Recurrent Ovarian Hyperstimulation Syndrome Research Articles

Recurrent spontaneous ovarian hyperstimulation secondary to hypothyroidism in an adolescent girl

Ovarian hyperstimulation syndrome (OHSS) is characterized by ovarian enlargement due to multiple ovarian cysts and a fluid shift into the extravascular space [1]. Some forms of OHSS have reportedly occurred during spontaneous pregnancy such as multiple pregnancies and associated conditions including, hypothyroidism, polycystic ovary syndrome, and follicle-stimulating hormone receptor (FSHr) mutations [2–4]. This report describes a case of recurrent OHSS associated with hypothyroidism in an adolescent girl with a non-remarkable family history and normal FSHr. An 18-year-old adolescent girl was admitted to our hospital with symptoms of abdominal pain and distension. Transabdominal ultrasonography (USG) showed mild ascites and bilateral ovarian multilocular cysts extending into the midabdomen. The results of blood counts and electrolyte analyses were normal. The hormonal evaluation revealed undetectable human chorionic gonadotropin (hCG), normal follicle-stimulating hormone (FSH) (6.5 IU/L) and luteinizing hormone (LH) (9.2 IU/L), high estradiol (E2) (4.000 mIU/mL) and thyroid-stimulating hormone (TSH) (100 lU/mL; normal range 0.47–5 lU/mL), and low free thyroxine (4.5 pmol/L; normal range 11–24 pmol/L). Abdominal magnetic resonance imaging (MRI) showed massively enlarged bilateral multicystic structures of presumable bilateral ovarian origin extending into the midabdomen (Fig. 1). Pituitary MRI was normal. Conservative medical management comprising was considered due to the presence of moderate spontaneous OHSS. Oral thyroxine (levothyroxine at 100 lg/day) was instituted on the basis of hypothyroidism. Abdominal symptoms were relieved with the beginning of menstruation within 2 weeks. Four months later, the patient presented to our center with similar symptoms. USG findings were similar to bilateral multilocular cysts in both ovaries and mild ascites. Serum hormonal analysis revealed a higher E2 level (10.000 mIU/mL) with a high TSH (20 lU/mL) and normal free thyroxine (15 pmol/L). Blood counts and electrolyte analyses were normal. Observation and supportive medical treatment was considered. The patient was discharged after 10 days with complete resolution of all clinical symptoms. Oral thyroxine reached a dose of 200 lg/day. Hormonal tests for thyroid function were normal 2 months after her second admission and the ovarian cysts completely regressed after 6 months. Bidirectional DNA sequencing of the FSHr gene was performed by PCR amplification to rule out FSHr abnormality in this case. No differences in the DNA sequence in the 10 exons were observed between the wild-type FSHr gene and those obtained from the patient. The exact mechanism underlying the relationship between OHSS and hypothyroidism is not clearly understood. One explanation of this rare association is that TSH has weak FSH activity on mutated FSHr, causing ovarian stimulation [5]. Another explanation is based on the release of FSH and LH by low levels of thyroid hormones, in addition to the targeted activation of TSH release. This seemed to be the cause in our case as FSHr sequencing was normal. In the literature, all the reported recurrent form of O. Erol (&) H. Ayik A. U. Derbent Department of Obstetrics and Gynecology, Antalya Research and Education Hospital, 07050 Antalya, Turkey e-mail: dronurerol@hotmail.com

Recurrent spontaneous ovarıan hyperstımulatıon ın a virgın girl

Ovarian hyperstimulation syndrome (OHSS) develops due to the release of vasoactive mediators induced by excessively luteinized and enlarged ovaries. Most OHSS cases are iatrogenic subsequent to ovulation induction. We report the first case of recurrent OHSS developed during normal menstral cycle in a virgin girl, diagnosed with ultrasonography and magnetic resonance imaging.

Case report: a most peculiar family with spontaneous, recurrent ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) mostly occurs as a complication of induction of ovulation. However, rarely, it may occur spontaneously at the beginning of a natural pregnancy and in the absence of any assisted reproductive treatment. Spontaneous OHSS has been reported in pregnant women affected by hypothyroidism, polycystic ovary syndrome, gonadotropin-producing pituitary adenoma, but also in normal pregnancies. The aetiology of this condition is still unclear. We hereby report on a case of spontaneous, familial, recurrent OHSS in a 26-year-old primipara whose first-degree cousin, paternal grandmother and a number of other members of her father’s family had suffered from a similar condition. This case seems to support the concept of a genetic predisposition for spontaneous OHSS thereby suggesting the need for preventive and therapeutic strategies.

A Mutation in the Follicle-Stimulating Hormone Receptor as a Cause of Familial Spontaneous Ovarian Hyperstimulation Syndrome

Ovarian hyperstimulation syndrome (OHSS) occurs mainly after excessive stimulation of the ovaries by exogenous gonadotropins administrated in the context of in vitro fertilization procedures (iatrogenic OHSS). Recently, spontaneous and recurrent occurrence of the disease (spontaneous OHSS) was shown in two families to be caused by mutations affecting the follitropin receptor (FSHr). The two mutant FSHr (T449I, D567N) harbor aminoacid substitutions in the serpentine portion of the receptor and display abnormally high sensitivity to the pregnancy hormone hCG, thus providing a satisfactory explanation to the phenotype. In addition, mutant D567N showed also increased sensitivity to thyrotopin (TSH) and displayed increase in basal (ligand-independent) activity. In this report, we describe a new familial case of recurrent OHSS. The affected women were heterozygous for a different mutation involving codon 449, where an alanine was substituted for threonine. Similar to D567N, the T449A FSHr mutant shows an increase of its sensitivity to both hCG and TSH, together with an increase in basal activity. Together with the two previous studies, this report shows that inappropriate stimulation of the FSHr by hCG is a cause of spontaneous OHSS.