Hormonal manipulation of endometrial maturation

Three experimental protocols were devised to induce endometrial maturation in 12 women with ovarian failure. Each was planned to serve a dual purpose: to resolve a particular clinical situation related to synchronization between ovum donor and recipient and to answer a specific question about endometrial physiology. A fourth protocol of sequential estrace (2-6 mg/day) and progesterone (P4; 25-50 mg/day, im) simulating the 28-day natural cycle, served as a control protocol (18 cycles). A short follicular phase protocol consisted of only 6 days of estrogen (E) administration before addition of P4 (13 cycles). In the long follicular phase protocol (5 cycles), estrace was given for 3-5 weeks, and P4 administration was accordingly postponed. In 6 accelerated secretory transformation cycles, 150 mg/day P4 were administered, im, from day 15 onward. The adequacy of the induced endometrial cycles was evaluated by hormonal, morphological, and histochemical criteria relevant to endometrial normalcy and receptivity. Serum estradiol levels and the areas under the estradiol curves for the long and short follicular phase protocols differed significantly from those during the control cycles (P less than 0.005). Areas under the estradiol curves in the accelerated secretory transformation protocol yielded significantly higher P4 values than those in all other protocols (P less than 0.05). All biopsies in the 3 experimental protocols compared favorably with those of the control protocol. Glycocalyx intensity (periodic acid-Schiff) and the amount of galactose residues in the glycocalyx (Ricinus communis-I agglutinin) were greatest during the periimplantation interval. We conclude that a very short exposure of the human endometrium to E or, conversely, prolonged E stimulation will allow normal endometrial maturation with the addition of P4. Supraphysiological doses of P4 in the accelerated secretory transformation protocol significantly enhanced endometrial maturational processes.     

Comprehensive profiling of circulating microRNA via small RNA sequencing of cDNA libraries reveals biomarker potential and limitations

We profiled microRNAs (miRNAs) in cell-free serum and plasma samples from human volunteers using deep sequencing of barcoded small RNA cDNA libraries. By introducing calibrator synthetic oligonucleotides during library preparation, we were able to calculate the total as well as specific concentrations of circulating miRNA. Studying trios of samples from newborn babies and their parents we detected placental-specific miRNA in both maternal and newborn circulations and quantitated the relative contribution of placental miRNAs to the circulating pool of miRNAs. Furthermore, sequence variation in the placental miRNA profiles could be traced to the specific placenta of origin. These deep sequencing profiles, which may serve as a model for tumor or disease detection, allow us to define the repertoire of miRNA abundance in the circulation and potential uses as biomarkers.     

Wedge metroplasty for the septate uterus: an update

Twenty-one patients with septate uteri and 2 patients with a T-shaped uterine anomaly and recurrent abortions underwent wedge metroplasty during the period from September 1978 to August 1983. Thirteen patients had a characteristic history of one or more abortions associated with the septate uterus and absence of other metabolic and endocrine abnormalities. Ten other patients, including the two with a T-shaped uterine anomaly, either had one or more abortions of an uncharacteristic nature with absence of other abnormalities or had one or more characteristic abortions in addition to the presence of other metabolic, endocrine, or surgically correctable disease. The application of wedge metroplasty for the surgical reconstruction of the uterus yielded equally gratifying results in both groups with approximately two thirds of the patients having a term delivery or carrying a pregnancy in the third trimester.     

Effect of parental age on fertilization and pregnancy characteristics in couples treated by intracytoplasmic sperm injection

The purpose of this study was to investigate any influence of maternal and/or paternal age on gamete characteristics and pregnancy outcomes in intracytoplasmic sperm injection (ICSI) cycles. In all, 821 consecutive ICSI cases were analysed retrospectively. While a significant linear decline in semen volume was detected, no significant differences in the concentration, motility or morphology of the spermatozoa were found with paternal ageing. A significant decline in the number of oocytes retrieved and the number of mature oocytes obtained was found with advancing maternal age. An increase in the occurrence of digyny was noted with parental ageing, while no difference in single or bipronuclear fertilization was found. Older women had a decreased incidence of single pronucleus formation and an increase in digyny, but no significant difference in the percentage of oocytes that underwent two-pronuclear fertilization was detected with regard to maternal ageing. Pregnancy outcomes were not influenced by the age of the male partner, while a strong negative correlation was found with maternal ageing. To better analyse male partner ageing as a factor affecting pregnancy outcome, we analysed a subgroup of patients with a female partner aged <35 years who underwent ICSI. No paternal influence on ICSI pregnancy outcome was found in this subgroup of patients. We conclude that the influence on pregnancy outcome after ICSI is related mostly to maternal and not paternal age.      

Spontaneous and pharmacologically induced remissions in patients with premature ovarian failure

To determine the fertility potential of patients with apparent ovarian failure, a retrospective analysis of 86 ovarian failure patients in the Norfolk oocyte donation program was performed. None of the 23 patients with primary ovarian failure ovulated. Seven of 63 (11.1%) with secondary ovarian failure did ovulate, and three of 63 (4.8%) conceived and delivered normal, healthy infants. Of patients whose etiology for ovarian failure was partial ovarian resection or chemotherapy, the ovulation rate and pregnancy rate were 30.8 and 15.4%, respectively, compared with 5.0 and 1.7%, respectively, for the other patients with secondary ovarian failure. Serum estradiol and FSH obtained during hormone replacement were not predictive of the resumption of normal reproductive functions. Therefore, it is recommended that patients with secondary ovarian failure, especially in the better-prognosis group, be treated with a trial of estradiol replacement and have close monitoring for ovulation before oocyte donation.     

