment of cabergoline in life-threatening spontaneous ovarian hyperstimulation syndrome resistant to all interventions.

OBJECTIVE: Spontaneous ovarian hyperstimulation syndrome (SOHSS) is an extremely rare complication that deserves a multidisciplinary approach together with a thorough investigation for the correct diagnosis of the underlying pathology. The aim of this study was to present a case of severe SOHSS resistant to all interventions and to discuss the available interventions to overcome such a rare and serious clinical situation. CASE REPORT: We report a case of severe, life-threatening spontaneous OHSS with a normal nine weeks singleton pregnancy in a 25-year-old nulliparous woman, which resulted with pregnancy termination and continuation of disease progression until the dose of cabergoline was increased to 1.5 mg/day. CONCLUSION: This case report emphasizes that patients with life-threatening SOHSS resistant to all medical and surgical interventions may benefit from higher doses of cabergoline. Although spontaneous OHSS is extremely rare, it is potentially a life-threatening clinical entity in its severe form and needs time management and detailed examination of the underlying causes.

First mutation in the FSHR cytoplasmic tail identified in a non-pregnant woman with spontaneous ovarian hyperstimulation syndrome.

BACKGROUND: Spontaneous ovarian hyperstimulation syndrome (sOHSS) is a rare event occurring mostly during natural pregnancy. Among described etiologies, some activating mutations of FSH receptor (FSHR) have been identified. CASE PRESENTATION: We report hereby the case of a non-pregnant women with three episodes of sOHSS. Hormonal evaluation was normal and no pituitary adenoma was detected. However, genetic analysis identified a novel heterozygous FSHR mutation (c.1901 G > A). This R634H mutation is the first described in the cytoplasmic tail of the receptor. Functional analysis failed to reveal constitutive activity of the mutant but a decreased cAMP production in response to FSH. The weak activity of this mutant is correlated with a markedly reduced cell surface expression. CONCLUSION: Pathophysiology of non gestationnal sOHSS is still ill established. The molecular characterization of this new mutant indicates that it might not be at play. Therefore, further investigations are needed to improve knowledge of the molecular mechanism of this syndrome.

A case of ovarian torsion in a patient carrier of a FSH receptor gene mutation previously affected by spontaneous ovarian hyperstimulation syndrome.

We here report a case of ovarian torsion in a patient with an history of two previous episodes of spontaneous ovarian hyperstimulation syndrome during her two pregnancies. A mutation of follicle-stimulating hormone receptor (FSHr) gene was identified in this patient and in other members of the family. Two years after her successful second pregnancy, the patient showed signs of severe thyroiditis during administration of oral contraceptive, with suppressed TSH and increased thyreoglobulin, in the absence of any abnormalities of the auto-antibodies. In few days, she developed severe pelvic pain and ultrasonographic evidence of increased ovarian volume. She underwent laparoscopy with unilateral adnexectomy for ovarian ischemic necrosis due to adnexal torsion. Our experience suggests that patients' carrier of a mutation of FSHr gene are at risk of ovarian pathologies also when non-pregnant and in the presence of low TSH levels. Further investigations are needed for an appropriate knowledge of typical and atypical manifestations of spontaneous ovarian hyperstimulation syndrome.

Spontaneous Ovarian Hyperstimulation Syndrome Associated With Primary Hypothyroidism.

Ovarian hyperstimulation syndrome is a rare condition in pregnant women. Most cases are associated with the use of ovulation induction and stimulation medications. Some studies have reported cases of this condition in non-pregnant women or women undergoing ovulation therapy. In this case report, we report the case of a 27-year-old pregnant Saudi woman presenting with a picture of severe spontaneous ovarian hyperstimulation syndrome secondary to severe undiagnosed hypothyroidism. Treatment with Eltroxin (thyroxine) led to complete improvement and regression of ovarian enlargement after empirical titrating thyroxin replacement therapy, which proved the presence of this causation. The diagnosis was confirmed by laboratory and imaging findings, which helped prompt management and prevented complications of unneeded surgical intervention.

A case report of spontaneous ovarian hyperstimulation syndrome and the long-term management of the endocrine disorder.

