Ovarian stimulation and liver dysfunction: Is a clinical relationship possible? A case of hepatic failure after repeated cycles of ovarian stimulation
A 35-year-old nulliparous woman was admitted at 32 weeks of gestation to our obstetric emergency room for hypertensive crisis (240/140 mm Hg). She had been subjected to four cycles of COS for IUI. She had not any risk factors for pre-eclampsia. The first cycle of 150 IU/day recombinant FSH (Fostimon, IBSA Institut Biochimique SA, Lugano, Switzerland) was interrupted by the onset of moderate OHSS. The next two cycles with 75 IU/day recombinant FSH were not successful. During the fourth COS the patient received a total dose of 750 IU of r-FSH; the triggering of ovulation was performed by 10,000 IU of HCG (Gonasi HP, IBSA Institut Biochimique SA) and after 36 hours IUI was performed. After this cycle, a pregnancy began and its course was regular until the third trimester (last visit at the 27th week of gestation). At admission, she reported general malaise and non-specific abdominal pain. She was immediately treated with 10 mg of nifedipine sublingually; a reduction in blood pressure was achieved even though it remained high (180/100 mm Hg). Blood samples showed hyperuricemia (uric acid, 5.8 mg/dL) and hypertransaminasemia (alanine transaminase [ALT], 137 IU/L, lactate dehydrogenase [LDH], 870 IU/L). A urine sample showed proteinuria. An obstetric ultrasound examination showed oligohydramnios, severe foetal growth restriction, and flowmetry changes (absent umbilical artery end-diastolic flow). The cardiotocographic control revealed reduced short-term variability and absence of episodes of high variation. Based on the clinical symptoms of the patient, we decided to perform emergency Caesarean section (CS) without waiting for respiratory distress syndrome prophylaxis. The female newborn (1,050 g) had an Apgar score of 7 at the first minute and 9 at the fifth minute. Immediately after the CS, the patient was considerably relieved and the blood pressure stabilized (140/85 mm Hg). After about 3 hours, the patient complained of acute right upper quadrant pain. Pressure values decreased rapidly. Blood tests revealed severe anaemia and disseminated intravascular coagulation (DIC). An explorative laparotomy was immediately performed and hemoperitoneum was noted (about 1,050 mL of fresh blood were aspirated). The uterus was flabby, purple, and bleeding; thus we decided to perform a total hysterectomy. A mid-line xifo-pubic abdominal incision was performed to explore the superior abdomen and the surgeon identified a large laceration of Glisson's capsule causing an active and massive haemorrhage. Good haemostasis was not achievable because the liver was oedematous. Thus packing was performed by three large gauze packs to compress the bleeding lesions and two supra and underhepatic drains were left in the abdomen. Post surgery, the clinical situation worsened despite the efforts to stabilize the blood coagulation parameters. The day after the first surgical operation, laboratory findings showed an increase in liver enzymes (aspartate aminotransferase, 3,045 U/L; ALT, 2,532 U/L; LDH, 5,814 U/LE), low levels of haemoglobin (5.5 g/dL), haematocrit (16%), and platelets (35×103/µL), and a low glomerular filtration rate (18 mL/mL). A second laparotomy was necessary. This second attempt at haemostasis was successful, but liver function was already impaired. Therefore, the patient was placed on a waiting list for liver transplant; about 24 hours later an appropriate organ became available and a liver transplantation was carried out. The patient's condition seemed to improve, but in the following day a complication occurred that caused death from sepsis.