Joyce M. Vargyas

Determinants of the outcome of intrauterine insemination: Analysis of outcomes of 9963 consecutive cycles

OBJECTIVE Our aim was to determine which factors influence the effectiveness of intrauterine insemination. STUDY DESIGN This article is a retrospective statistical analysis of outcomes of 9963 consecutive intrauterine insemination cycles. RESULTS Patient age was the main determinant of pregnancy outcome (analysis of variance F ratio = 29, P <.0001), followed by the number of follicles at the time of intrauterine insemination (analysis of variance F ratio = 9, P <.0001) and sperm motility in the inseminate (analysis of variance F ratio = 4, P =.002). A total of 18.9% of all patients <26 years old conceived, compared with 13.9% of those 26-30 years old, 12.4% of those 31-35 years old, 11.1% of those 36-40 years old, 4.7% of those 41-45 years old, and 0.5% of patients >45 years old (P <.001). When analyzed by single years, ongoing pregnancy rates after intrauterine insemination remained high through age 32 years. Across all ages and causes of infertility, 7.6% of patients with 1 follicle at the time of intrauterine insemination conceived, compared with 10. 1% with 2, 14.0% with 4, and 16.9% with 6 follicles (P <.01). When ovulation occurred before intrauterine insemination (ie, no visible follicular structures), 4.6% of patients conceived. The likelihood of pregnancy was maximized when motile sperm numbers were >/=4 million and sperm motility was >/=60%. Differences in pregnancy outcomes between sperm processing options were related to differences in sperm motility after processing; use of methods incorporating motility enhancement with pentoxifylline and motile sperm concentration through silica gradients yielded the highest overall pregnancy rates. CONCLUSION When the results of ongoing retrospective analysis of intrauterine insemination outcomes are applied, overall intrauterine insemination pregnancy rates have increased from 5.8% per cycle in 1991 to 13.4% per cycle in 1996, during which time the average age of patients undergoing intrauterine insemination has increased from 36.1 (+/-0.2) to 39.2 (+/-0.1) years.

Correlation of ultrasonic measurement of ovarian follicle size and serum estradiol levels in ovulatory patients following clomiphene citrate for in vitro fertilization

Ovarian follicle development was investigated in 38 normally cycling women who received clomiphene citrate, 150 mg per day for 5 days, to maximize follicular development. Ultrasonic determination of follicle growth was performed on a daily basis with a real-time sector scanner and correlated with daily concentrations of estradiol (E2) in the peripheral serum as measured by rapid radioimmunoassay. Human Chorionic gonadotropin was given to induce ovulation, and the day of injection was considered day 0. Mean concentrations of E2 reached a maximum of 1,150 +/- 65 pg/ml on day 0. Mean diameter of the dominant follicle increased to 22.1 +/- 0.4 on day 0. When peripheral concentrations of E2 were correlated with diameter and total follicular volume it was found that plasma E2 levels varied, depending on the number of follicles seen on ultrasound examination, with a mean E2 value of 459 +/- 18.9 pg/ml per follicle per day. Multiple growth of follicles occur with artificial induction of ovulation; therefore, the use of ultrasound is an important parameter to assess follicular maturation and the timing of ovulation more precisely.

The effect of different methods of ovarian stimulation for human in vitro fertilization and embryo replacement

Many types of medication regimens have been used to produce ovarian stimulation for in vitro fertilization and embryo replacement. However, few comparative studies have been reported. In this investigation, 105 patients were given either clomiphene citrate alone, human menopausal gonadotropins alone, or a combination of these drugs; and the resulting number of oocytes collected, embryos produced, and pregnancies initiated are reported. The data demonstrate optimal follicle development and fertilization rates with combinations of drugs, rather than the use of a single agent. Further studies are needed to determine whether there is a statistically significant difference in pregnancy rates between groups.

Clinical applications of techniques used in human in vitro fertilization research

Human in vitro fertilization-embryo transfer not only provides an opportunity for pregnancy in women who were previously considered to be sterile, but also provides a unique method by means of which basic reproductive physiology can be investigated. From September, 1981, to September, 1982, 71 women with normal cycles who elected to attempt in vitro fertilization-embryo transfer underwent timed laparoscopy for recovery of oocytes. Oocytes were recovered in 60 patients, with embryo transfer resulting in 50 patients, and normal implantation occurred in nine patients. There was a significant correlation between ultrasound observation of follicle size and serum estradiol levels, thus making ultrasound monitoring of follicular growth during stimulation with clomiphene citrate or human menopausal gonadotropin in anovulatory women clinically useful. The technique of sperm washing employed for in vitro fertilization has now been used with good results for intrauterine insemination in patients with infertility due to a cervical factor or oligospermia. Therefore, the techniques used in human in vitro fertilization-embryo transfer are now clinically applicable for couples with infertility due to causes other than tubal disease.