Background: Spontaneous ovarian hyperstimulation syndrome (sOHSS) is a rarely reported clinical symptom of uncertain origin with the incidence of 0.2-1.2%. There is no report of the patients' follow-up situation after the remission of the clinical symptom and this is the first one. The aim of this study was to remind the medical staff of the necessity of long-term management. Case Description: We report a case of severe sOHSS with a normal 15 week gestation twin pregnancy in a 21-year-old primigravida who presented in our emergency room result from the 1 week's nausea and vomiting and progressively aggravated abdominal distension and pains for 3 days. The patient in our case had no significant precipitating factors and she had no previous outstanding medical history except that she had experienced acute glomerulonephritis when she was 9 years old. On ultrasound imaging, we found abnormally enlarged ovaries and massive ascites and moderate pleural fluid. A diagnosis of spontaneous ovarian hyperstimulation was made. The patient participated in followed-up visits for 1 year and experienced polycystic ovary syndrome (PCOS) and weight loss which up to 15kg after delivery. Conclusions: Typically, although sOHSS is potentially life-threatening, its clinical detection is often delayed. A proactive strategy should be encouraged in the management of high-risk patients. The therapeutic schedule of mild-to-moderate sOHSS can focus on symptomatic relief and supportive treatment. Our case report elucidates the possible long-term effects of sOHSS and reminds us of the need for long-term management of those affected.

Follicle-Stimulating Hormone-Secreting Pituitary Adenoma Inducing Spontaneous Ovarian Hyperstimulation Syndrome, Treatment Using In Vitro Fertilization and Embryo Transfer: A Case Report.

Objective: To describe the management of a patient with a pituitary adenoma secreting follicle-stimulating hormone (FSH) associated with spontaneous ovarian hyperstimulation syndrome (sOHSS) who was treated with in vitro fertilization and embryo transfer (IVF-ET). Methods: We report a clinical case of a woman of reproductive age with menstrual irregularity, infertility and ovarian hyperstimulation due to recurrent pituitary adenoma secreting FSH, which persisted after transsphenoidal surgery.She underwent the diagnosis by magnetic resonance imaging (MRI) and laboratory tests,and finally she was treated with IVF-ET. Results: The patient was plagued by a recurrent pituitary adenoma for many years and tried various treatments. After complete transsphenoidal surgery, sOHSS decreased, as shown by a reduction in oestradiol levels and an improvement in the ultrasonography parameters; however, secondary amenorrhea occurred. Finally, pregnancy was achieved through IVF-ET and the symptoms of ovarian hyperstimulation were relieved. Conclusions: IVF-ET was found to be effective for the treatment of recurrent pituitary adenoma, thus representing a therapeutic option that should be taken into consideration in such cases.

Spontaneous Ovarian Hyperstimulation Syndrome: A Report of Two Cases from Different Pathogenesis.

Spontaneous ovarian hyperstimulation syndrome (s-OHSS) is a rare finding that occurs in early pregnancy. There is a rapidly increasing ovarian size secreting vasoactive substances that lead to fluid shift into third spaces. This occurs in the absence of exogenous hormonal therapy. We present two cases of s-OHSS. A 35-year-old gravida 4 para 3 presented with complaints of progressive abdominal pain, distension, nausea, vomiting, and difficulty in breathing at 10 weeks gestation. On imaging, a singleton intrauterine gestation, enlarged ovaries containing multiple cysts, and moderate ascites were seen. Second, a 17-year-old primigravida presented with abdominal distension and pain and bleeding per vaginam following 4 months amenorrhea. A bulky uterus containing a large hyperechoic structure with multiple cystic spaces in keeping complete molar gestation and enlarged ovaries containing multiple cysts were seen on ultrasound imaging. The singleton gestation was managed successfully to term with conservative therapy tailored to clinical symptoms.

Spontaneous ovarian hyperstimulation syndrome in a nonpregnant female patient: a case report and literature review.

