Role of adjuvant therapy in intermediate-risk cervical cancer patients - Subanalyses of the SCCAN study.

OBJECTIVE: The "intermediate-risk" (IR) group of early-stage cervical cancer patients is characterized by negative pelvic lymph nodes and a combination of tumor-related prognostic risk factors such as tumor size ≥2 cm, lymphovascular space invasion (LVSI), and deep stromal invasion. However, the role of adjuvant treatment in these patients remains controversial. We investigated whether adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with IR cervical cancer. METHODS: We analyzed data from patients with IR cervical cancer (tumor size 2-4 cm plus LVSI OR tumor size >4 cm; N0; no parametrial invasion; clear surgical margins) who underwent primary curative-intent surgery between 2007 and 2016 and were retrospectively registered in the international multicenter Surveillance in Cervical CANcer (SCCAN) study. RESULTS: Of 692 analyzed patients, 274 (39.6%) received no adjuvant treatment (AT-) and 418 (60.4%) received radiotherapy or chemoradiotherapy (AT+). The 5-year disease-free survival (83.2% and 80.3%; PDFS = 0.365) and overall survival (88.7% and 89.0%; POS = 0.281) were not significantly different between the AT- and AT+ groups, respectively. Adjuvant (chemo)radiotherapy was not associated with a survival benefit after adjusting for confounding factors by case-control propensity score matching or in subgroup analyses of patients with tumor size ≥4 cm and <4 cm. In univariable analysis, adjuvant (chemo)radiotherapy was not identified as a prognostic factor in any of the subgroups (full cohort: PDFS = 0.365; POS = 0.282). CONCLUSION: Among patients with IR early-stage cervical cancer, radical surgery alone achieved equal disease-free and overall survival rates to those achieved by combining radical surgery with adjuvant (chemo)radiotherapy.

The prognostic value of squamous differentiation in endometrioid type endometrial cancer: a matched analysis.

We aimed to examine the effect of the squamous differentiation on survival outcomes of women with endometrioid adenocarcinoma. We retrospectively reviewed the patients with endometrioid adenocarcinoma who underwent primary surgical treatment in a tertiary referral hospital. Sixty-nine patients having squamous differentiation constituted the case group. Each woman in the case group was matched with two patients in the control group based on age, disease stage, tumour grade, lymphovascular space invasion, tumour size, myometrial invasion, type of surgery and adjuvant therapy. During the follow-up, the recurrence rates were similar between the case (5/69, 7.2%) and control (10/138, 7.2%) groups (p = 1.0). The 5-year disease-free survival rate was 90.2% for the case group and 88.6% for the control group (p = .51). The 5-year overall survival rate was 94.6% for the case group and 91.8% for the control group (p = .12). Squamous differentiation seems to have no impact on the prognosis of patients with endometrioid adenocarcinoma.IMPACT STATEMENTWhat is already known on this subject? A focus of squamous differentiation is recognised in 12.8-25% of women with endometrioid adenocarcinoma. The prognostic value of the squamous differentiation was evaluated in several previous studies. However, it could not be clarified due to the conflicting results of these studies.What do the results of this study add? The probable confounding effects of well-known prognostic factors including age at diagnosis, International Federation of Gynaecology and Obstetrics stage, tumour grade, lymphovascular space invasion, tumour size, myometrial invasion, type of surgery and adjuvant therapy were eliminated with the case-control study design in the current study. Our findings indicate that the presence of squamous differentiation does not have any prognostic effect in endometrioid type endometrial cancer.What are the implications of these findings for clinical practice and/or further research? The molecular prognosticators of endometrial cancer were extensively studied in recent years. It is likely that clinicopathological and molecular prognostic factors will be integrated for predicting prognosis as a part of routine clinical practice soon. In this context, the prognostic value of the squamous differentiation in endometrioid adenocarcinomas may further be clarified by larger and multicentric studies that utilise central pathology review.

Prognostic value of the number of the metastatic lymph nodes in locally early-stage cervical cancer: squamous cell carcinoma versus non-squamous cell carcinoma.