Ureaplasma urealyticum andMycoplasma hominis detected by the polymerase chain reaction in the cervices of women undergoingin vitro fertilization: Prevalence and consequences

Purpose The prevalence of Ureaplasma urealyticumand Mycoplasma hominisin the endocervix at the time of oocyte collection in women undergoing in vitrofertilization (IVF) was examined using the polymerase chain reaction (PCR).Methods All women were treated with tetracycline following sample collection.Results U. urealyticumwas identified in 56 (17.2%) of 326 women while M. hominiswas present in only 5 (2.1%) of 235 women. U. urealyticumwas detected at a higher frequency (P =0.01) in those women whose IVF cycle failed prior to embryo transfer. This organism was present in 8 of 19 (42.1%) women with either no fertilization or no embryo transfer, 19 of 148 (12.8%) who had no evidence of pregnancy following embryo transfer, 6 of 30 (20,0%) who had only a transient (biochemical) pregnancy, 5 of 14 (35.7%) with a spontaneous abortion, and 18 of 115 (15.6%) with a term birth. Of the eight women with U. urealyticumwho had no embryos transferred, male factor was the cause of infertility in five cases, two women had tubal occlusions while in one woman the diagnosis was idiopathic. Therefore, poor sperm quality, and not a U. urealyticuminfection, might explain the failure of most of these cases to proceed to the stage of embryo transfer. Analysis of all patients revealed no association between male factor infertility and U. urealyticumin the cervix.Conclusions U. urealyticum,but not M. hominis,is present in the cervices of many culture-negative women. Its presence, however, does not influence IVF outcome subsequent to embryo transfer in women treated with tetracycline after oocyte retrieval.Presented at the IXth World Congress on In Vitro Fertilization and Alternate Assisted Reproduction, April 3–7, 1995, Vienna, Austria.     

The role of in vitro fertilization in infertile patients with endometriosis

Thirty-nine cycles were studied in patients with a history of endometriosis who went through in vitro fertilization. In 15 cycles, there was no evidence of endometriosis; in 10 cycles, the patients had mild or moderate disease; in 14 cycles, severe or extensive endometriosis was found. The pregnancy rates per cycle were 33%, 60%, and 7%, respectively (groups I and II, no significant difference; groups II and III, P less than 0.01). The difference was due to the different number of oocytes aspirated at laparoscopy because of technical problems in the cases with severe and extensive disease. There was also a significant difference in the number of pregnancies per transferred cycles. There was no difference in the luteal phase in the three groups. The reproductive potential, which seemed to be similar in groups I and II, was severely impaired in the group with severe endometriosis.     

Effects of the severity of tubo-ovarian disease and previous tubal surgery on the results of in vitro fertilization and embryo transfer

The purpose of this study was to evaluate the ovarian response and in vitro fertilization/embryo transfer (IVF-ET) results in patients with tubal infertility and two ovaries, according to (1) the degree and extent of pelvic disease (isolated tubal or tubo-ovarian) and (2) previous adnexal surgical procedures. A total of 549 patients who underwent 1031 IVF-ET cycles were evaluated. Significant findings were as follows: (1) No differences were found in the number of preovulatory oocytes, fertilization rates, or serum estradiol levels in the follicular phase between any classes of tubo-ovarian disease. (2) Patients with a "frozen pelvis" had significantly fewer follicles aspirated than those in any other category, although they had equivalent numbers of preovulatory oocytes retrieved and pregnancy rates. (3) Patients with previous bilateral tubal ligation had higher pregnancy rates than patients with severe tubo-ovarian disease. (4) The type of prior pelvic surgical procedure had no effect on IVF-ET outcome. Although patients with no cause of infertility other than tubal ligation had better results, these patients had previously proven fertility. We conclude that neither the stage of tubo-ovarian disease nor any history of pelvic adhesions or tubal surgery has a significant impact on the efficiency of IVF-ET.     

Taking a basal follicle-stimulating hormone history is essential before initiating in vitro fertilization

OBJECTIVE: To analyze IVF outcomes in patients with a history of one or more elevations in basal FSH who have a normal basal FSH at the start of their IVF cycle, compared with the general IVF population. DESIGN: Retrospective clinical study. SETTING: University hospital. PATIENT(S): General IVF patient population. INTERVENTION(S): Patients received standard IVF gonadotropin protocols, oocyte retrieval, and embryo transfer. MAIN OUTCOME MEASURE(S): Oocyte yield, fertilization, implantation, clinical pregnancy, and cancellation rate. RESULT(S): Oocyte yields were lower in patients with a history of elevated basal FSH, for all age groups, and showed an age-dependent decline in all patients. Over the age of 40 years, both implantation and clinical pregnancy rates were lower in these patients, with no significant difference observed in patients under the age of 40 years. No pregnancies were observed in patients with a history of three or more elevated FSH levels, regardless of age. CONCLUSION(S): A history of elevated basal FSH levels in patients under the age of 40 years predicts a lower oocyte yield in IVF cycles with normal basal FSH levels but does not translate to either lower pregnancy or implantation rates. Patients aged >40 years with prior elevations in basal FSH levels have both compromised ovarian response and compromised embryo quality relative to those with normal FSH levels, as illustrated by lower oocyte yield, higher cancellation rates, and lower implantation and pregnancy rates.