An Idiopathic Case of Recurrent Spontaneous Ovarian Hyper Stimulation Syndrome

C l i n M e d International Library Citation: Ainsworth A, Khan Z, Jensen J (2016) An Idiopathic Case of Recurrent Spontaneous Ovarian Hyper Stimulation Syndrome. Obstet Gynecol Cases Rev 3:081 Received: December 20, 2015: Accepted: March 23, 2016: Published: March 26, 2016 Copyright: © 2016 Ainsworth A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Ainsworth et al. Obstet Gynecol cases Rev 2016, 3:081 Volume 3 | Issue 3


Introduction
Ovarian hyperstimulation syndrome (OHSS) is almost exclusively a complication of assisted reproductive technology (ART), with a reported incidence of 2.3% per patient [1].Increased risk of ART associated OHSS is found in patients of young age, low body weight, and polycystic ovary syndrome (PCOS) [2].Rarely, OHSS has been reported following spontaneous conception [3,4].Iatrogenic and spontaneous cases of OHSS are clinically alike.OHSS is characterized by significant ovarian enlargement, extravascular fluid shifts, and a spectrum of clinical outcomes ranging from mild nausea and vomiting to significant ascites, end organ hypoperfusion, and possible death.OHSS, regardless of etiology, will eventually resolve.However, resolution may take weeks and requires close surveillance and supportive therapy.We report a case of recurrent OHSS following spontaneous conception.

Case Report
A 29-year-old gravida 3, para 1-0-1-1, presented at 8 weeks gestation after spontaneous conception with progressive abdominal discomfort, nausea, and a three kilogram weight gain over the past week.She had established prenatal care at an outside institution prior to this visit.She had no personal history of thyroid disease, pituitary pathology, or polycystic ovary syndrome, and had never used medications for ovulation induction or undergone other fertility treatment.Her medical history was consistent with apparent spontaneous OHSS with her two prior pregnancies.There was no family history of spontaneous OHSS.
ISSN: 2377-9004 cabergoline was continued.The patient symptomatically improved on hospital day two.Repeat laboratory studies revealed decreasing hemoconcentration (Hgb 15.3 g/dL) and resolution of hyponatremia (132 mmol/L).A second thoracentesis removed 900cc of ambercolored fluid.She was discharged to home on hospital day two.
The patient was seen for follow-up the next day and complained of persistent dyspnea and progressive ovarian enlargement (19.7 × 14.7 × 12.9 cm and 18.2 × 13.2 × 13.1 cm) though pregnancy remained viable (Figure 1).She was followed closely as an outpatient, receiving five serial therapeutic thoracenteses.Her symptoms resolved thereafter, and the remainder of her pregnancy was uncomplicated.She was induced at 39 0/7 weeks and delivered a live born male via spontaneous vaginal delivery without complication.A postpartum tubal ligation was performed.

Discussion
Spontaneous OHSS results from excessive stimulation of follicle stimulating hormone (FSH) receptors on ovarian granulosa cells.This stimulation leads to the recruitment of additional granulosa cells, local estrogen production, and eventual recruitment of multiple dominant follicles.Upon luteinization, these follicles release vasoactive substances, most notably vascular endothelial growth factor (VEGF), leading to systemic capillary leakage, extravascular fluid shifts, and intravascular hypovolemia [2].Clinical outcomes range from mild patient discomfort to end-organ failure, coagulopathy risk and possible death.
The spectrum of OHSS has been classified based on signs, symptoms, and laboratory findings.Grade I OHSS is characterized by bilateral ovarian enlargement (≤ 5 × 5cm), serum estradiol greater than 1500 pg/mL, and progesterone concentration greater than 30 ng/mL.Grade II OHSS describes progressive ovarian enlargement (≤ 12 × 12 cm), abdominal discomfort, and gastrointestinal symptoms of nausea, vomiting, or diarrhea.Grade III OHSS is severe, and includes extreme ovarian enlargement (> 12 × 12 cm), ascites, pleural and/or pericardial effusion, electrolyte imbalances, hypovolemia, and hemoconcentration.
Patients with mild OHSS may be managed as an outpatient with daily communication of patient weight, abdominal circumference, and reported fluid intake and output.Serial laboratory evaluations for hematocrit, electrolytes, and creatinine should be reviewed for signs of disease progression.Hospitalization is required for serious disease.Indications for admission include uncontrolled pain, intractable nausea or vomiting, oliguria, dyspnea, electrolyte imbalances (hyponatremia: sodium < 135 mEq/L or hyperkalemia: potassium > 5 mEq/L), or hemoconcentration (Hct > 45%).Progression of symptoms, vital signs, and laboratory findings must be carefully monitored.
Supportive care with IV fluid hydration and ultrasound-guided paracentesis or thoracentesis may be needed to treat intravascular hypovolemia and extravascular volume overload.Anticoagulation with prophylactic Heparin or low molecular weight Heparin (LMWH) and intermittent pneumatic compression devices are strongly recommended to prevent thromboembolism.Dopamine agonists have been used to prevent and treat ovarian hyperstimulation syndrome by blocking expression of VEGF receptor [5].There have been no significant pregnancy complications attributed to use of dopamine agonists, such as cabergoline, in early pregnancy [6].Additionally, intensive care may be required for renal failure, pulmonary compromise, or life threatening thromboembolism [2].
Although few cases of spontaneous OHSS have been reported, multiple etiologies have been described.Both increased stimulation of normal ovarian FSH receptors and physiologic stimulation of mutated ovarian FSH receptors contribute to the pathologic recruitment of multiple dominant follicles.Increased circulating levels of FSH, caused by pituitary adenomas, have been identified as a primary cause of spontaneous OHSS [7][8][9][10].These cases required treatment by transsphenoidal tumor resection for resolution of symptoms.Conversely, normal levels of circulating FSH may lead to OHSS through activation of mutated FSH receptors.These mutations were first identified in 2003, by both Vasseur et al. and Smits et al. [11,12].Since then, new FSH mutations have been identified and additional cases of spontaneous OHSS described [13,14].There are reports of both live births and spontaneous miscarriage in cases of FSH receptor mutations.
Increased FSH receptor stimulation may also result from binding domain similarities in FSH, thyroid stimulating hormone (TSH), and human chorionic gonadotropin (HCG).Elevated levels of TSH, found in hypothyroidism have been described in two prior cases of spontaneous OHSS [15,16].The patients were started on levothyroxine and delivered at term.Similarly, elevated levels of HCG, as found in molar pregnancies or multiple gestations, have been found to stimulate normal ovarian FSH receptors and cause spontaneous OHSS [1,[17][18][19]].The reported cases ended in spontaneous miscarriage or pregnancy termination.Finally, polycystic ovary syndrome (PCOS)

Figure 1 :
Figure 1: Bilaterally enlarged ovaries with multiple large follicles and viable singleton intrauterine pregnancy.(A) Right ovary measuring 19.7 × 14.7 × 12.9 cm; (B) Left ovary measuring 18.2 × 13.2 × 13.1 cm; (C) Intrauterine pregnancy with cardiac pulsations.Ovarian size can be appreciated in contrast with the size of the gravid uterus.