PURPOSE: To clarify the prognostic value of the number of metastatic lymph nodes (mLNs) in squamous and non-squamous histologies among women with node-positive cervical cancer. METHODS: One hundred ninety-one node-positive cervical cancer patients who had undergone radical hysterectomy plus systematic pelvic and para-aortic lymphadenectomy followed by concurrent radiochemotherapy were retrospectively reviewed. The prognostic value of the number of mLNs was investigated in squamous cell carcinoma (SCC) v (n = 148) and non-SCC (n = 43) histologies separately with univariate log-rank test and multivariate Cox regression analyses. RESULTS: In SCC cohort, mLNs > 2 was significantly associated with decreased 5-year disease-free survival (DFS) [hazard ratio (HR) = 2.06; 95% confidence interval (CI) 1.03-4.09; p = 0.03) and overall survival (OS) (HR = 2.35, 95% CI 1.11-4.99; p = 0.02). However mLNs > 2 had no significant impact on 5-year DFS and 5-year OS rates in non-SCC cohort (p = 0.94 and p = 0.94, respectively). We stratified the entire study population as SCC with mLNs ≤ 2, SCC with mLNs > 2, and non-SCC groups. Thereafter, we compared survival outcomes. The non-SCC group had worse 5-year OS (46.8% vs. 85.3%, respectively; p < 0.001) and 5-year DFS rates (31.6% vs. 82.2%, respectively; p < 0.001) when compared to those of the SCC group with mLNs ≤ 2. However, the non-SCC group and the SCC group with mLNs > 2 had similar 5-year OS (46.8% vs. 65.5%, respectively; p = 0.16) and 5-year DFS rates (31.6% vs. 57.5%, respectively; p = 0.06). CONCLUSION: Node-positive cervical cancer patients who have non-SCC histology as well as those who have SCC histology with mLNs > 2 seem to have worse survival outcomes when compared to women who have SCC histology with mLNs ≤ 2.

Perioperative SARS-CoV-2 infection among women undergoing major gynecologic cancer surgery in the COVID-19 era: A nationwide, cohort study from Turkey.

OBJECTIVE: The objective of this study was to determine the rate of perioperative SARS-CoV-2 infection among gynecologic cancer patients undergoing major surgery. METHODS: The database of the Turkish Ministry of Health was searched in order to identify all consecutive gynecologic cancer patients undergoing major surgery between March 11, 2020 and April 30, 2020 for this retrospective, nationwide, cohort study. The inclusion criteria were strictly founded on a final histopathological diagnosis of a malignant gynecologic tumor. COVID-19 cases were diagnosed by reverse transcriptase- polymerase chain reaction testing for SARS-CoV-2. The rate of perioperative SARS-CoV-2 infection and the 30-day mortality rate of COVID-19 patients were investigated. RESULTS: During the study period, 688 women with gynecologic cancer undergoing major surgery were identified nationwide. The median age of the patients was 59 years. Most of the surgeries were open (634/688, 92.2%). There were 410 (59.6%) women with endometrial cancer, 195 (28.3%) with ovarian cancer, 66 (9.6%) with cervical cancer, 14 (2.0%) with vulvar cancer and 3 (0.4%) with uterine sarcoma. The rate of SARS-CoV-2 infections confirmed within 7 days before or 30 days after surgery was 46/688 (6.7%). All but one woman was diagnosed postoperatively (45/46, 97.8%). The rates of intensive care unit admission and invasive mechanical ventilation were 4/46 (8.7%) and 2/46 (4.3%), respectively. The 30-day mortality rate was 0%. CONCLUSION: In the COVID-19 era, gynecologic cancer surgery may be performed with an acceptable rate of perioperative SARS-CoV-2 infection if the staff and the patients strictly adhere to the established infection control measures.

Does lymph node ratio have any prognostic significance in maximally cytoreduced node-positive low-grade serous ovarian carcinoma?