The effect of time of initiation of clomiphene citrate on multiple follicle development for human in vitro fertilization and embryo replacement procedures

Clomiphene citrate has been utilized for ovarian stimulation for human in vitro fertilization and embryo replacement (IVF-ER) procedures quite successfully. The optimal time and the amount of drug necessary for optimal development have not been identified. In this investigation, 58 patients participating in a human IVF-ER program were stimulated with clomiphene citrate, 150 mg/day for 5 days, beginning on day 3, 4, 5, or 7 of the menstrual cycle. Maximal numbers of oocytes recovered, fertilized, and transferred occurred when stimulation was initiated on the fifth day of the cycle. It is concluded that if clomiphene alone is utilized for multiple follicle development, cycle day 5 is optimal for drug initiation.

A modified technique of human in vitro fertilization and embryo transfer

Forty-seven ovulatory women were treated with a modified technique of human in vitro fertilization and embryo transfer. All patients received clomiphene citrate, 150 mg per day, and follicle development was monitored by real-time ovarian ultrasound and serum estradiol measurement. In the 45 patients who underwent laparoscopy, eight patients were found to have a poor response to clomiphene citrate and were dropped from the treatment cycle. Four additional patients had an endogenous luteinizing hormone increase and did not undergo laparoscopy. Nine patients were found to have inaccessible ovaries at the time of laparoscopy. In patients with accessible ovaries, oocytes were recovered in all cases. Embryo transfers were performed in 72% of patients, and 19% of these transfers resulted in pregnancy. This technique of ovulation monitoring appears to increase oocyte recovery and fertilization rate and subsequent implantation success.

Correlation of transabdominal and transvaginal ultrasound measurements of follicle size and number with laparoscopic findings for in vitro fertilization

This paper compared the use of a transvaginal scanning approach with the conventional transabdominal scanning method. In study I, 15 patients with previous suboptimal abdominal ultrasounds were evaluated in subsequent cycles with both the transabdominal and the transvaginal techniques. With the transvaginal method, improvement was observed in 13 patients (87%). Study II compared both the transabdominal and transvaginal ultrasound measurements of follicle number and size with surgical findings. A high correlation (r = 0.914, P less than 0.001) was demonstrated between the number of follicles visualized by transvaginal sonogram and the number of follicles aspirated. A significant correlation (r = 0.639, P less than 0.001) was also observed between follicular fluid volume and the mean ultrasound follicle diameter determined transvaginally.

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).

Successful pregnancies from cryopreserved human embryos produced by in vitro fertilization

Sixty-three embryos produced after in vitro fertilization in 30 infertile couples were frozen and stored. Dimethylsulfoxide was used as a cryoprotectant and embryos were frozen from the two-cell stage to early blastocyst development. Replacement occurred during spontaneous ovulatory cycles 2 to 15 months after embryo freezing. Embryo replacement was performed 3 to 6 days following identification of the luteinizing hormone surge in the spontaneous cycle. Thirty-five embryos were replaced into 25 women and two viable pregnancies resulted.

Responses of patients to different lots of human menopausal gonadotropins during controlled ovarian hyperstimulation

Responses of patients treated with different lots of human menopausal gonadotropin (hMG) during controlled ovarian hyperstimulation were analyzed. Levels of luteinizing hormone (LH) in serum varied between groups of patients treated with different hMG lots, serum follicle-stimulating hormone (FSH) levels did not differ. In the analysis of levels of estradiol (E2) in serum of patients pretreated with leuprolide acetate (gonadotropin-releasing hormone analog; GnRH-a), there was an interaction between hMG lot and day of stimulation. E2 levels/follicle also diverged between hMG batches as ovum pick-up approached. Within the groups of patients pretreated with GnRH-a, serum FSH/LH ratios varied between 5 and 20, with a batch x day interaction. Ongoing pregnancy rates in the hMG-treatment groups ranged between 0/24 and 7/33 (21%).