Sander S. Shapiro

Plasma estradiol is superior to ultrasound and urinary estriol glucuronide as a predictor of ovarian hyperstimulation during induction of ovulation with menotropins

In order to compare the effectiveness of 8:00 A.M. plasma 17 beta-estradiol (E2), 24-hour urinary estriol glucuronide (E3G), and ultrasound as predictors of ovarian hyperstimulation, 70 cycles of induction of ovulation with 5:00 P.M. to 8:00 P.M. injection of menotropins from 28 subjects were evaluated. Hyperstimulation was four times more frequent in pregnancy than in nonpregnancy cycles (P less than 0.005). The hyperstimulation score (range, 0 to 6) was correlated with plasma E2 (0.63, P less than 0.01), the number of follicles (0.31, P less than 0.05), the duration of treatment (0.31, P less than 0.05), and urinary E3G (0.25, P less than 0.05). Plasma E2 was the best predictor of the hyperstimulation score, and plasma E2 was far superior to both urinary E3G and the number of follicles. Management with ultrasound alone is insufficient to prevent severe ovarian hyperstimulation. With this protocol, human chorionic gonadotropin may be given as soon as the first follicle reaches 1.4 cm in diameter as long as plasma E2 is less than 4000 pg/ml. The values of plasma E2 are dependent on the interval between blood sampling and injection of menotropins.

Artificial donor insemination: fresh versus frozen semen; the patient as her own control

The efficacies of fresh versus cryopreserved semen in the treatment of male factor infertility by artificial insemination by donor (AID) semen were directly compared by using the patient as her own control. In any one cycle, either fresh or frozen semen was used. The type of semen preparation was randomly assigned for the first cycle and varied thereafter according to donor availability. The same donor was used for a given patient in six consecutive cycles. We treated 381 patients in this way. In 676 cycles fresh semen was used and 128 pregnancies were achieved. Fecundability, the chance of getting pregnant per cycle of exposure, was 18.9% with fresh semen. In 1200 cycles cryopreserved semen was used and 60 pregnancies occurred, for a fecundability of 5.0%. Therefore, in our clinic, fresh semen is more than three times as likely to induce pregnancy as frozen semen. The design that has been used in this therapeutic protocol provides a technique for internal quality control of the cryopreservation process and for the investigation of other variables potentially affecting the success rates with AID.

Improved cryopreserved semen fecundability in an alternating fresh-frozen artificial insemination program

This study with glycerol and increased number of motile sperm inseminated showed an increase in f to 10.4% for frozen semen and 27.4% for fresh semen. There is a significant (P less than 0.01) difference in pregnancy rate when greater than 100 million motile sperm are inseminated (31.3%) than when less than that number are inseminated (11.9%) in the first cycle when frozen semen is used.

Hysterosalpingography with oil contrast medium enhances fertility in patients with infertility of unknown etiology

Previous studies have suggested increased fertility rates following hysterosalpingography (HSG) using oil as compared with aqueous contrast medium. To compare the possible fertility-enhancing effects of two agents used for HSG, this prospective randomized study evaluated the subsequent fertility rates in 121 patients who underwent HSG, in which either oil or aqueous contrast medium was used. After random assignment to either agent, patients were observed for four menstrual cycles after HSG without resorting to any therapy other than clomiphene citrate where indicated. The pregnancy rates for the four cycles after HSG were compared with chi-square analysis in the total study and in the diagnostic subgroups. The subgroup with infertility of unknown cause had a significantly higher pregnancy rate after HSG with oil than after HSG with aqueous contrast medium. No significant difference was seen for any other subgroup or for the overall cohort.

Transfer of nonassisted hatched and hatching human blastocysts after in vitro fertilization

OBJECTIVE To determine the feasibility of performing blastocyst transfer 6 days after oocyte insemination. DESIGN Retrospective clinical study. SETTING University-based IVF center. PATIENT(S) All cases of IVF over a 1-year span of time (June 1998-1999) in which seven 2PN embryos were available for transfer. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Implantation, pregnancy, and multiple pregnancy rates. RESULT(S) Transfer of blastocysts on days 5 and 6 resulted in implantation rates of 69% and 33% (P=0.0006), clinical pregnancy rates of 89% and 59% (P=0.05), and multiple pregnancy rates of 39% and 10% (P=0.03), respectively. In cases in which blastocysts were spontaneously hatching or hatched on day 6 (9% of embryos), implantation and pregnancy rates were 52% and 80%, respectively. Embryos were successfully frozen in the hatched or hatching state with resultant clinical pregnancies. CONCLUSION(S) Transfer of embryos can be delayed to day 6 after oocyte insemination at which time a small percentage of embryos will hatch. Hatching of embryos by day 6 is a favorable prognostic factor for IVF outcome. Embryos that fail to hatch by day 6 may have a lower implantation potential. Difficulty with hatching embryos sticking to the transfer catheter was not encountered. Furthermore, hatching and hatched embryos can be frozen and with subsequent transfer result in pregnancies.