PURPOSE: To determine the prognostic impact of the lymph node ratio (LNR) in node-positive low-grade serous ovarian cancer (LGSOC). METHODS: We retrospectively reviewed women with LGSOC who had undergone maximal cytoreduction followed by standard chemotherapy in 11 centers from Turkey during a study period of 20 years. Sixty two women with node-positive LGSOC were identified. LNR was defined as the number of metastatic lymph nodes (LNs) divided by the number of total LNs removed. We grouped patients pursuant to the LNR as LNR ≤ 0.09 and LNR > 0.09. The prognostic value of LNR was investigated by employing the univariate log-rank test and multivariate Cox-regression model. RESULTS: With a median follow-up of 45 months, the 5-year progression-free survival (PFS) rates were 61.7% for women with LNR ≤ 0.09 and 32.0% for those with LNR > 0.09 (p = 0.046) whereas, the 5-year overall survival (OS) rates were 72.8% for LNR ≤ 0.09 and 54.7% for LNR > 0.09 (p = 0.043). On multivariate analyses, lymphovascular space invasion (LVSI) (Hazard Ratio [HR] 4.18, 95% confidence interval [CI] 1.88-9.27; p < 0.001), omental involvement (HR 3.48, 95% CI 1.36-8.84; p = 0.009) and LNR > 0.09 (HR 3.51, 95% CI 1.54-8.03; p = 0.003) were adverse prognostic factors for PFS. Additionally, LVSI (HR 6.56, 95% CI 2.33-18.41; p < 0.001), omental involvement (HR 6.34, 95% CI 1.86-21.57; p = 0.003) and LNR > 0.09 (HR 7.20, 95% CI 2.33-22.26; p = 0.001) were independent prognostic factors for decreased OS. CONCLUSION: LNR > 0.09 seems to be an independent prognosticator for decreased survival outcomes in LGSOC patients who received maximal cytoreduction followed by standard adjuvant chemotherapy.

Comparison of HE 4, CA 125, ROMA score and ultrasound score in the differential diagnosis of ovarian masses.

OBJECTIVE: To compare the value of ultrasonography (USG) score, cancer antigen 125 (CA 125), human epididymis protein 4 (HE 4) and risk of malignancy algorithm (ROMA) in differential diagnosis ovarian masses. METHODS: This prospective study was conducted between May 2012 and September 2013 in a single center. Eighty-four women who had an ovarian mass on imaging and underwent surgery were included. The diagnostic performances of CA 125, HE 4, ROMA score and USG score for ovarian cancer were analyzed. RESULTS: There were 65 (77.3 %) women with benign ovarian tumors and 19 (22.7 %) women with malignant ovarian tumors. According to receiver operating characteristic (ROC) analysis; area under curve (AUC) was 0.874 for the USG score (p < 0.001), 0.794 for the CA 125 (p < 0.001), 0.9 for the HE 4 (p < 0.001), and 0.893 for the ROMA (p < 0.001). The USG score ≥ 3 had a sensitivity of 68.4 % and specificity of 90.7 %.The CA 125 ≥ 35 IU/l, had a sensitivity of 84.2 %, specificity of 49.2 %, the HE 4 ≥ 150 pM, had a sensitivity of 84.2 %, specificity of 98.4 % and the ROMA score had a sensitivity of 84.2 %, specificity of 75.3 % CONCLUSION: The HE 4 had higher accuracy than ROMA score, USG score and CA 125, in predicting ovarian cancer. Besides, the USG score was a simple and achievable method with acceptable performance.

Coexistence of uterine adenomyosis is not associated with a better prognosis in endometrioid-type endometrial cancer.

BACKGROUND: Prognostic value of accompanying adenomyosis in endometrial cancer is the subject of interest due to their common etiology and co-occurrence frequency. However, it is still unclear whether adenomyosis has a role in the prognosis of endometrial cancer. AIMS: The aim of this study was to determine the effects of adenomyosis on the prognosis of patients with endometrial cancer. METHODS: In this study, medical records of 552 patients with endometrioid endometrial cancer who underwent surgery between 2007 and 2017 were retrospectively reviewed. The patients were divided into two groups based on the presence or absence of adenomyosis, and these two groups were compared in terms of the clinicopathological factors and survival outcomes of patients. RESULTS: Of these patients, 103 (18.7%) had adenomyosis, and the remaining 449 (81.3%) did not. The endometrial cancer patients with adenomyosis exhibited earlier stages (p < 0.001), lower tumor grades (p < 0.001), tumor sizes ≤ 2 cm (p = 0.002), myometrial invasion < 50% (p < 0.001), and negative lymphovascular space invasion (p < 0.001). The 5-year overall survival rate was comparable between the adenomyosis and non-adenomyosis groups (95 vs. 89.1%, respectively; p = 0.085). The presence of adenomyosis was significantly associated with a higher 5-year disease-free survival rate (95.1 vs. 87.9%; p = 0.047), but adenomyosis did not remain as a prognostic factor in multivariate analysis. CONCLUSION: The results of our study showed that the endometrioid endometrial cancer patients with adenomyosis are significantly associated with smaller tumor sizes, less myometrial invasion, lower tumor grades, less lymphovascular space invasion, and earlier FIGO stages. Nevertheless, adenomyosis was not found to be an independent prognostic factor for endometrioid endometrial cancer.

