Author
Information
Chhatrapati A*, Nadkarni T**, Mishra I*, Jassawalla MJ.***.
(*Assistant
Professor, ** Additional Professor, ***Honorary Professor and unit head Department
of Obstetrics and Gynecology, Nowrosjee Wadia Maternity
Hospital , Mumbai , India
Abstract
Most of the ovarian hyperstimulation (OHSS) cases
occur due to ovulation induction followed by HCG trigger. But OHSS may rarely
occur in cases of multifetal gestation, hypothyroidism or polycystic ovarian
syndrome. We report a case of OHSS in a spontaneous pregnancy in a primigravida
with twin pregnancy with severe hypothyroidism. The clinical presentation
included severe abdominal discomfort. After ultrasound examination the
diagnosis was confirmed. Patient was managed conservatively.
Introduction
Ovulation induction therapy sometimes leads to ovarian
hyperstimulation syndrome which occurs in the luteal phase especially after HCG
trigger for ovulation. The syndrome was first described in 1941. In very rare
spontaneous pregnancies OHSS can occur due to follicle stimulating hormone
receptor gene mutations. The likelihood is more if it is associated with
maternal hypothyroidism or multifetal pregnancy. The symptoms vary; nausea,
vomiting and abdominal discomfort in mild OHSS and ascites, hydrothorax,
thromboembolism and renal failure in severe form. Treatment is mainly
supportive.
Case Report
A 21 year old primigravida married since 1 year 6
months was referred to our hospital with 2 and a half months amenorrhea and severe
abdominal discomfort. Urine pregnancy test was done which was positive. Patient
was stable clinically. Ultrasound (USG) was done. Her USG detected, a monochorionic
monoamniotic twin pregnancy with multiple ovarian cysts bilaterally and mild
free fluid in the pelvis. Right ovary measured 9.4x7.2 cm with multiple cysts,
largest being 3x3 cm. Left ovary measured 11x8 cm with multiple cysts, largest
measuring 5x5 cm. Patient did not give history of receiving any ovulation
induction agents. Patient was admitted for evaluation and further management.
On physical examination, patients’ vital parameters
were stable. Abdomen was soft non tender. On per vaginal examination uterine
size was 12 weeks. Bilateral ovaries were cystic. Laboratory investigations
revealed severe anemia ( Hb 6.4 gm% ), hematocrit ( 20.1% ), normal blood
electrolytes, blood urea nitrogen ( 10 mg/ dL ), creatinine ( 0.8 mg/ dL ) and
coagulation profile ( PT/INR 1.0 ). SGOT/SGPT was slightly raised ( 43/35
units/l ). Serum proteins were normal ( Total 6.9 g/ dL; A/G 4.2/2.7 g/ dL).
Serum β HCG was above 300,000 mIU/ ml
which was corresponding to the weeks of gestation. Serum TSH was very high
(> 100 uIU/ ml) suggestive of severe hypothyroidism. Serum estradiol (E2)
was 4720 pg/ ml and serum progesterone was 353.41 ng/ ml which was high. Patient
was managed conservatively. Hemoglobin electrophoresis was normal. Correction
was done with 2 units of packed red cell transfusion. Post transfusion Hb was 9.3
gm% and PCV was 31.7%. For hypothyroidism 100 ug of levo thyroxine was started after
consultation with the endocrinologist. At 11 weeks nuchal translucency/ nasal
bone (NT/ NB) scan was performed which was normal. There was no change in the
size of the ovarian cysts. As patient was symptomatically better she was
discharged after 15 days observational period. She followed up in OPD
regularly; but she aborted spontaneously; complete abortion at 17 weeks of
gestation. USG pelvis done after 10 months of abortion was completely normal.
Patient was advised to try for natural conception with early ANC registration.
Figure 1. Hyperstimulated Right Ovary
Figure 2. Hyperstimulated Left Ovary
Figure 3. Monoamniotic Twin
Discussion
Ovarian hyperstimulation syndrome very rarely occurs
in a spontaneous pregnancy. Iatrogenic OHSS occurs following HCG trigger for
ovulation, hence is seen at about 3-5 weeks of amenorrhea. But spontaneous
occurs between 8-14 weeks. Recently the Follicle Stimulating Hormone (FSH) receptor
gene mutations are identified which leads to increased sensitivity to
circulating HCG in spontaneous OHSS.[1]
De Leener has proposed a classification of spontaneous OHSS syndrome
into three types according to clinical presentation and FSH receptor mutation.
Type I : Due to mutation in FSH receptor gene. The
recurrence rate of spontaneous OHSS is very high in this type.
Type II : Due to high circulating HCG which is seen in
multifetal pregnancies or in molar pregnancies, this is most common type.