Quality control in the in vitro fertilization laboratory.

Abstract Viability of gametes and embryos is explored as it relates to in vitro fertilization (IVF) and embryo culture (EC): exposure to cytotoxic materials, water quality, gas composition, temperature, hydrogen ion concentration and osmolality of media, and light exposure. The use of various assay techniques to strengthen quality control procedures in the IVF/EC laboratory is evaluated. In addition, original data concerning embryo toxicity of plasticware, changes in osmolality of culture medium over time, potential hazards of cleaning and sterilizing reusable labware and comparisons of 1-cell versus 2-cell embryo assays are discussed. Suggestions are then made concerning techniques to improve quality control in the IVF/EC laboratory.

Ultrasound evaluation of estrogen monitoring for induction of ovulation with menotropins

Twenty-five cycles of induced ovulation with menotropins were investigated blindly with ultrasound to evaluate estrogen monitoring. Plasma 17 beta-estradiol (E2) and urinary estriol glucuronide (E3G) correlated with total ovarian volume (0.58, 0.58), total follicular volume (0.56, 0.52), volume of the largest follicle (0.53, 0.54), and days of administration of menotropins (0.49, 0.44), respectively. The mutual correlations of days of menotropin administration, volume of the largest follicle, E2, and E3G with total follicular volume explained the correlations of E2 and E3G with days of administration of menotropins and with volume of the largest follicle. Thus, multiple small follicles can reproduce the E2 or E3G levels associated with a single mature follicle if they result in the same total follicular volume. As menotropins were administered for progressively longer periods, the number of maturing follicles increased. We conclude that ultrasound appears to be useful for monitoring induction of ovulation with menotropins since it provides more accurate information on follicular number and size than can be obtained by estrogen determinations alone.

Differences in serum follicle-stimulating hormone uptake after intramuscular and subcutaneous human menopausal gonadotropin injection

OBJECTIVE To determine the difference in FSH bioavailability from IM and SC injection sites. DESIGN Menotropin was injected into either an IM or SC site in women undergoing ovarian suppression with leuprolide acetate. Serial serum samples were obtained over 96 hours. SETTING Academic tertiary care institution. PATIENTS Seven volunteer cycling women. MAIN OUTCOME MEASURES Follicle-stimulating hormone, LH, and E2 were determined in serial serum samples. RESULTS Peak serum FSH levels were higher and occurred earlier after IM injection than after SC injection. Computed absorption rate constants for FSH after IM and SC injection differed significantly. CONCLUSIONS The pharmacokinetics of FSH differ after a single IM or SC injection.

Relative efficiency of therapeutic donor insemination using a luteinizing hormone monitor

A prospective randomized study was performed to evaluate the use of a urinary luteinizing hormone (LH) detection kit with 1 insemination as compared with 2 alternate day inseminations with timing based on previous cycle length and basal body temperature changes. The study involved 60 patients who underwent a total of 264 therapeutic donor insemination cycles using cryopreserved semen specimens. Patients alternated LH-kit timed cycles with cycles timed by non-LH methods for a total of 6 cycles or until pregnancy was achieved. Fecundability rates were 12.3% for LH-kit cycles and 5.3% for non-LH method cycles. The difference in outcome was not statistically significant. However, when the LH kit plus 1 insemination was compared with 2 inseminations timed by conventional methods, there appeared to be a distinct monetary and time expenditure advantage. These findings suggest that sufficient advantage may be derived from use of an LH kit to recommend its use on a routine basis for the timing of therapeutic donor insemination.

Treatment of Dysmenorrhoea and Premenstrual Syndrome with Non-Steroidal Anti-Inflammatory Drugs

SummaryThe menstrual cycle is associated with 2 potentially incapacitating events: dysmenorrhoea and premenstrual syndrome. Although substantial evidence has accumulated to indicate that excessive endometrial production of prostaglandin F2α is the major underlying cause of painful menstruation, correspondingly little is currently known about the basic aetiology of the premenstrual syndrome. Non-steroidal anti-inflammatory drugs have been used to alleviate the discomfort of both entities, and while these agents have come to assume a primary role in the treatment of dysmenorrhoea, a body of evidence substantiating their efficacy in premenstrual syndrome has yet to be developed.