Is It Possible to Develop a Prediction Model for Lymphovascular Space Invasion in Endometrioid Endometrial Cancer?

OBJECTIVE: The purpose of this retrospective study was to define a risk index that would serve as a surrogate marker of lymphovascular space invasion (LVSI) in women with endometrioid endometrial cancer (EC). MATERIALS AND METHODS: Final pathology reports of 498 women who underwent surgery with curative intent for endometrioid EC between January 2008 and June 2018 were retrospectively reviewed. Logistic regression was used to investigate clinicopathologic factors associated with positive LVSI status. Independent risk factors for LVSI were used to build a risk model and "risk of LVSI index" was defined as "tumor grade×primary tumor diameter×percentage of myometrium involved." The scores used in the "risk of LVSI index" were weighted according to the odds ratios assigned for each variable. The risk of LVSI index was noted for each patient. The diagnostic performance of the model was expressed as sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. RESULTS: According to the "risk of LVSI index," presence of LVSI was correctly estimated in 89 of 104 LVSI-positive women at a cutoff of 161.0 (sensitivity 85.5%, specificity 79.4%, negative predictive value 95.4%, positive predictive value 52.3%, positive likelihood ratio 4.15, negative likelihood ratio 0.18). The area under curve of the receiver-operating characteristics was 0.90 (95% confidence interval, 0.87-0.93) at this cutoff. CONCLUSIONS: It seems possible to predict the presence of LVSI in women with endometrioid EC when the "risk of LVSI index" is calculated. However, external validation of this model is warranted.

The prognostic value of lymph node ratio in stage IIIC cervical cancer patients triaged to primary treatment by radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy.

OBJECTIVE: The aim of this study was to determine the prognostic value of lymph node ratio (LNR) in women with 2018 International Federation of Gynecology and Obstetrics stage IIIC cervical cancer. METHODS: In this retrospective dual-institutional study, a total of 185 node-positive cervical cancer patients who had undergone radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy were included. All of the patients received adjuvant chemoradiation after surgery. LNR was defined as the ratio of positive lymph nodes (LNs) to the total number of LNs removed. The patients were categorized into 2 groups according to LNR; LNR <0.05 and LNR ≥0.05. The prognostic value of LNR was evaluated with univariate log-rank tests and multivariate Cox regression models. RESULTS: A total of 138 patients (74.6%) had stage IIIC1 disease and 47 (25.4%) patients had stage IIIC2 disease. With a median follow-up period of 45.5 months (range 3-135 months), the 5-year disease-free survival (DFS) rate was 62.5% whereas the 5-year overall survival (OS) rate was 70.4% for the entire study population. The 5-year DFS rates for LNR <0.05 and LNR ≥0.05 were 78.2%, and 48.4%, respectively (p<0.001). Additionally, the 5-year OS rates for LNR <0.05 and LNR ≥0.05 were 80.6%, and 61.2%, respectively (p=0.007). On multivariate analysis, LNR ≥0.05 was associated with a worse DFS (hazard ratio [HR]=2.12; 95% confidence interval [CI]=1.15-3.90; p=0.015) and OS (HR=1.95; 95% CI=1.01-3.77; p=0.046) in women with stage IIIC cervical cancer. CONCLUSIONS: LNR ≥0.05 seems to be an independent prognostic factor for decreased DFS and OS in stage IIIC cervical carcinoma.

SATEN III-Splitting Adjuvant Treatment of stage III ENdometrial cancers: an international, multicenter study.

