First live birth after uterus transplantation in the United States.

Uterus transplantation has proven to be a successful treatment for women with absolute uterine infertility, caused either by the absence of a uterus or the presence of a nonfunctioning uterus. We report the first birth of a healthy child following uterus transplantation in the United States, from a recipient of a uterus allograft procured from an altruistic living donor. Two major modifications from the previously reported live births characterized this uterus transplant. First, the transplanted uterus relied upon and sustained the pregnancy while having only the utero-ovarian vein as venous outflow. The implication is a significantly simplified living donor surgery that paves the way for minimally invasive laparoscopic or robot-assisted techniques for the donor hysterectomy. Second, the time from transplantation to embryo transfer was significantly shortened from prior protocols, allowing for an overall shorter exposure to immunosuppression by the recipient and lowering the risk for potential adverse effects from these medications.

Living Donor Uterus Transplantation: A Single Center's Observations and Lessons Learned From Early Setbacks to Technical Success.

Uterus transplantation is a vascularized composite allograft transplantation. It allows women who do not have a uterus to become pregnant and deliver a baby. In this paper, we analyze the first five cases of living donor uterus transplantation performed in the United States. The first three recipients lost their uterus grafts at days 14, 12, and 6, respectively, after transplant. Vascular complications, related to both inflow and outflow problems, were identified as the primary reason for the graft losses. Two recipients, at 6 and 3 mo, respectively, after transplant, have functioning grafts with regular menstrual cycles. Ultimate success will be claimed only after a live birth. This paper is an in-depth analysis of evaluation, surgical technique, and follow-up of these five living donor uterus transplants. The lessons learned were instrumental in allowing us to evolve from failure to technical and functional success. We aim to share our conclusions and build on knowledge in the evolving field of uterus transplantation.

Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells.

C19 steroids are converted to estrogens by aromatase P450 (P450arom). Aromatase expression in humans is regulated by use of tissue-specific promoters in the placenta (promoter I.1), adipose tissue (promoters I.4, I.3, and II), and gonads (promoter II). The use of each promoter gives rise to a population of P450arom messenger ribonucleic acid (mRNA) species with a unique untranslated 5'-terminus. Aromatase is not expressed in the endometrium of disease-free women. We demonstrated, however, the presence of P450arom mRNA in pelvic endometriotic implants and eutopic endometrial curettings of women with endometriosis. In the current report, aromatase activity and P450arom gene expression were investigated in cultured stromal cells derived from eutopic endometrium and ovarian endometriomas of women with pelvic endometriosis. We also investigated the hormonal regulation of aromatase expression and alternative promoter use in these cells. The effects of interleukin-1 beta (IL-1 beta), IL-2, IL-6, IL-11, oncostatin M, IL-15, tumor necrosis factor-alpha, PGE2, estradiol, R5020, dexamethasone, and dibutyryl cAMP (Bt2cAMP) on aromatase activity in endometriosis-derived stromal cells were assessed. We chose treatments with PGs and ILs because of the inflammatory nature of endometriosis. PGE2 stimulated aromatase activity in endometriosis-derived stromal cells by 19- to 44-fold (37-221 pmol/mg protein-4 h), whereas Bt2cAMP induction was 26- to 60-fold the baseline level. No stimulation was observed by estradiol or R5020 or by IL-1 beta, IL-2, IL-6, IL-11, IL-15, or TNF alpha in the presence or absence of glucocorticoids. A modest induction of aromatase activity (2-fold) was observed in dexamethasone- plus oncostatin M-treated cells. These changes in aromatase activity were accompanied by comparable changes in the levels of P450arom mRNA levels, determined by a quantitative reverse transcription-PCR method. Promoter-specific 5'-ends of P450arom transcripts in total RNA from endometriosis-derived stromal cells treated with PGE2 and Bt2cAMP were amplified employing a novel modified rapid amplification of cDNA5'-ends/Southern hybridization method using exon-specific oligonucleotide probes. The majority of P450arom transcripts in these cells contained the gonadal-type promoter II-specific sequences, whereas very few transcripts contained adipose-type promoter I.3- and I.4-specific sequences. PGE2 appears to be the most potent known stimulator of aromatase in endometriosis. Aromatase expression in PGE2-stimulated stromal cells of endometriosis is regulated primarily by the classically located promoter II, which, in turn, is regulated by cAMP. As PGE2 is known to increase intracellular cAMP levels, estrogen biosynthesis in endometriosis may be primarily regulated by PGE2 that is locally produced. Consequent local estrogen production may promote the growth of endometriotic implants.

Erythropoietin treatment of erythropoietin-deficient anemia without renal disease during pregnancy.

BACKGROUND: The use of recombinant human erythropoietin in pregnancy has been described in patients with renal impairment. We present a patient with a hypoproliferative anemia with low serum erythropoietin levels and no renal disease or other known cause for this type of anemia, who was treated with recombinant human erythropoietin. CASE: A 29-year-old white woman who became pregnant after leuprolide acetate and menopausal gonadotropin therapy developed a moderate anemia (hemoglobin 8.5 g/dL) in early pregnancy. The only important laboratory findings were a hypoproliferative marrow and a low serum erythropoietin level. She was treated successfully with injections of recombinant human erythropoietin. Her pregnancy was otherwise uncomplicated and her pre-delivery hemoglobin level was 12 g/dL. CONCLUSION: Hypoproliferative anemia in pregnancy with low erythropoietin levels and no renal disease can be treated successfully with recombinant human erythropoietin.

Pregnancy rates following tubal anastomosis: Pomeroy partial salpingectomy versus electrocautery.

Eighty-six tubal anastomosis patients were analyzed for successful outcome. Controlling for tubal length, we analyzed a number of possible confounding variables for their effects on pregnancy, including the type of sterilization performed. Results indicated term pregnancies in 63.9% of all patients, with no significant effect seen due to type of sterilization procedure. Monthly fecundity rates and life table analysis similarly demonstrated no significant differences between the two sterilization groups. With the use of multiple logistic regression, only age proved to be a significant predictor of pregnancy (p = 0.008). Type of sterilization as well as other tested variables had no demonstrable effect. We conclude that with careful initial selection of patients, exclusion of women without an anastomosed tube 4 cm or longer, and meticulous surgical technique, successful pregnancy rates higher than those generally quoted can be achieved.

Pronucleus formation following in vitro fertilization of oocytes recovered from a gorilla (Gorilla gorilla gorilla) with unilateral endometrioid adenocarcinoma of the ovary.

A 33-year-old, nonreproductive female gorilla was scheduled for ovariohysterectomy after diagnosing endometrioid adenocarcinoma of the right ovary; the contralateral ovary appeared small and inactive. Follicular recruitment and maturation were stimulated on the left ovary using human menopausal gonadotropin and human chorionic gonadotropin therapy. Three oocytes were recovered and inseminated using a thawed epididymal semen sample collected postmortem and cryopreserved. At 18 h postinsemination, one ovum was fertilized, the second showed evidence of polyspermia, and the third was unfertilized; no further embryonic development was observed. These results demonstrate that viable oocytes can be salvaged from a nonreproductive gorilla using a human exogenous gonadotropin treatment protocol and fertilized in vitro using cryopreserved/thawed epididymal gorilla semen.