Methods used to improve gamete efficiency.

Male factor infertility accounts for a significant percentage of problems in infertile couples. With clinical utilization of the technologies for selection of good-quality spermatozoa from the ejaculate, our ability to successfully treat the severely affected male factor couple has improved. However, it must be remembered that even with current technologies, fertilization success is reduced in these patients but remains above a 50% level. Other factors that can be used in the future to improve on these statistics are being investigated in regard to the in vitro environment for gametes, that is, the type of culture medium, the methods of coincubation of the sperm and egg, and other methods of enhancement of sperm fertilizing potential. However, methods of sperm preparation will achieve improvement in a percentage of these males treated, and can be used to improve fertilization and pregnancy success. It is important to understand the limitations of the zona-free hamster test, but it is also important to use that test as a screening method for sperm handling. By utilizing the SPA to select out the optimal method of sperm preparation, the fertilization and pregnancy outcome can be improved. Overall, the live-birth rate in male factor infertile couples is lower than non-male-factor couples treated by IVF and GIFT. Until more is known about basic spermatozoal function, and the ability to improve that function in affected males, the live-birth rate should not be expected to change substantially.

Genital tract reconstruction in a patient with congenital absence of the vagina and hypoplasia of the cervix.

A 15-year-old female presented with congenital absence of the vagina and a blind ending hypoplastic cervix. The uterine cavity appeared normal by ultrasound examination, and the patient experienced molimina. Cognizant of risks and failures of described attempts at correction, reconstruction was performed using a series of stents covered with skin grafts. At 21 months postoperatively, the patient now has a functioning vagina and menstruates regularly. The desire to avoid a hysterectomy coupled with new alternatives in the management of the infertile patient resulted in the approach described.

Effect of vaginal bleeding in early pregnancy on outcome.

The effect of vaginal bleeding in the first half of pregnancy on fetal outcome is retrospectively analyzed in 523 cases and compared with a control group of 6706. Early-pregnancy bleeding was found to be associated with more preterm deliveries and lower birth weight. The frequency of congenital anomalies and growth-retarded infants was unaffected. Neonatal death and low Apgar scores were seen more often than expected, but stillbirth rates were not significantly increased. These data suggest that vaginal bleeding in early pregnancy is a useful indicator of risk for suboptimal outcome.

Sonographic uterine predictors of pregnancy in women undergoing ovulation induction for assisted reproductive treatments.

OBJECTIVE: To determine preovulatory uterine sonographic predictors of pregnancy in women undergoing ovulation induction for assisted reproductive treatments. DESIGN: Prospective evaluation of uterine sonographic and vascular flow profiles in women stimulated with leuprolide acetate and hMG. SETTING: Private fertility center and tertiary-care academic center. PATIENTS: Ninety-six women underwent 102 cycles of ovulation induction for IVF (46), GIFT (20), and zygote intrafallopian transfer (36). MAIN OUTCOME MEASURES: Endometrial texture, thickness, resistance index at the first branch of uterine artery, diastolic blood flow, and pregnancy outcome (no conception, spontaneous abortion, and delivery). RESULTS: Triple-lined pattern was predominant in women who delivered liveborn infants (P < 0.005). Endometrial pattern and diastolic blood flow were the only predictive markers of term pregnancy (P < 0.001 and P < 0.05, respectively). CONCLUSION: Preovulatory triple-lined sonographic endometrial texture and the presence of end diastole blood velocities at the first branch of uterine artery are the most important uterine predictors of conception.

Occurrence of a spontaneous luteinizing hormone surge in superovulated cycles--predictive value of serum progesterone.

A preovulatory increase in serum progesterone (P) precedes the occurrence of an endogenous luteinizing hormone (LH) surge in a majority of women. This study evaluates whether a single daily measurement of serum P could reliably identify a spontaneous LH surge in women undergoing controlled ovarian hyperstimulation. Eighty-four infertile women received either clomiphene citrate and human menopausal gonadotropin (hMG), or hMG alone. Serum P levels were increased significantly the morning of the day of an endogenous LH surge (P less than 0.01). A 2-fold rise in the serum P levels was associated with a predictability of 64.4% of a LH surge; however, a 4-fold increase in serum P could accurately predict a spontaneous endogenous LH discharge in 93.3% (P less than 0.001) of cases.

An alternate approach to controlled ovarian hyperstimulation in "poor responders": pretreatment with a gonadotropin-releasing hormone analog.

Pharmacologic hypophysectomy was induced with a subcutaneous injection of leuprolide acetate before the administration of exogenous gonadotropins for multiple follicle development in 27 women who had previously responded poorly to conventional controlled ovarian hyperstimulation (COH). Pituitary desensitization occurred within 6 days and concurrent COH with exogenous gonadotropins resulted in an enhanced yield of oocytes in comparison to previous COH attempts (P less than 0.05). Fertilization and pregnancy rates also were higher with gonadotropin-releasing hormone agonist (GnRHa) treatment (P less than 0.01). The administration of leuprolide acetate effectively suppressed endogenous gonadotropin secretion when initiated in the follicular or luteal phase of the menstrual cycle. GnRHa therapy can appreciably facilitate the management of gonadotropin therapy, and increase the probability of oocyte collection and pregnancy.

Enhanced penetration of zona-free hamster ova by sperm prepared by Nycodenz and Percoll gradient centrifugation.

The effect of sperm penetration capacity after selection procedures using Percoll (Pharmacia AB, Uppsala, Sweden) and Nycodenz (Nycomed Diagnostics, Oslo, Norway) gradient centrifugation was compared with double-washed and swim-up in 47 subfertile men. The results of sperm motility, velocity, and amplitude lateral head displacement showed no significant improvement with the centrifugation procedures. The sperm penetration assay results obtained with double-washed and swim-up technique were poor (2.7% +/- 1.7%), however, a significant enhancement was obtained by Percoll (16.3% +/- 3.7%) and Nycodenz (15.8% +/- 3.3%) processing. Nycodenz centrifugation allowed sperm penetration of zona-free hamster ova at comparable rates to Percoll separation.

Peritoneal fluid plasminogen activator activity in endometriosis and pelvic adhesive disease.

Plasminogen activator activity in PF was assayed by the fibrinolysis method described by Strickland and Beers. In 45 patients studied, there were no discernible differences according to whether patients had endometriosis and/or pelvic adhesive disease. No differences were detected according to when in the menstrual cycle the sample of PF was obtained. These data are in concordance with a previous report and taken together suggest that there is no difference in fibrinolytic mechanisms in PF in patients with or without endometriosis and/or pelvic adhesive disease, when compared with control subjects. If such differences exist, they may be present in the tissues, per se, but are not discernible in PF.

Interrelationships between plasma hormone levels and the content of total protein, gonadotropins and steroid hormones in antral fluids of women undergoing in vitro fertilization.

Follicle development was induced in 41 women with follicle-stimulating hormone (FSH) and human menopausal gonadotropin. Blood samples were drawn and follicular fluids (FF) were aspirated when two or more follicles attained diameters of 15 to 17 mm. Levels of estradiol (E2), progesterone (P), FSH, and luteinizing hormone (LH) were determined in samples by radioimmunoassay, and relationships between the measured parameters in antral fluids and in serum were examined by least-squares linear regression analysis. Levels of LH in serum correlated with LH and FSH levels in FF (P less than 0.005). Concentrations of FSH in serum were positively related to levels of LH, FSH, E2, and total protein in FF (P less than 0.005). E2 levels in serum were predictive of E2 levels in FF only, and levels of P in serum were directly correlated with P levels in FF (P less than 0.05). With respect to the peculiarly broad range of predictions that could be drawn from the FSH content of serum, peripheral FSH provided a better predictive index of the chemical composition of antral fluid than did the level of any other single hormone measured in serum.

Levels of steroid and protein hormones in antral fluids of women treated with different combinations of gonadotropins, clomiphene citrate, and a gonadotropin-releasing hormone analog.

Levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone (P), and total protein in follicular fluids collected from 18 patients pretreated with a gonadotropin-releasing hormone analog (GnRHa), in association with human menopausal gonadotropin (hMG) and FSH, were compared with values for 69 patients treated with FSH, hMG, FSH/hMG, or clomiphene citrate (CC)/hMG in an in vitro fertilization (IVF) program. The authors have established a number of significant differences in chemical and physical properties of follicular fluids of patients treated by different regimen, and concur with earlier evidence that the volume of a follicle, and its P and total protein content, are related to the maturity of the oocyte nested within the follicle. Overall, however, differences in concentrations of gonadotropins in follicular fluids between groups were not consistent with differences in follicular fluid steroid levels, and levels of immunoactive gonadotropins in follicular fluids were not in accord with dosages of exogenous immunoactive gonadotropin administered during hyperstimulation. The most favorable outcomes of IVF (greater than 70% of oocytes fertilized) were established with oocytes collected from patients treated with FSH only or with CC/hMG, and patients treated with FSH only yielded the highest average number of oocytes which fertilized in vitro (6.2 per patient).

XY sperm separation for sex selection.

At present, laboratory methods that can successfully differentiate X- from Y-bearing sperm do exist; namely, staining with quinacrine mustard and DNA flow cytometry. However, methods that can successfully and reproducibly separate X- from Y-bearing sperm with resultant functionally intact sperm have yet to be developed. The area of sex selection is under intensive investigation, and a reliable method of separation will undoubtedly become available in the near future. To the extent that these techniques would be used to help couples avoid sex-linked genetic diseases, preimplantation gender selection is ethically justifiable. Social and ethical factors are important considerations in justifying other applications of these techniques.

Diagnosis of female infertility. A comprehensive approach.

The evaluation of the infertile woman involves a careful history, physical examination and laboratory tests. A thorough and systematic investigation is of paramount importance to establish the diagnosis and generate a treatment plan.

Influence of early ICSI-derived embryo sHLA-G expression on pregnancy and implantation rates: a prospective study.

BACKGROUND: We have previously reported the retrospective observation that when at least one embryo, transferred on day 3, expressed sHLA-G above the geometric mean (sHLA-G+) 46 h post-ICSI, there was a marked improvement in both pregnancy (PR) and implantation (IR) rates. METHODS: The media surrounding individual embryos derived from ICSI performed on oocytes from 482 women < or =43 years of age were tested for sHLA-G expression by specific ELISA. RESULTS: We report here prospective results showing improved IVF results following the transfer of 'good quality' embryos (7-9 cells with <20% fragmentation) by preferentially including at least one sHLA-G+ embryos. PR and IR for women < or =38 years were 63% and 32% when one transferred embryo was sHLA-G+, and 69% and 36% when at least two embryos were sHLA-G+. When none of the embryos transferred was sHLA-G+, PR and IR were 25% and 13%, respectively. Comparable PR and IR for women 39-43 years were 29% and 11% when none of the transferred embryos were sHLA-G+; 38% and 15% when at least one sHLA-G+ embryo was transferred; and 61% and 26% when at least two 2 sHLA-G+ embryos were transferred. The data were stratified by patient age. CONCLUSIONS: PR and IR increased with the addition of each sHLA-G+ embryo, regardless of age. While there are significant barriers to routine embryo sHLA-G testing, we believe that if implemented, this would provide a mechanism for optimizing IVF PR while minimizing the risk of multiple pregnancies.

Transvaginal color Doppler ultrasonography in reproductive gynecology.

Transvaginal color Doppler sonography (TVSCD) is one of the most important recent developments in gynecology. TVSCD provides relevant information on uterine and ovarian blood flow and aids in the identification of pregnancy viability as well as the early diagnosis of ectopic pregnancy. TVSCD also facilitates differential diagnosis of benign and malignant pelvic pathology.

Resection of large uterine septum during early pregnancy and at the oocyte retrieval--peculiarities of two cases.

Two cases of hysteroscopic metroplasties for large septate, one performed at the time of oocyte retrieval, and the second at the time of curettage for early first trimester spontaneous pregnancy loss, are reported. The peculiarities of medical circumstances and surgical approaches are discussed. Each patient had an excellent post-surgical result and a successful pregnancy. The notion that the performance of hysteroscopic surgery in women presenting with supraphysiological serum oestradiol concentrations or an early miscarriage would increase intra-operative bleeding and post-operative complications respectively is challenged by this report. The authors emphasize that thorough counselling, meticulous planning, appropriate follicular phase timing and excellent surgical techniques remain the mainstay for success.