INTRODUCTION: The purposes of this study were to compare adjuvant treatment modalities and to determine prognostic factors in stage III endometrioid endometrial cancer (EC). METHODS: SATEN III was a retrospective study involving 13 centers from 10 countries. Patients who had been operated on between 1998 and 2018 and diagnosed with stage III endometrioid EC were analyzed. RESULTS: A total of 990 women were identified; 317 with stage IIIA, 18 with stage IIIB, and 655 with stage IIIC diseases. The median follow-up was 42 months. The 5-year disease-free survival (DFS) of patients with stage III EC by adjuvant treatment modality was 68.5% for radiotherapy (RT), 54.6% for chemotherapy (CT), and 69.4% for chemoradiation (CRT) (p=0.11). The 5-year overall survival (OS) for those patients was 75.6% for RT, 75% for CT, and 80.7% for CRT (p=0.48). For patients with stage IIIA disease treated by RT versus CT versus CRT, the 5-year OS rates were 75.6%, 75.0%, and 80.7%, respectively (p=0.48). Negative peritoneal cytology (HR: 0.45, 95% CI: 0.23 to 0.86; p=0.02) and performance of lymphadenectomy (HR: 0.33, 95% CI: 0.16 to 0.77, p=0.001) were independent predictors for improved OS for stage IIIA EC. For women with stage IIIC EC treated by RT, CT, and CRT, the 5-year OS rates were 78.9%, 67.0%, and 69.8%, respectively (p=0.08). Independent prognostic factors for better OS for stage IIIC disease were age <60 (HR: 0.50, 95%CI: 0.36 to 0.69, p<0.001), grade 1 or 2 disease (HR: 0.59, 95% CI: 0.37 to 0.94, p=0.014; and HR: 0.65, 95%CI: 0.46 to 0.91, p=0.014, respectively), absence of cervical stromal involvement (HR: 063, 95% CI: 0.46 to 0.86, p=0.004) and performance of para-aortic lymphadenectomy (HR: 0.52, 95% CI: 0.35 to 0.72, p<0.001). DISCUSSION: Although not statistically significant, CRT seemed to be a better adjuvant treatment option for stage IIIA endometrioid EC. Systematic lymphadenectomy seemed to improve survival outcomes in stage III endometrioid EC.

A novel multivariable prediction model for lymphatic dissemination in endometrioid endometrial cancer: The lymph node Metastasis Risk Index.

OBJECTIVE: The purpose of this study was to develop a risk assessment index that could determine which endometrioid endometrial cancer (EC) patients would benefit from a lymphadenectomy. METHODS: The final pathology reports of 353 women who underwent complete surgical staging, including pelvic and para-aortic lymphadenectomy, for endometrioid EC between January 2008 and June 2018 were retrospectively reviewed. A logistic regression was used to investigate the clinicopathological factors associated with a positive nodal status. The independent risk factors for lymphatic dissemination were used to build a risk model and a "Lymph Node (LN) Metastasis Risk Index" was defined as follows: (tumor grade) × (primary tumor diameter) × (percentage of myometrial invasion) × (preoperative serum CA 125 level). The scores used in the LN Metastasis Risk Index were weighted according to the odds ratios assigned for each variable. The diagnostic performance of the model was expressed as the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. RESULTS: The LN Metastasis Risk Index correctly identified 35 of 40 LN-positive women at a cutoff point of 981.0 (sensitivity: 87.5%, specificity: 86.3%, negative predictive value: 98.2%, positive predictive value: 44.9%, positive likelihood ratio: 6.37, and negative likelihood ratio: 0.14). The area under the receiver operating characteristic curve was 0.90 (95% confidence interval = 0.858-0.947) at this cutoff. The clinical accuracy of the model was 86.4%. When a cutoff point of <981.0 was selected in order to define those women at low-risk for lymphatic dissemination, our prediction model classified 275 women (77.9%) as being at low-risk for nodal involvement. Among these 275 women, 5 actually had positive LNs, which indicated a 1.8% false-negative rate. CONCLUSION: After external validation, the LN Metastasis Risk Index may be a valuable tool for the surgical management of endometrioid EC.

Is the revised 2018 FIGO staging system for cervical cancer more prognostic than the 2009 FIGO staging system for women previously staged as IB disease?

