Richard P. Dickey

Comparison of the sperm quality necessary for successful intrauterine insemination with World Health Organization threshold values for normal sperm

OBJECTIVE To compare World Health Organization threshold values for normal sperm with the initial sperm quality necessary for successful IUI. DESIGN Retrospective study. SETTING Private fertility clinic. PATIENT(S) One thousand eight hundred forty-one couples undergoing 4,056 cycles of IUI. INTERVENTION(S) Intrauterine insemination. MAIN OUTCOME MEASURE(S) Relation of initial sperm quality to fecundity. RESULT(S) Progressive motility and total motile sperm count were the initial sperm characteristics most closely related to pregnancy on discriminant analysis. The per-cycle pregnancy rate averaged 11.1% during the first three IUI cycles. Pregnancy rates were > or = 8.2% per cycle when the initial sperm values were a concentration of > or = 5 X 10(6)/mL, a total count of > or = 10 X 10(6), progressive motility of > or = 30%, or a total motile sperm count of > or = 5 x 10(6). Minimal increases in fecundity occurred when initial values were greater than these threshold levels. The lowest initial values that resulted in pregnancy were a concentration of 2 x 10(6)/mL, a total count of 5 x 10(6). motility of 17%, and a total motile sperm count of 1.6 X 10(6). Pregnancy rates were <3.6% when initial values were between the threshold levels and the lowest levels. CONCLUSION(S) The sperm quality that is necessary for successful IUI is lower than World Health Organization threshold values for normal sperm. Intrauterine insemination is effective therapy for male factor infertility when initial sperm motility is > or = 30% and the total motile sperm count is > or = 5 X 10(6). When initial values are lower, IUI has little chance of success.

Effect of diagnosis, age, sperm quality, and number of preovulatory follicles on the outcome of multiple cycles of clomiphene citrate-intrauterine insemination

OBJECTIVE To determine how diagnosis, age, sperm quality, and number of preovulatory follicles affect pregnancy rates when multiple cycles of clomiphene citrate (CC)-IUI are performed. DESIGN Fifteen-year prospective observational study. SETTING Private infertility clinic. PATIENT(S) Three thousand, three hundred eighty-one cycles of husband or donor IUI. INTERVENTION(S) Ovulation induction with CC and IUI. MAIN OUTCOME MEASURE(S) Per-cycle pregnancy rate (PR), cumulative pregnancy rate (CPR). RESULT(S) Pregnancy rates remained constant through four cycles, then fell significantly for diagnoses other than ovulatory dysfunction. Mean PRs for cycles 1-4 were significantly lower for patients with the following characteristics: age >/=43 years, poor semen quality, single preovulatory follicles, and diagnoses other than ovulatory dysfunction. Additional cycles of CC-IUI compensated for low PRs because of age, semen quality, or number of follicles. After four cycles, CPRs were 46% for ovulatory dysfunction; 38% for cervical factor, male factor, and unexplained infertility; 34% for endometriosis; and 26% for tubal factor. After six cycles, CPRs were 65% for ovulation dysfunction, 35% for endometriosis, and unchanged for other diagnoses. CONCLUSION(S) Clomiphene citrate-intrauterine insemination should be performed for a minimum of four cycles. Additional cycles of CC-IUI can compensate for low pregnancy rates due to age, semen quality, or follicle number in patients with ovulation dysfunction.

Gonadal hormones and cognitive performance

The relation of gonadal hormones to cognitive performance was studied in females with ovulatory menstrual cycles, females on oral contraceptives, and males. For the females with the ovulatory menstrual cycles, the highest performance on simple repetitive tasks and the lowest performance on tasks requiring inhibition occurred in the ovulatory phase. Serum estradiol was found to be related to test performance.

Relationship of follicle numbers and estradiol levels to multiple implantation in 3,608 intrauterine insemination cycles

OBJECTIVE To determine the relationship of follicle numbers and estradiol (E(2)) levels to multiple implantations in human menopausal gonadotropin (hMG) and clomiphene citrate (CC) cycles. DESIGN Fifteen-year prospective study. SETTING Private infertility clinic. PATIENT(S) Women who underwent 3608 cycles of husband or donor intrauterine insemination (IUI). INTERVENTION(S) Ovulation induction (OI) with CC, hMG, or CC+hMG. MAIN OUTCOME MEASURE(S) Pregnancy and multiple implantations. RESULT(S) Triplet and higher-order implantations-but not twin implantations-were related to age, E(2) levels, and number of follicles > or = 12 mm and > or = 15 mm, but not number of follicles > or = 18 mm, in hMG and CC+hMG cycles. For patients less than 35 years old, three or more implantations tripled when six or more follicles were > or = 12 mm, in CC, hMG, and CC+hMG cycles, and when E(2) was > or = 1000 pg mL in hMG and CC+hMG cycles. For patients 35 or older, pregnancy rates in hMG and CC+hMG cycles doubled when six or more follicles were > or = 12 mm, or E(2) levels were >1000 pg mL, whereas 3 or more implantations were not significantly increased. CONCLUSIONS Withholding hCG or IUI in CC, hMG, and CC+hMG cycles when six or more follicles are > or = 12 mm may reduce triplet and higher-order implantations by 67% without significantly reducing pregnancy rates for patients under 35 years of age.

