No guarantees: planned oocyte cryopreservation, not quite an insurance policy.

Planned oocyte cryopreservation (OC) has the potential to address the burden of the biological clock, giving women and individuals with ovaries more autonomy in choosing when to have children and with whom. In the United States, the annual number of OC cycles has grown significantly, yet many questions remain regarding planned OC. The field is starting to gather data on the clinical practice and social perspectives around planned oocyte cryopreservation, including the optimal age range at which to offer planned OC, what factors are most predictive of a successful outcome, and the optimal number of oocytes and ovarian stimulation cycles to achieve a live birth. There is a clear need for setting realistic expectations about the chance of success with OC; however, most patients have yet to return to thaw their oocytes, and outcomes data are limited. Clinical models have been developed to predict OC success based on surrogate markers such as age, number of oocytes retrieved, and anti-Müllerian hormone level. Patient education should emphasize the age-related decline in fertility, that eggs do not equal embryos, and that more than one cycle may be needed to obtain sufficient oocytes to have a reasonable chance of future success. While planned OC is not quite an insurance policy against future reproductive challenges, it provides the best option to date for expanding the reproductive window and maximizing reproductive options while navigating individual life circumstances in the context of family building.

Association between secondary infertility and fallopian tube obstruction on hysterosalpingography.

OBJECTIVE: To determine whether women with secondary infertility have a lower prevalence of tubal pathology as evidenced by hysterosalpingographic (HSG) analysis. STUDY DESIGN: A cross-sectional study was performed on 551 women seen for evaluation of infertility at an academic medical center. Each patient's chart was reviewed for the presence of primary vs. secondary infertility. History of sexually transmitted infection, prior surgery and details of prior pregnancies were recorded. HSG reports and films were evaluated for evidence of tubal disease. RESULTS: Controlling for 5-year age category, history of sexually transmitted disease and history of surgery, the adjusted risk ratio for abnormal HSG in women with secondary vs. primary infertility was 1.75 (95% CI 1.16-2.64). Among patients with secondary infertility, there was no difference between mode of delivery in the prior pregnancy (vaginal vs. cesarean delivery) and abnormal HSG. CONCLUSION: In the population we studied, accounting for confounding variables, women with secondary infertility had a higher likelihood of having fallopian tube obstruction on hysterosalpingography than did those with primary infertility. Our study supports continued routine evaluation for tubal patency in patients with secondary infertility. Among parous women, there is no evidence that cesarean delivery places patients at increased risk of abnormal hysterosalpingograms.

HOXA10 mutations in congenital absence of uterus and vagina.

OBJECTIVE: To analyze the HOXA10 genes in CAUV patients for mutations. Congenital absence of the uterus and vagina (CAUV) is the most extreme female reproductive tract developmental defect known. The HOXA10 gene is expressed in the developing and adult uterus. Female mice with loss-of-function Hoxa10 gene mutations have anteriorly directed homeotic transformations of the uterus. Because the HOXA10 gene is expressed in the embryonic paramesonephric (Müllerian) ducts, abnormally low expression by mutant HOXA10 genes might cause CAUV. This hypothesis was tested by analyzing the HOXA10 genes in CAUV patients for mutations. DESIGN: Case-control study. SETTING: Academic reproductive endocrinology and infertility practice. PATIENT(S): Blood samples were obtained from 26 patients with CAUV and 30 normal controls. INTERVENTION(S): DNA samples prepared from blood leukocytes were used as templates for polymerase chain reaction (PCR) amplification of DNA fragments from the HOXA10 gene. The gene fragments were tested for DNA sequence differences using denaturing gradient gel electrophoresis (DGGE). MAIN OUTCOME MEASURE(S): To detect DNA sequence differences between patients with CAUV and normal controls. RESULT(S): No DNA sequence differences were found in either patients with CAUV or normal controls in either of the two protein-coding exons of the HOXA10 gene. CONCLUSION(S): Because no HOXA10 gene mutations were found in 26 patients from 25 unrelated families, germ- line mutations in the HOXA10 gene are not a common cause of CAUV.

Direct regulation of HOXA10 by 1,25-(OH)2D3 in human myelomonocytic cells and human endometrial stromal cells.