Selective salpingography with an insemination catheter in the treatment of women with cornual fallopian tube obstruction.

The effectiveness of selective tubal cannulation using a simple and inexpensive tubal insemination catheter was evaluated in 23 infertile patients with cornual obstruction demonstrated by hysterosalpingography. Selective fluoroscopic tubal catheterization was accomplished in 95% of the patients with resulting tubal patency in 70% of the procedures (28 recanalizations out of 40 Fallopian tubes). Eight patients (34.8%, eight out of 23) became pregnant, six went on to full-term deliveries and two experienced spontaneous first-trimester abortions. One women conceived twice, and delivered a singleton pregnancy after the first recanalization and a twin gestation after the second salpingography. No complications were reported. The results of this study emphasize the ease, cost effectiveness and safety of this method, encouraging its use in patients with cornual Fallopian tube obstruction either as the sole therapeutic approach or in association with other assisted conception treatment alternatives.

Preovulatory sonographic uterine receptivity index (SURI): usefulness as an indicator of pregnancy in women undergoing assisted reproductive treatments.

To evaluate the uterine component as a determinant variable in the probability of establishing a pregnancy after assisted reproductive treatments, we introduced a mathematical formula derived from standard endovaginal uterine monitored color Doppler imaging parameters. We analyzed 102 cycles of ovarian stimulation with leuprolide acetate and exogenous gonadotropins resulting in 52 clinical pregnancies by stepwise logistic regression analysis. Sonographic endometrial pattern, thickness, diastolic blood flow, and resistive index variables were transformed into categorical variables and forced to yield a regression equation. Sonographic uterine receptivity index was calculated as a summation of four times endometrial pattern, five times resistive index, and two times diastolic blood flow. This index yielded values for each patient in a range of 0 to 15. Scores > or = 13 were associated with a successful outcome in 79.4% of the patients, whereas scores between 8 and 12 were accompanied by 45.8% pregnancy rates (P = 0.01), and scores < or = 7 had successful treatment outcome in only 7.7% (P = 0.0001). The scores obtained by this mathematical equation provide the ability to make reliable predictions about the outcome of assisted reproductive treatments in women undergoing ovulation induction with leuprolide acetate and human menopausal gonadotropins.

Perinatal outcome after in-vitro fertilization-surrogacy.

The perinatal outcome of pregnancies (both single and multiple) established after in-vitro fertilization (IVF)-surrogacy was evaluated and compared to the outcome of pregnancies that resulted from standard IVF. Analysis of medical records and a telephone interview with physicians, IVF-surrogates, and commissioning mothers were conducted to assess prenatal follow up and delivery care in several hospitals. 95 IVF-surrogates delivered 128 liveborn (65 singletons, 27 sets of twins and two sets of triplets). The commissioning mothers and the IVF-surrogates average ages were 37.7 +/- 5.0 and 30.4 +/- 4.7 years old respectively. IVF-surrogates carrying twin and triplet gestations delivered substantially earlier than those who gestated singleton pregnancies (36.2 +/- 0.4 versus 35.5 versus 38.7 +/- 0.3 weeks gestation respectively; P < 0.001). Twin newborns were significantly lighter than singleton infants born through IVF-surrogacy (2.7 +/- 0.06 versus 3.5 +/- 0.07 kg; P < 0.001). The incidence of low birth weight infants rose from 3.3% in the single births to 29.6% (P < 0.01) in the twins and to 33.3% in the triplets born through IVF-surrogacy. The incidence of prematurity was significantly greater in both twins delivered by IVF-surrogates (20.4%) and infertile IVF patients (58%). The occurrence of pregnancy-induced hypertension and bleeding in the third trimester was four to five times lower in the IVF-surrogates, independently of whether they were carrying multiples. The incidence of Caesarean section was 21.3% for singleton gestations, while two times higher in the IVF-surrogates carrying multiples (56.3%). Postpartum complications occurred in 6.3% of patients and the incidence of malformation was similar to those reported for the general population. The results provide general reassurance regarding perinatal outcome to couples who wish to pursue IVF-surrogacy.