Comparison of fecundability with fresh and frozen semen in therapeutic donor insemination

A series of 401 therapeutic donor insemination (TDI) cycles was analyzed for determining the effect on fecundability of fresh versus cryopreserved semen, the number of inseminations per cycle, recipient age, and the reproductive health of the TDI recipient. We followed a protocol in which inseminations were performed during the periovulatory period determined by urinary luteinizing hormone surge or ultrasound-timed human chorionic gonadotropin injection. The minimum standard for insemination with fresh or cryopreserved semen was a total of 40 X 10(6) grade 3 sperm. We found no decreased fecundability when using frozen semen, rather than freshly ejaculated specimens. The number of inseminations per cycle did not affect the pregnancy outcome after TDI. The reproductive health of the recipient had a significant effect on the pregnancy rate. Fecundability was 15.6% for healthy women, as compared with 6.7% for women with a diagnosis of moderate, severe, or extensive endometriosis, pelvic adhesions, tubal disease, or ovulatory dysfunction. To avoid transmission of human T-lymphotropic virus type III from sperm donor to TDI recipient, we have recently utilized an exclusively frozen TDI program. With well-timed inseminations of 40 X 10(6) grade 3 motile sperm, we have been able to attain pregnancy rates similar to those previously obtained with fresh samples.

The acute effect of hysterectomy on ovarian function

The acute effect of abdominal and vaginal hysterectomy on the ovarian production of estradiol-17-beta (E2) and progesterone (P) was studied in a group of patients undergoing hysterectomy for various gynecologic indications. Plasma levels of steroids as well as gonadotropins (FSH and LH) were measured by RIA. There was a significant but transient drop of plasma E2 during the follicular phase and of plasma E2 and P during the luteal phase, following hysterectomy. No significant variations in the steroid plasma levels were found in a control group of patients undergoing laparoscopy for diagnostic purposes. No changes were noted in either group in the plasma levels of gonadotropins. The changes seen appear to be related to the surgical manipulation in the ovarian region rather than to the type of hysterectomy performed or the stress of surgery.

Strategies to reduce multiple pregnancies due to ovulation stimulation

OBJECTIVE To review factors associated with high-order multiple births (HOMB) due to ovulation induction (OI) and the efficacy of strategies to reduce their occurrence. DESIGN Retrospective analysis of published studies of OI with intrauterine insemination (IUI) where patient and cycle characteristics were fully documented. RESULT(S) High-order multiple pregnancies (HOMP) were positively related to use of high doses of gonadotropin, number of 7-10 mm preovulatory follicles, and E(2), and inversely related to age and number of treatment cycles. Strategies successful in reducing HOMP include: use of clomiphene (CC) before gonadotropins, minimal gonadotropin doses, cancellation for more than three follicles >10-15 mm, and aspiration of excess follicles. Depending on the strategy used, 5%-20% of cycles may be canceled but HOMP rates can be less than 2% and pregnancy rates can average 10%-20% per cycle. Pregnancy rates per patient need not be reduced if low doses are continued for 4-6 cycles. CONCLUSION(S) High-order multiple pregnancies due to OI can be reduced to 2% or less by less aggressive stimulation without reducing overall chances of pregnancy for most patients.

Observations on the Mechanism of Action of Clomiphene (MRL-41)

Serial follicle stimulaint hormone (FSH) and luteinizing hormone (LH) determinations (by the methods of Steelman and Pohley and Parlow respectively) in 4 23-53 year old anovulatory patients given short-term clomiphene treatment (100-400 mg orally/day for 6 days) were employed in studying the mechanism of clomiphene action. Serial determinations of 3 estrogens (estrone estradiol and estriol) were also determined using thin-layer absorption chromatography before Kober color development. FSH levels rose in all cases during or immediately following clomiphene therapy. LH did not rise prior to a rise in estrogens. The estradiol fraction was found to contain at least 3 different components. During clomiphene therapy the estradiol fraction fell. Since the estradiol fraction was composed of 2 compounds in addition to estradiol and since it fell during treatment it was postulated that it was the unidentified estrogens whose excretion had decreased. It was suggested that this fall in unidentified estrogens may be responsible for the increase in FSH release observed during treatment.

Polycystic ovarian syndrome and the metabolic syndrome.

Polycystic ovarian syndrome (PCOS), first described in 1937, was defined by specific ovarian histopathology and a constellation of signs and symptoms. Through the years, the etiology remained elusive, with heated debates focusing in turn on the ovary and then the pituitary as the causative agents. In the last several decades, it has become clear that insulin resistance makes up a very important component of this syndrome. With this knowledge, new therapies have emerged along with the realization that PCOS and the metabolic syndrome are closely related through their shared insulin resistance. In this review, the diagnosis, pathophysiology, and therapy of PCOS are discussed and upon this background, those areas held in common by PCOS and the metabolic syndrome are explored.

Estrogen potency of oral contraceptive pills

The estrogen potencies of 9 oral contraceptive pills, Enovid-E, Enovid-5, Ovulen, Demulen, Norinyl+80, Norinyl+50, Ovral, Norlestrin 1 mg. and Norlestrin 2.5 mg., were determined by bioassay. Relative estrogen potency was determined by analysis of variance. Enovid-5, the most estrogenic compound, had a potency of 4.88 compared to ethinyl estradiol, 50 mcg. equal 1.00; Ovral, the least estrogenic compound, had a potency of 0.81, a sixfold difference. Estrogen potencies at a fractional dose of 0.00155 correlate with reports of the incidence of minor side effects and thromboembolic disease. The effect of progestins on estrogen potency was purely additive (norgestrel and norethynodrel), purely antagonistic, or additive at low concentrations and antagonistic at high concentrations (norethindrone, norethindrone acetate, and ethynodiol diacetate). These results suggest that pills with a greater margin of safety might be developed by utilizing greater ratios of progestin to estrogen. In addition, differences in relative estrogen potency of oral contraceptive pills may be used as a basis for better clinical selection.