Type III : Associated with maternal hypothyroidism.[2]
In pregnancies where ovulation induction is done by
FSH, the follicular recruitment and enlargement is found during exogenous FSH
administration and can lead to iatrogenic OHSS. In spontaneous pregnancies, the
follicular recruitment and growth occur later due to abnormal stimulation of
the mutated FSH receptor that is abnormally sensitive to normal levels of
circulating HCG, produced by syncytiotrophoblast of pregnancy. Hence the
spontaneous cases of OHSS generally develops at 8 weeks amenorrhea and resolves
spontaneously at the end of the first trimester of pregnancy.[3]
In literature many cases were described as spontaneous
pregnancy with OHSS and maternal hypothyroidism. In these cases it is assumed
that high levels of thyroid stimulating hormone stimulate ovaries directly due
to structural resemblance to FSH and can cause ovarian hyperstimulation.[4,5]
In our case hypothyroidism was present. The pathophysiology of spontaneous OHSS
associated with hypothyroidism is not well understood. The various theories are
(a) in hypothyroid patients, there are high levels of circulating estriol
produced through 16 hydroxylation (less
potent estriol) as against 2 hydroxylation pathways (more potent estriol) seen
in normal patients. This causes decreased negative feedback regulation and
excessive release of gonadotropins by ovary.
(b) High levels of thyroid stimulating hormone can directly stimulate
ovaries in women with hypothyroidism and can cause ovarian hyperstimulation.[6]
OHSS can be classified according to the degree of
severity of affection as mild, moderate severe and critical. Royal College
The management of OHSS depends on the degree of
severity. Early recognition and prompt appropriate treatment will avoid serious
consequences. Medical treatment, undertaken in first line, may be insufficient.
Therapy is supportive, syndrome being self-limiting. Mild cases can be managed
on OPD basis with daily measurement of weight and monitoring urinary output.
Serial measurement of hematocrit, electrolyte and creatinine are done. Severe
OHSS requires hospital admission and prompt management to replace lost
intravascular volume and prevent its potentially fatal complications namely
renal failure and thromboembolic events.[9] Sometimes drainage of fluid or
debulking of ovarian cysts may be needed.[10]
Conclusion
OHSS is very rare but potentially serious
complication. The exact etiology is not known conclusively but further research
is going on. Certain factors like high levels of HCG hormone found in early
pregnancy in cases of multifetal gestation and molar pregnancy and mutations in
the follicle stimulating hormone (FSH) receptor gene, which leads to an
increased sensitivity to HCG, may be some of the possible etiologies. Twin pregnancies
and hypothyroid patients are more prone to OHSS. If we diagnose and manage
spontaneous OHSS at the appropriate time we can prevent any severe
complication.
Acknowledgment
Dr. Umesh Athawale, Athawale Diagnostic center for the
ultrasound examinations.
References
- Delbaere A, Smits G, Olatunbosun O, Pierson R, Vassart G, Costagliola S. New insights into the pathophysiology of ovarian hyperstimulation syndrome- What makes the difference between spontaneous and iatrogenic syndrome? Hum Reprod. 2004 Mar;19(3):486–9.
- De Leener A, Montanelli L, Van Durme J, Chae H, Smits G, Vassart G, et al. Presence and absence of follicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology. J Clin Endocrinol Metab. 2006;91(2):555–62.
- Ozer Oztekin, Ferit Soylu, Orkan Tatli. Spontaneous
ovarian hyperstimulation syndrome in a normal singleton pregnancy.
- Ayhan A, Tincer ZS, Aksu AT. Ovarian hyperstimulation syndrome associated with spontaneous pregnancy. Human Reproduction. 1996;11(8):1600–1601.
- Rothmensch S. Spontaneous ovarian hyperstimulation syndrome associated with hypothyroidism. Am J Obstet Gynecol. 1989;160:1220–1222.
- Taher BM, Ghariabeh RA, Jarrah NS, Hadidy AM, Radaideh AM, Ajlouni KM. Spontaneous ovarian hyperstimulation syndrome caused by hypothyroidism in an adult. Eur J Obstet Gynecol Reprod Biol. 2004;112:107–9.
- Jenkins JM, Drakeley AJ, Mathur RS. The Management of Ovarian Hyperstimulation Syndrome. Green-top Guideline. 2006 Sep;(5):1–11.
- Vloeberghs V, Peeraer K, Pexsters A, D'Hooghe T. Ovarian hyperstimulation syndrome and complications of ART. Best Pract Res Clin Obstet Gynaecol. 2009 Oct;23(5):691–709. [PubMed]
- Davis M, Kennedy R. Ovarian hyperstimulation syndrome: Aetiology, prevention and management. Reviews in Gynaecological and Perinatal Practice. 2006;6:26–32.
- Aboulghar MA, Mansour RT, Serour GI, Amin Y. Ultrasonically guided vaginal aspiration of ascites in the treatment of severe ovarian hyperstimulation syndrome. Fertil Steril. 1990 May;53(5):933–5.
Chhatrapati A, Nadkarni
T, Mishra I, Jassawalla MJ. Ovarian
Hyperstimulation Syndrome In a Spontaneous Twin Pregnancy With Hypothyroidism. JPGO
2016. Volume 3 No. 3. Available from: