Pregnancy potential and perinatal outcomes of embryos cryopreserved twice: a case-control study.

RESEARCH QUESTION: What are the pregnancy and perinatal outcomes of twice-cryopreserved embryos compared with embryos cryopreserved once? DESIGN: Retrospective register-based case-control study. The case group consisted of transfers of twice-cryopreserved embryos (n = 89), and the control group of transfers of embryos cryopreserved once (n = 304). Matching criteria were embryonic age at transfer and female age category of less than 35 years or 35 and greater. RESULTS: The survival rate of twice-cryopreserved embryos was 92.2%, and 93.7% of the planned frozen embryo transfers (FET) could be completed. FET was performed with cleavage-stage embryos in 17 cases and 68 controls and with blastocysts in 72 cases and 238 controls. The rates of live birth (27.0% versus 31.9%, adjusted odds ratio [OR] 0.70, 95% CI 0.40-1.22, P = 0.21), clinical pregnancy (31.5% versus 36.8%, adjusted OR 0.71, 95% CI 0.42-1.21, P = 0.21) and miscarriage (4.5% versus 3.9%, adjusted OR 1.10, 95% CI 0.33-3.60, P = 0.88) in the case and the control groups were comparable. No difference was seen in the preterm delivery rate (cases 4.2% versus controls 10.3%, P = 0.69). Twenty-five children were born in the case group and 100 in the control group. No difference in birthweight was detected between the groups and there were no large for gestational age fetuses or congenital malformations in the case group. CONCLUSIONS: Uncompromised live birth rates and neonatal outcomes may be expected after the transfer of twice-cryopreserved embryos. To avoid embryo wastage and transfer of multiple embryos, good quality surplus embryos from FET cycles may be cryopreserved again by vitrification.

Roles of human epididymis protein 4, carbohydrate antigen 125, inhibin B and anti-Müllerian hormone in the differential diagnosis and follow-up of ovarian granulosa cell tumors.

OBJECTIVE: Evaluation of circulating tumor markers in ovarian cancer is crucial for optimal patient care. The goal of this study was to verify the most accurate circulating tumor markers for the diagnosis and follow-up of adult-type granulosa cell tumors (AGCTs). METHODS: The levels of circulating human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125), together with AGCT markers inhibin B and anti-Müllerian hormone (AMH), were measured in 135 samples from AGCT patients, 37 epithelial ovarian carcinoma (EOC) patients, and 40 endometrioma (ENDO) patients. The levels were plotted with receiver operating characteristic (ROC) graphs, and the area under the curves (AUC) of the different markers were calculated and compared. RESULTS: HE4 levels were significantly lower in AGCTs than in EOCs (p<0.0001). CA125 levels were above 35IU/l in 25% of AGCT patients and 47.5% of ENDO patients, whereas inhibin B and AMH levels were elevated only in patients with AGCTs. In the AUC comparison analyses, inhibin B alone was sufficient to differentiate AGCT from EOC. In differentiating AGCT from ENDO, inhibin B and AMH performed similarly, and the combination of inhibin B and AMH increased the accuracy compared to either marker alone (sensitivity, 100%; specificity, 93%). Among AGCT patients, inhibin B was the best marker for detecting the presence of AGCT. CONCLUSIONS: HE4 and CA125 levels were low in AGCTs, and inhibin B was the most accurate circulating biomarker in distinguishing AGCTs from EOCs and from ENDOs. Inhibin B was also the best single marker for AGCT follow-up.

Serum concentrations of HE4 change little during in vitro fertilization.

OBJECTIVE: Human epididymal secretory protein 4 (HE4) is a biomarker for ovarian cancer. The effect of follicle stimulating hormone (FSH) stimulation during in vitro fertilization (IVF) on HE4 was evaluated to determine whether substantial hormonal stimulation of the ovaries affects the serum levels of this marker. Findings were compared with serum concentrations of cancer antigen 125 (CA125), currently the most commonly used marker for ovarian cancer. DESIGN: Prospective cohort study. SETTING: University hospital infertility clinic. POPULATION: Infertility patients undergoing IVF treatment. METHODS: We determined the serum concentration of HE4 and CA125 in serial blood samples in 20 women treated with IVF. Samples were taken following gonadotrophin-releasing hormone agonist suppression, two to three times during FSH stimulation, at ovum pick-up and 2 weeks following embryo transfer at the time of the pregnancy test. Ovarian follicles were counted and serum estradiol concentrations measured throughout treatment. MAIN OUTCOME MEASURES: Serum HE4, CA125 and estradiol concentrations. RESULTS: Serum HE4 levels did not increase significantly during the FSH stimulation. The majority of values remained below the normal reference range (<70 pm) throughout the treatment. Serum CA125 concentration also remained low during stimulation. Serum estradiol concentration reflected the severity of ovarian stimulation during IVF, increasing 3.9-fold with stimulation. CONCLUSIONS: Serum HE4 concentrations respond little if at all to supraphysiological ovarian stimulation, suggesting that the amount of circulating HE4 in women with normal ovaries is independent of gonadotropin stimulation. Hormonal stimulation of the ovaries is unlikely to affect the differential diagnosis of ovarian tumors with HE4.