OBJECTIVE: The purpose of this study was to compare the prognostic value of the revised FIGO staging system with that of the 2009 FIGO staging system for women previously staged as IB disease. METHODS: Institutional cervical cancer databases of two high-volume gynecologic cancer centers in Ankara, Turkey, were retrospectively analyzed. Only women with 2009 FIGO stage IB1 or IB2 disease who underwent primary surgery were included. Survival curves were generated using Kaplan-Meier plots, and the log-rank test was used for survival comparisons. The Cox proportional hazards regression model was used to obtain hazard ratios (HRs) and 95% confidence interval (CI). RESULTS: Data from 425 women were analyzed. The 2009 FIGO stage IB2 (n = 131) disease was associated with a nearly three-fold increased risk of mortality when compared to the 2009 FIGO stage IB1 (n = 294) disease (HR: 2.72, 95% CI: 1.69-4.37; p < 0.001). Stage migration was observed in 372 (87.5%) patients, according to the revised FIGO staging system, leading to no significant difference in five-year overall survival rates between stage IB1 (n=53) and IB2 (n=127) disease (95.2% vs. 89.3%, respectively; p = 0.23),or between stage IB2 (n=127) and IB3 (n=95) disease (89.3% vs. 84.2%, respectively; p = 0.12). Similarly, there was no significant difference in five-year overall survival rates between stage IIIC1 (n=114) and IIIC2 (n=36) disease (79.0% vs. 67.2%, respectively; p = 0.34). CONCLUSION: When compared to the 2009 FIGO staging system, the revised staging system has more sub-stages, which leads to fewer patients in each sub-stage, resulting in diminished statistical power.

Para-aortic lymph node involvement revisited in the light of the revised 2018 FIGO staging system for cervical cancer.

OBJECTIVE: This dual-institutional, retrospective study aimed to determine the clinicopathological risk factors for para-aortic lymph node (LN) metastasis among women who underwent radical hysterectomy with systematic pelvic and para-aortic lymphadenectomy for 2009 FIGO stage IB1-IIA2 cervical cancer. METHODS: Institutional cervical cancer databases of two high-volume gynecologic cancer centers in Ankara, Turkey were retrospectively analyzed. Women with 2009 FIGO stage IB1-IIA2 cervical cancer that had undergone radical hysterectomy with pelvic and para-aortic lymphadenectomy between January 2006 and December 2018 were included in the study. Patient data were analyzed with respect to para-aortic LN involvement and all potential clinicopathological risk factors for para-aortic LN metastasis were investigated. RESULTS: A total of 522 women met the inclusion criteria. Pelvic LN metastasis was detected in 190 patients (36.4%), para-aortic LN metastasis in 48 patients (9.2%), isolated para-aortic LN metastasis in 4 (0.8%), and both pelvic and para-aortic LN metastasis in 44 (8.4%) women, respectively. The independent risk factors identified for para-aortic LN involvement included parametrial invasion (odds ratio [OR]: 3.57, 95% confidence interval [CI]: 1.65-7.72; p = 0.001), metastasized pelvic LN size > 1 cm (OR: 4.51, 95% CI: 1.75-11.64; p = 0.002), multiple pelvic LN metastases (OR: 3.83, 95% CI: 1.46-10.01; p = 0.006), and common iliac LN metastasis (OR: 2.97, 95% CI: 1.01-8.68; p = 0.04). A total of 196 (37.5%) patients exhibited at least one risk factor for para-aortic nodal disease. CONCLUSION: Parametrial invasion, metastasized pelvic LN size > 1 cm, multiple pelvic LN metastases, and common iliac LN metastasis seem to be independent predictors of para-aortic LN involvement.

Two cases of first onset intrahepatic cholestasis of pregnancy associated with moderate ovarian hyperstimulation syndrome after IVF treatment and review of the literature.

Intrahepatic cholestasis of pregnancy (ICP) is an uncommon disorder, which generally occurs in the second and third trimester of pregnancy with symptoms of pruritus. The cause of ICP is unknown but genetic, hormonal and environmental factors contribute to its pathogenesis. The aetiology of ICP is unclear but elevation in oestrogen levels thought to cause ICP is typically seen in the third trimester of pregnancy, and for this reason it is not usually considered in the differential diagnosis of pruritus and liver function disorders in the first trimester of the pregnancy. We present two cases of pregnancy after IVF treatment diagnosed with ICP following the development of OHSS, deteriorating liver function tests and severe pruritus.