Value of estradiol response after human chorionic gonadotropin administration in predicting in vitro fertilization success.

OBJECTIVE: To determine whether the serum E2 response after the administration of exogenous hCG is predictive of outcome during IVF. DESIGN: Prospective, noncomparative cohort. SETTING: Two academic centers and one private-practice IVF program. PATIENT(S): Two hundred twenty-two couples undergoing IVF for infertility arising from ovarian dysfunction, asthenoteratospermia, endometriosis, tubal disease, or unexplained infertility. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and miscarriage rates were compared in cycles that demonstrated an increase, decrease, or plateau in the serum E2 level on the day after hCG administration. The effects of age, cause of infertility, and maximum E2 value on outcome were evaluated. RESULT(S): Ninety-two cycles resulted in a clinical pregnancy and 130 cycles failed. Of 115 cycles in which the E2 level rose, 42 (37%) resulted in an ongoing pregnancy; among cycles with plateauing E2 responses, 20 of 69 (29%) resulted in a pregnancy. Fifteen of 38 (39%) of cycles exhibiting a drop in serum E2 resulted in an ongoing pregnancy. No statistically significant differences in ongoing pregnancy rates were noted in the increasing, plateauing, or decreasing E2 response groups. CONCLUSION(S): E2 values obtained on the day after hCG administration are not predictive of outcome in women undergoing IVF.

Epidermal growth factor ameliorates autosomal recessive polycystic kidney disease in mice.

C57BL/6J mice homozygous for the cpk gene exhibit an autosomal recessive (AR) form of polycystic kidney disease (PKD), similar to human ARPKD, with massive collecting duct cysts. These cysts are lined by epithelial with an immature phenotype. Since renal expression of epidermal growth factor (EGF) is also significantly decreased in affected mice, we hypothesized that renal EGF is necessary for normal developmental maturation of the collecting duct. To determine if the lack of EGF may be a decisive factor in the initiation and/or growth of collecting duct cysts, we administered exogenous EGF (1 microgram/g body wt subcutaneously) daily for Postnatal Days 3-9 (a critical period for collecting duct maturation) to C57BL/6J-cpk mice. EGF but not sham or albumin treatment retarded the development of PKD, reduced the degree of renal failure associated with the disease, and prolonged the survival of cystic mice. Sulfated glycoprotein-2 gene expression, a marker of immaturity in collecting duct cells, was reduced in cystic kidney by EGF treatment. This finding indicates that EGF treatment was associated with an increase in the maturation of the collecting duct epithelial cells. These findings support the view that decreased EGF may play a significant role in promoting the enlargement of collecting duct cysts in a hereditary model of ARPKD and that PKD involves defective and/or arrested collecting duct cell maturation.

Renal cysts in transgenic mice expressing transforming growth factor-alpha.

Transforming growth factor-alpha (TGF-alpha) is a member of the epidermal growth factor (EGF) family of proteins and, like EGF, elicits its cellular function by binding to the EGF receptor. EGF stimulation may have a role in several normal and pathologic processes in the kidney, and EGF has been implicated in the development of renal cysts in vitro and in human autosomal dominant polycystic kidney disease. We sought to determine whether renal expression of an EGF-like protein (TGF-alpha) could lead to the formation of renal cysts in vivo. We examined morphologic alterations to the normal kidney caused by renal expression of a TGF-alpha transgene linked to a mouse metallothionein promoter stably integrated into the genome of the CD1 mouse. TGF-alpha transgene expression was induced with exogenous zinc treatment starting at 4 weeks of age, and mice were killed at 8 weeks of age. The transgene was expressed at higher levels in female transgenic mice than in male transgenic mice. The augmented expression of the TGF-alpha transgene in females was associated with increased renal size and the development of renal epithelial cysts. Both male and female mice exhibited increases in glomerular size and mesangial volume density. These results provide evidence that stimulation by an endogenous EGF-like protein can lead to renal enlargement, glomerular mesangial expansion, and renal cyst formation.