David N. Curole

Relationship of endometrial thickness and pattern to fecundity in ovulation induction cycles: effect of clomiphene citrate alone and with human menopausal gonadotropin

OBJECTIVE To determine if preovulation endometrial thickness or pattern are related to fecundity and to use of clomiphene citrate (CC) or hMG in IUI. DESIGN Prospective ultrasound evaluation the day of hCG after CC alone (n = 197), hMG alone (n = 49), concurrent hMG or sequential CC and hMG (n = 205), and no medications (n = 23). SETTING Private fertility clinic. PATIENTS Two hundred seventy-one patients undergoing 474 cycles of IUI. MAIN OUTCOME MEASURES Endometrial thickness, pattern, per cycle fecundity, and continuing pregnancy. RESULTS Endometrial thickness was related to fecundity and continuing pregnancy. No pregnancies occurred when thickness was < 6 mm. The continuing pregnancy rate was 12.6% when thickness was > or = 9 mm, compared with 6.9% when thickness was 6 mm to 8 mm. Endometrial pattern was unrelated to pregnancy. Average endometrial thickness was decreased when hMG and CC were used in combination (7.9 mm) compared with hMG alone (9.4 mm). Endometrial thickness was negatively related to CC dose and positively related to the day of hCG administration by ANOVA. CONCLUSIONS Endometrial thickness the day of hCG administration is prognostic of fecundity and continuing pregnancy in cycles of ovulation induction.

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.

Relationship of follicle number and other factors to fecundability and multiple pregnancy in clomiphene citrate-induced intrauterine insemination cycles*†

OBJECTIVE To determine characteristics associated with pregnancy and multiple gestation after clomiphene citrate (CC)-intrauterine insemination (IUI). DESIGN Prospective study of all patients undergoing CC-IUI between January 1, 1983 and December 31, 1989. SETTING Private fertility clinic. PATIENTS Eight hundred forty-nine patients undergoing 1,974 cycles of CC-IUI. MAIN OUTCOME MEASURES Relationship between number and size of preovulatory follicles, age, additional infertility diagnosis, medication, and initial semen quality to fecundity, birth, and multiple gestation. RESULTS Uncorrected, per cycle fecundity was 7.2%. The number of follicles greater than or equal to 12 mm (r = 0.055, P less than 0.05) was and the number greater than or equal to 15, 18, and 21 mm was not correlated with fecundity. Endometriosis with (P = 0.013) or without (P less than 0.0005) tubal adhesions and tubal adhesions alone (P = 0.005), decreased fecundability by 50%. Initial semen quality did not affect fecundity, unless semen concentration was less than 5 x 10(6)/mL or motility was less than 20%. Multiple pregnancy was not associated with the dose of CC, use of human chorionic gonadotropin, or number of follicles. CONCLUSIONS Multiple pregnancy was unrelated to follicle numbers or to CC dose. The highest birth rates after CC-IUI occurred when initial sperm concentration was greater than or equal to 5 x 10(6)/mL, motility was greater than or equal to 20%, and no endometriosis or adhesions were present.

Fertilization of human oocytes by microinjection of human sperm aspirated from the caput epididymidis of an individual with obstructive azoospermia

Aspiration of spermatozoa from the caput region of the epididymis was performed, due to obstructive azoospermia. When all inseminated oocytes failed to fertilize in vitro, immotile spermatozoa were microinjected into the perivitelline space to achieve fertilization. Of six oocytes microinjected, one exhibited two normal pronuclei and two polar bodies and was subsequently transferred to a fallopian tube of the wife. One oocyte arrested at syngamy, while two additional oocytes cleaved to four cells each. The remaining two were damaged during microinjection. Although the patient did not conceive, this report provides evidence that (1) spermatozoal motility is not required for successful pronuclear formation when microinjection is performed, and such immotile sperm are not necessarily “dead,” and (2) this further corroborates that caput epididymal spermatozoa can participate in the subzonal events of fertilization and that, in the human, exposure of spermatozoa to the distal epididymal milieu may not be a requisite to achieve fertilizing capacity.

Pregnancies in cancelled gamete intrafallopian transfer cycles.

Forty-four percent of started GIFT cycles were cancelled. Insemination and intercourse in the cancelled cycles yield a 23% and 10% pregnancy rate, respectively.

The occurrence of ectopic pregnancy with and without clomiphene citrate use in assisted and nonassisted reproductive technology

An eleven-year review of treatment records of patients who became pregnant as a result of infertility treatment (n=3692) was conducted. All records were examined to determine whether clomiphene citrate (CC) was used in the cycle of conception and whether or not an ectopic pregnancy occurred. Data were additionally analyzed for the incidence of ectopic pregnancy with and without assisted reproductive technology (ART). The incidence of ectopic pregnancy was similar between CC (3.4%) and non-CC (3.4%) treatment groups receiving non-ART treatment. For non-ART treatments, tubal disease and severe endometriosis resulted in an increase in ectopic pregnancies independent of CC use. The incidence of ectopic pregnancy in patients receiving CC + human menopausal gonadotropin (hMG) for in vitro fertillization (5.4%) and gamete intrafallopian transfer (3.1%) was similar compared to ART treatments with hMG alone. The incidence of ectopic pregnancy was more closely associated with infertility diagnosis rather than CC use.

Laparoscopic implant of Gore-Tex surgical membrane

One of the major postoperative complications of reproductive surgery is the formation of adhesions. 1, 2 Over the past several decades a number of methods have been explored to solve this problem, g, 4 Recently there has been renewed interest in covering the damaged peritoneal surface with an absorbable or nonabsorbable barrier as a means of preventing adhesions after fertility-enhancing surgery. Currently two barriers are commercially available for clinical use: Interceed Absorbable Adhesion Barrier (Ethicon, Somerville, NJ), which is composed of oxidized regenerated cellulose, and the Gore-Tex Surgical Membrane (W. L. Gore & Associates, Inc., Flagstaff, AZ), constructed of expanded polytetrafluoroethylene (e-PTFE). Interceed has been investigated both experimentally and clinically and has proved effective in some circumstances. 5, 6 Studies also report on the laparoscopic application of Interceed in fertility-enhancement procedures.7, 8 Recent reports, however, have questioned the product s degree of effectiveness and raised concern about possible residual effects it may have on peritoneal tissue? 11 GoreTex Surgical Membrane has been indicated for use in peritoneal reconstruction since 1983, and experimental and clinical reports describe its effectiveness in preventing adhesion formation. 12-14 Interceed is an absorbable material that is phagocytized by macrophages within 1 month. Gore-Tex Surgical Membrane is nonabsorbable and is intended to be a permanent implant. Since all published reports on the clinical application of the Gore-Tex membrane discuss implantation by laparotomy, ~g, 14 the ease of use of this product in laparoscopic surgery is of particular interest. Moreover, because of its permanence, its long-term safety and effectiveness merit examination. A prospective, multicenter clinical study was undertaken to evaluate the ease of using Gore-Tex Surgical Membrane laparoscopically.

Correlation of pregnancy after gamete intrafallopian transfer with fertilization and cleavage of sibling oocytes

In this study, GIFT resulted in a 44% pregnancy rate. When excess oocytes fertilized and developed to the blastocyst stage, the pregnancy rate was 78%. The continuing pregnancy rate was increased from 31% to 55% when sibling blastocysts developed.

Relationship of follicle number, serum estradiol, and other factors to birth rate and multiparity in human menopausal gonadotropin-induced intrauterine insemination cycles**Presented at the 38th Annual Meeting of the Pacific Coast Fertility Society, Scottsdale, Arizona, April 25 to 29, 1990.

OBJECTIVE To determine the characteristics associated with pregnancy and multiple gestation after human menopausal gonadotropin intrauterine insemination (hMG-IUI). DESIGN Prospective study of all patients undergoing hMG-IUI between January 1, 1984 and December 31, 1989. SETTING University affiliated private clinic. PATIENTS Four hundred twenty-four infertility patients undergoing 779 cycles of hMG-IUI. MAIN OUTCOME MEASURES The relationship between estradiol (E2), number and size of follicles, age, and initial semen quality on pregnancy and multiple gestations in hMG-IUI cycles. RESULTS The number of follicles greater than or equal to 12 mm was correlated with births and predicted all multiple births (r = 0.140, P less than 0.001). The corrected birth rate was 25.8% for age less than 35 and 14.0% for age greater than or equal to 35 when four or more follicles were greater than or equal to 12 mm. The uncorrected clinical pregnancy rate (PR) and birth rate were 12.8% and 10.5%, respectively. Decreased births were associated with tubal adhesions alone (P less than 0.03) or with endometriosis (P less than 0.002), more than four cycles of treatment (P = 0.01), initial sperm count less than 5 x 10(6) per mL (P less than 0.01), initial sperm motility less than 30% (P less than 0.002), and age greater than or equal to 35 (P less than 0.01). Estradiol was correlated with birth rate (r = 0.160, P less than 0.001), which increased from 3.6% when E2 was less than 500 pg/mL to 19.6% when E2 was greater than or equal to 2,500 pg/mL. CONCLUSIONS The outcome of hMG-IUI is related to the number of follicles greater than or equal to 12 mm, to E2, and to age. Optimal PRs from hMG-IUI require mild ovarian hyperstimulation.