Our data over a 6-year period indicate that there is no relationship between OIT and subsequent malignant ovarian tumour development among patients at our centre. Although the cytologic results of the ascitic cells from patients with severe OHSS were initially suggestive of malignancy, these patients did not develop any evidence of malignant ovarian tumours.
Because the risk of malignant ovarian tumours in is higher in nulliparous women, greater vigilance is necessary when treating this group. Bimanual examination and vaginal ultrasonography are essential. The best method to examine for enlarged ovaries is colour-Doppler ultrasound. Rarely, laparoscopy or laparotomy may be necessary. Therapy should only begin after malignant ovarian tumours have been ruled out and/or benign tumours have been removed.
Tumour markers, although useful, cannot differentiate ovarian enlargement caused by overstimulation from enlargement due to a malignancy. For example, the serum CA-125 level closely correlates with the volume of the ovary and is not indicative of the underlying pathology . Previous studies found no statistically significant differences when comparing serum CA-125 levels between spontaneous and stimulated cycles or between pregnant and non-pregnant patients . Longitudinal follow-up of patients with sequential determinations of their tumour markers may be helpful for an accurate assessment. During the follow-up of patients with hyper-stimulated ovaries, the serum concentration of the CA-125 tumour marker declines and eventually normalizes. In patients with malignant disease, the serum levels remain elevated or gradually increase.
To overcome the relatively low specificity and sensitivity of risk assessment by a single tumour marker, Moore et al. introduced the ROMA index as an accurate predictive index for ovarian cancer (76.4% sensitivity and 96% specificity) . Our results confirmed that the single biomarker determination of CA-125 was not sufficient to reliable evaluate ovarian malignancy in OHSS. When the combination of CA-125 and HE4 was used, despite the high levels of CA-125, HE4 remained under the reference value and indicated no obvious signs of malignancy. This observation was demonstrated by the low ROMA scores (Table 1).
Epidemiologic follow-up data of infertile patients demonstrates an increased life-long risk for high-grade or borderline malignant ovarian malignancies. However, the exact reason for this increased risk is unclear. Whereas some authors believe it is a result of the infertility itself , others suggest that ovulation induction is associated with cancerogenesis [22, 23]. Although patients undergoing OIT may be at an increased risk of developing ovarian tumours, studies have shown reassuring results in terms of hormone treatment and the incidence of invasive epithelial ovarian cancer . However, exogenous hormone treatment is associated with an increased risk of borderline ovarian malignancy . OIT has not been shown to increase the risk of breast, uterine, or invasive ovarian cancers, although the risk of borderline ovarian tumours might increase . Moreover, the risk of cancer has been shown to be similar in children conceived by artificial reproductive therapies and those conceived naturally . It should also be noted that, due to close medical surveillance, malignancies are overdiagnosed in the female population; this may also augment the early detection of cancers .
Our data suggest that even when the cytological evaluation of ascitic cells obtained in patients diagnosed with OHSS indicates abnormality and possible malignancy, radical surgical intervention is not clinically indicated. Instead, these patients should be closely followed and monitored. If the ovarian size remains abnormal, then the aetiology of the enlargement should be determined by histological sampling via laparoscopy, and the histologist should be informed of the previous OIT. Surgery may still be required for abdominal bleeding, ovarian torsion or rupture, or extra-uterine pregnancy.