Relationship of follicle numbers and estradiol levels to multiple implantation in 3,608 intrauterine insemination cycles.

OBJECTIVE: To determine the relationship of follicle numbers and estradiol (E(2)) levels to multiple implantations in human menopausal gonadotropin (hMG) and clomiphene citrate (CC) cycles. DESIGN: Fifteen-year prospective study. SETTING: Private infertility clinic. PATIENT(S): Women who underwent 3608 cycles of husband or donor intrauterine insemination (IUI). INTERVENTION(S): Ovulation induction (OI) with CC, hMG, or CC+hMG. MAIN OUTCOME MEASURE(S): Pregnancy and multiple implantations. RESULT(S): Triplet and higher-order implantations-but not twin implantations-were related to age, E(2) levels, and number of follicles > or = 12 mm and > or = 15 mm, but not number of follicles > or = 18 mm, in hMG and CC+hMG cycles. For patients less than 35 years old, three or more implantations tripled when six or more follicles were > or = 12 mm, in CC, hMG, and CC+hMG cycles, and when E(2) was > or = 1000 pg mL in hMG and CC+hMG cycles. For patients 35 or older, pregnancy rates in hMG and CC+hMG cycles doubled when six or more follicles were > or = 12 mm, or E(2) levels were >1000 pg mL, whereas 3 or more implantations were not significantly increased. CONCLUSIONS: Withholding hCG or IUI in CC, hMG, and CC+hMG cycles when six or more follicles are > or = 12 mm may reduce triplet and higher-order implantations by 67% without significantly reducing pregnancy rates for patients under 35 years of age.

Expression, localization, and function of transforming growth factor-beta s in embryonic chick spinal cord, hindbrain, and dorsal root ganglia.

We have studied the localizations of transforming growth factor-beta (TGF-beta) 2 and 3 immunohistochemically using isoform-specific antibodies and TGF-beta 3 mRNA by in situ hybridization in the nervous system of the 3- to 15-day-old chick embryo with special reference to spinal cord, hindbrain, and dorsal root ganglia (DRG). At embryonic day (E) 3, TGF-beta 3 mRNA as well as TGF-beta 2 and 3 immunoreactivities (IRs) were most prominent in the notochord, wall of the aorta, and dermomyotome. At E5 and E7, strong TGF-beta 2 and 3 IR were seen in or on radial glia of spinal cord and hindbrain. Radial glia in the floor plate region and ventral commissure gave the most intense signal. In the DRG, fiber strands of intense IRs representing extracellular matrix or satellite cells were seen. Neuronal perikarya did not become IR for TGF-beta 2 and 3 until E11, but even then the moderate signals for TGF-beta 3 mRNA could not be specifically localized to the neuronal cell bodies. In E11 and older embryos, spinal cord glial or glial progenitor cells, but not neuronal cell bodies were labeled for TGF-beta 3 mRNA. Immunocytochemistry and western blot analysis indicated that E8 DRG neurons have the TGF-beta receptor type II, and treatment of these cells with NGF induces expression of TGF-beta 3 mRNA. The TGF-beta isoforms 1, 2, and 3 did not promote survival of E8 DRG neurons in dissociated cell cultures. All three TGF-beta isoforms, however, promoted neurite growth from E8 DRG explants, but were less potent than nerve growth factor. Our data suggest identical localizations of TGF-beta 2 and -beta 3 IR in the developing chick and mammalian nervous systems, underscoring the general importance of TGF-beta s in fundamental events of neural development.

Analogous tamoxifen and estrogen effects on transforming growth factor-betas 1 and 2 in the rat uterus.

Estrogenic stimulation is a potent risk factor for the development of uterine cancer. More recently, analysis of patients in prospective breast cancer trials have established that tamoxifen also increases uterine cancer risk. In this report, uteri of oophorectomized rats were examined to ascertain the effects of estrogen and tamoxifen on the uterine induction of two isoforms of transforming growth factor-beta (TGF-beta). In contrast to studies of cells derived from breast epithelium, our studies reveal that both estrogen and tamoxifen increase immunoreactive TGF-beta. These changes were particularly pronounced in the endometrial stroma. Effects of progesterone also were examined and found to be distinct and relatively restricted to the glandular epithelium. These studies indicate that, in the uteri of oophorectomized rats, tamoxifen exerts estrogen-like effects on a peptide previously implicated in the control of cellular growth and differentiation. We hypothesize that induction of TGF-beta isoforms may be an important mediator of both estrogen- and tamoxifen-induced proliferative disorders in the uterus.