Spontaneous ovarian hyperstimulation syndrome (sOHSS) usually occurs in patients with a spontaneous ovulation cycle, especially in those with multiple pregnancies combined with hypothyroidism and polycystic ovary syndrome. sOHSS rarely occurs in women who are not pregnant. A 23-year-old woman with obvious abdominal distension visited our hospital. The patient was not pregnant and had not undergone controlled superovulation. Apart from abdominal distension, the patient denied any symptom of obvious incentives, abdominal pain, abnormal vaginal bleeding, or drainage. Biochemical analysis showed a high carbohydrate antigen-125 level and low total protein and albumin levels. Abdominal ultrasound and computed tomography showed a large amount of ascites and cystic uneven masses with an irregular shape in the area of the ovaries and fallopian tubes. Post-surgical histopathology indicated the diagnosis of sOHSS. Wedge resection of both ovaries was performed. Symptomatic treatment was further performed and the patient recovered well. Our findings indicate that sOHSS can occur in women who are not pregnant. Additionally, besides the follicle-stimulating hormone receptor gene mutation hypothesis, the pathogenesis of sOHSS should be further studied.

Ovarian torsion and spontaneous ovarian hyperstimulation syndrome in a twin pregnancy: A case report.

INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is extremely rare in spontaneous pregnancies. Spontaneous OHSS can result from glycoprotein hormones stimulating follicle-stimulating hormone receptors (FSHR). PRESENTATION OF CASE: We report a twin pregnancy in which ovarian torsion and hemoperitoneum complicating OHSS were treated with left adnexectomy and aspiration. The only trigger for spontaneous OHSS in this case was high levels of chorionic gonadotropin hormone. DISCUSSION: Multiple pregnancy, gestational trophoblastic disease, primary hypothyroidism, thyroid-stimulating hormone/gonadotropin-secreting adenomas, and mutations of the FSHR gene may trigger spontaneous OHSS. CONCLUSION: Spontaneous OHSS should be included in the differential diagnosis of acute abdomen in pregnant women; if spontaneous OHSS is diagnosed, the etiology should be determined in order to focus the treatment and avoid future complications.

Novel FSH receptor mutation in a case of spontaneous ovarian hyperstimulation syndrome with successful pregnancy outcome.

The objective is to study the FSH receptor (FSHR) for mutations in a case of spontaneous ovarian hyperstimulation syndrome (sOHSS). This is a single case study and it examined patient who presented with spontaneous critical OHSS in early pregnancy and had successful good obstetric outcome. Intervention of this study was analysis of blood for genetic analysis of FSHR postdelivery. The main outcome measure noted was FSHR mutation. The study resulted in a novel, here though unreported, heterozygous mutation in FSHR gene at nucleotide position 1346 (AC(1346)T to AAT) in exon 10 yielding a threonine to asparagine (Thr(449)Asn) substitution in the transmembrane domain helix 3 of the FSHR. To conclude FSHR gene analysis can add to our understanding of sOHSS.

Laparoscopic detorsion for bilateral ovarian torsion in a singleton pregnancy with spontaneous ovarian hyperstimulation syndrome.

A 26-year-old primigravida with a singleton pregnancy of 9 weeks gestation presented with severe lower abdominal pain, following spontaneous hyperstimulation of the ovaries in a natural conception. Emergency laparoscopy was done and bilateral ovarian torsion with retained vascularity was noted. Bilateral detorsion with ovarian puncture and ovariopexy was performed. A review of international literature suggests that this is the first case reported with bilateral ovarian torsion following spontaneous ovarian hyperstimulation syndrome in a singleton pregnancy.

Spontaneous ovarian hyperstimulation syndrome: case report, pathophysiological classification and diagnostic algorithm.

Spontaneous ovarian hyperstimulation syndrome is an extremely rare condition that occurs in the absence of ovarian hyperstimulation treatment. It can lead to significant morbidity and mortality, and therefore early diagnosis and supportive treatment are essential. We report an affected mother and her daughter with a previously reported heterozygous activating mutation in the FSHR gene. We performed a literature review with particular regard to pathogenesis, with a view to suggesting a pathophysiological classification system and a diagnostic algorithm to assist in the management of this rare condition.

Spontaneous ovarian hyperstimulation syndrome in a young female subject with a lingual thyroid and primary hypothyroidism

No abstract available.

Spontaneous ovarian hyperstimulation syndrome in a young female subject with a lingual thyroid and primary hypothyroidism

No abstract available.