spontaneous ovarian hyperstimulation syndrome ( sohss ) is now a recognized entity , defined as ohss appearing in patients with no history of stimulatory infertility treatment .
ohss , which otherwise may occur in normal pregnancies ( type i ohss ) , is now reported to be associated with mutated fsh receptor ( fshr ) gene , which may lead to recurrent sohss in patients presenting the mutations .
type ii is secondary to high levels of human chorionic gonadotropin ( hcg ) , while type iii coexists with hypothyroidism .
a 29-year - old female married since 1 year , primigravida with 3 months amenorrhea and ultrasonographic gestational age of 8 weeks and 5 days , presented with acute onset of abdominal distension , vulval edema and breathlessness .
there was no vomiting , trauma , fever , bleeding , or spotting per vaginum .
she had regular past menstrual cycles and no symptoms suggestive of renal , cardiac , or liver disorders .
ultrasonography done a few weeks prior to presentation revealed a normal intrauterine pregnancy and adnexae [ figure 1 ] .
ultrasonography images showing normal endometrial cavity ( intrauterine pregnancy ) and bilateral ovaries the patient was conscious , cooperative , afebrile , with no tachycardia and normotensive .
abdominal examination revealed shiny skin , tense ascites with no guarding , rigidity , or tenderness .
history was reconfirmed ; patient had not sought any medical advice or treatment for fertility enhancement .
blood investigations revealed hyponatremia ( 125 meq / l ) and hypoalbuminemia ( 3.4 gm / dl ) .
hemoglobin , white blood cell count , platelet count , coagulation profile , liver enzymes , blood urea nitrogen , and serum creatinine were normal .
estradiol was elevated at 12927 pg / dl ( normal range 188 - 2497 pg / dl ) .
ultrasonography revealed a multiloculated cystic lesion of size 17 cm  11 cm with vascularity within the wall of cystic lesion .
features of ohss were confirmed on magnetic resonance imaging ( mri ) [ figure 3 ] .
ultrasonography b - mode images show intrauterine fetus with multiple cysts involving both the right and left ovary .
there is mild free fluid in the intra - peritoneal cavity with left pleural effusion t2-weighted magnetic resonance imaging pelvic coronal images show t2-hypo intense lesion in the intrauterine cavity suggestive of fetus .
there are hyper intense multiple cysts seen without any mural nodule arising from both right ( in right iliac fossa ) and left ovary ( in pouch of douglas ) vital parameters , intake - output , and abdominal girth were monitored .
additional intravenous fluids were omitted , oral fluids were encouraged , and diuretics were initially required .
intravenous albumin infusion was instituted ( 25 g in 0.1 l solution per day for 7 days ) .
no interventional procedure was done for ascites and pleural effusion , both of which reduced , along with the adnexal mass .
unfractionated heparin 5000 u subcutaneous injection twice daily was instituted and continued for 9 days .
regular ultrasonographic monitoring showed further reduction in size of adnexal mass . at 40 weeks gestation ,
patient underwent cesarean section in view of nonprogress of labor and delivered a healthy male of 2.85 kg .
intraoperatively , an left ovarian simple cyst of 5 cm  5 cm was observed , for which no intervention was done .
postoperative mri revealed simple left ovarian cyst of 2 cm  2 cm , right side normal and involuting uterus [ figure 4 ] . t2-weighted magnetic resonance imaging pelvis images
6 weeks postpartum show complete resolution of bilateral cystic lesions with a single follicular cyst in the left ovary and multiple small follicles in the right ovary to investigate further , if ovarian hyperstimulation observed in this patient was due to any mutation in fshr gene , the patient was called back after delivery . the entire exonic region of fshr gene was screened for known / novel mutations as described earlier . to our interest
, we identified a novel heterozygous mutation in fshr gene leading to a change at amino acid position 449 [ figure 5 ] .
this was observed to be a transversion at nucleotide position 1346 ( act to aat ) in exon 10 yielding a threonine to asparagine ( thrasn ) substitution in the transmembrane domain helix 3 of the fshr .
( a ) electropherogram of 5-3 strand of the exon 10 of fshr gene , showing a wild type sequences ( upper panel ) of a control subject and heterozygous mutant sequence ( lower panel ) resulting in change of nucleotide  c to  a / c ( 1346 position ) leading to thrasn substitution identified in patient who developed spontaneous ovarian hyperstimulation syndrome during pregnancy .
the majority of ohss cases are usually iatrogenic and are induced by exogenous hormonal therapy .
the pathophysiology is one of the fluid extravasations , and the mediator appears to vascular endothelial growth factor . with respect to the severity of clinical picture
, it can be classified into : 
 grade 1 : abdominal distension and discomfortgrade 2 : grade 1 + nausea , vomiting , and/or diarrhea , ovaries 512 cmgrade 3 : grade 2 and ultrasonic evidence of ascitesgrade 4 : grade 3 and/or hydrothorax or dyspneagrade 5 : all above with hemoconcentration , coagulation abnormalities , and diminished renal perfusion ( critical ohss ) . 
 
grade 1 : abdominal distension and discomfort grade 2 : grade 1 + nausea , vomiting , and/or diarrhea , ovaries 512 cm grade 3 : grade 2 and ultrasonic evidence of ascites grade 4 : grade 3 and/or hydrothorax or dyspnea grade 5 : all above with hemoconcentration , coagulation abnormalities , and diminished renal perfusion ( critical ohss ) .
however , it is now being recognized and slowly coming to light , in the form of individual case reports that a similar clinical picture can occur in patients , unrelated to exogenous hormone administration . after a sufficient number of cases of sohss
were reported based on the underlying primary abnormality and the triggers leading to the sohss , de leener et al . ,
have proposed a 4-group classification for this abnormality , which is shown in table 1 .
classification of fsh receptor mutation our patient was classified as type 1 critical sohss in pregnancy and managed as per existing guidelines .
though the reports of successful completion of pregnancies complicated by sohss have been few , the conservative management recommended by the existing guidelines is validated by these few successful outcomes .
the understanding of the molecular basis of sohss is very recent , evident by the fact that the first recognition of a mutation in the fshr gene resulting in ohss was described very recently .
interestingly , all the activating mutations of fshr gene reported in women till date are associated with sohss leading to the activation of the receptor .
these mutations have been reported to cause loss of ligand binding specificity and increased response to hcg ( especially in first trimester when the levels of hcg are high ) resulting in hyperstimulation .
this mutation leads to the substitution of threonine to asparagine at amino acid position 449 in fshr .
however , the functional analysis of this mutation needs to be investigated to understand the pathophysiology at the molecular level . in the wake of this finding
at this point in time , much is yet to be understood about sohss and the molecular mechanisms behind it , and hence the reason of presenting this case report : a novel mutation in a condition , not fully understood .
the general gynecologist / obstetrician should have a high index of suspicion for sohss , as this entity can have several implications .
genetic analysis should be considered in all patients with sohss to improve our understanding of this entity , paving way for an earlier recognition and improved management of this condition .
 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 ( ac1346 t to aat ) in exon 10 yielding a threonine to asparagine ( thr449asn ) substitution in the transmembrane domain helix 3 of the fshr . to conclude fshr gene analysis can add to our understanding of sohss . 