Vitamin D receptor (VDR) and the functionally active form of its ligand, 1,25-(OH)2D3, have been implicated in female reproduction function and myeloid leukemic cell differentiation. HOXA10 is necessary for embryo implantation and fertility, as well as hematopoeitic development. In this study, we identified a direct role of vitamin D in the regulation of HOXA10 in primary human endometrial stromal cells, the human endometrial stromal cell line (HESC), and in the human myelomonocytic cell line, U937. Treatment of primary endometrial stromal cells, or the cell lines HESC and U937 with 1,25-(OH)2D3 increased HOXA10 mRNA and protein expression. VDR mRNA and protein were detected in primary uterine stromal cells as well as HESC and U937 cells. We cloned the HOXA10 upstream regulatory sequence and two putative vitamin D response elements (VDRE) into luciferase reporter constructs and transfected primary stromal cells and HESC. One putative VDRE (P1: -385 to -434 bp upstream of HOXA10) drove reporter gene expression in response to treatment with 1,25-(OH)2D3. In EMSA, VDR demonstrated binding to the HOXA10 VDRE in the presence of 1,25-(OH)2D3. 1,25-(OH)2D3 up-regulates HOXA10 expression by binding VDR and interacting with a VDRE in the HOXA10 regulatory region. Direct regulation of HOXA10 by vitamin D has implications for fertility and myeloid differentiation.

Variations in individual physician success rates within an in vitro fertilization program might be due to patient demographics.

OBJECTIVE: To determine whether there are variations in individual physician success rates in an IVF program, even with uniform laboratory and treatment protocols. DESIGN: Retrospective analysis. SETTING: Boston IVF, a private practice. PATIENT(S): Patients <38 and 38-40 years of age who underwent non-donor egg, fresh embryo transfer (ET). INTERVENTION(S): Retrospective analysis of IVF success rates for Boston IVF for the year 1999, as reported to the Society of Assisted Reproductive Technology. MAIN OUTCOME MEASURE(S): Each individual physician's clinical pregnancy and live birth rates for patients aged <38 and 38-40 years for the year 1999. Pregnancy rates were also obtained for an "ideal patient group." RESULT(S): Among 13 physicians, the clinical pregnancy rate in the <38-year age group ranged from 20.5% to 35.1% and the live birth rates from 17.8% to 31.1%. For the 38-40-year age group, the clinical pregnancy rate ranged from 10.6% to 29.8% and live birth rates from 7.0% to 25.5%. There was no statistical difference in the clinical pregnancy rate for the ideal patient group. CONCLUSION(S): In the ideal patient group, in which patient demographics are uniform, there are no statistical differences in individual physician performance within the same IVF program. Variation exists in the success rates between the physicians in the <38- and 38-40-year age groups. Possibly this is owing to patient demographics.

Risk of death in pregnancy achieved through oocyte donation in patients with Turner syndrome: a national survey.

UNLABELLED: To determine the risk of death in pregnant women with Turner syndrome who were treated with oocyte donation, and to ascertain the prevalence of preconception cardiac screening in these patients. DESIGN: Survey and literature review. SETTING: Academic infertility center. PARTICIPANT(S): All 258 donor-egg programs in the 1997 Assisted Reproductive Technology Success Rates publication from the Society for Artificial Reproductive Technology were surveyed by fax or telephone. MAIN OUTCOME MEASURE(S): Death in pregnancy conceived through oocyte donation and proportion of patients prescreened with echocardiography. RESULTS: One hundred thirty-four (52%) programs reported 146 Turner patients treated, resulting in 101 pregnancies. One patient died from aortic rupture while awaiting treatment; 72 (49.3%) patients were pre- screened with echocardiography. No deaths in pregnancy were reported. A literature review identified four case reports of Turner patients who died during pregnancy in the United States during the same time period. CONCLUSION(S): The maternal risk of death from rupture or dissection of the aorta in pregnancy may be 2% or higher. Patients with Turner syndrome have not been adequately screened with echocardiography before treatment. Specialists who treat patients with Turner syndrome need to be aware of their cardiac risk and its potential exacerbation from the increased cardiac demands of pregnancy.

Normal onset of puberty have definitions of onset changed?

Puberty is the sequence of events that culminates in the ability to procreate. It is widely accepted that the onset of puberty in girls occurs on average at 8 years of age and that onset prior to 8 years of age is precocious puberty. As a result of the cross-sectional study by the American Association of Pediatrics, a movement exists to change the age limit of the onset of puberty to 6 years of age in black girls and 7 years of age in white girls. We should be cautious in adhering to strict age limits when diagnosing precocious puberty. Also the rapidity and progression of puberty should be evaluated, and if appropriate, therapy to suppress pubertal development considered.