Bronte A. Stone

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.

Age thresholds for changes in semen parameters in men.

OBJECTIVE To determine whether age thresholds for elements of semen quality exist. DESIGN Retrospective analysis (covariance and point-change analysis) of results of 4,822 semen analyses and 259 fluorescence in situ hybridization (FISH) analyses. SETTING Reference laboratory within an infertility clinic. PATIENT(S) A total of 5,081 men aged 16.5-72.3 years. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Ejaculate volume, sperm concentration, sperm motility, sperm motion parameters, strict morphology, and results of FISH analysis. RESULT(S) Measured parameters of ejaculates did not change before 34 years of age. Immediately thereafter, total sperm numbers (and total motile) declined. Sperm concentration and the proportion of sperm of normal morphology declined after 40 years. Sperm motility and progressive parameters of motile sperm fell after 43 years and ejaculate volume after 45 years. The ratio of Y:X-bearing sperm in ejaculates decreased only after 55 years. CONCLUSION(S) Our findings project a declining likelihood of pregnancy following intercourse with men >34 years old, independent from the womans age and increasing with advancing age. Age-related mechanisms associated with this oligoasthenoteratozoospermic progression are discussed.

Suboptimal laboratory conditions can affect pregnancy outcome after embryo transfer on day 1 or 2 after insemination in vitro

We have demonstrated that the replacement of pronuclear stage human embryos on the day after insemination in IVF-ET results in a pregnancy rate as good as, if not better than, the rate after ET on day 2. The pregnancy rate appears to be influenced by the culture environment used for the gametes. We would recommend that ET be undertaken as soon as possible after insemination on day 1 so that if suboptimal culture conditions are present, they do not have sufficient time to affect the viability of the embryos and reduce the subsequent chance of pregnancy after replacement. If culture conditions have been optimized there is no difference in pregnancy rate after embryo transfer on day 1 or day 2 and one can then replace embryos on either day and expect the pregnancy rate obtained in either case to be similar.

Ovarian responses to menopausal gonadotropins in groups of patients with differing basal growth hormone levels

OBJECTIVE To investigate the relationship between endogenous serum levels of human growth hormone (hGH) and ovarian response to human menopausal gonadotropins (hMG). DESIGN Retrospective analysis of patient response to hMG. SETTING Center for assisted reproductive technology. PATIENTS Eighty women who had undergone controlled ovarian hyperstimulation with hMG. Basal levels of hGH in sera from 40 of these patients were less than 5.0 microIU/mL (low hGH), values for the remaining 40 were greater than 5.0 microIU/mL (high hGH). Levels of hGH in day 2 sera were analyzed against numbers of oocytes recovered in an additional 182 patients. MAIN OUTCOME MEASURES Serum estradiol (E2) levels and numbers of oocytes recovered at oocyte pick-up. RESULTS Average (+/- SE) levels of hGH in sera of high-hGH and low-hGH patients were 10.2 +/- 0.6 and 2.47 +/- 0.3 microIU/mL, respectively (P less than 0.05). Respective peripheral levels of insulin-like growth factor-I were 105.3 +/- 2.9 and 97.2 +/- 2.8 ng/mL. Levels of E2 in serum of high-hGH patients exceeded respective (P less than 0.05) low-hGH values throughout folliculogenesis, and more oocytes were recovered from high-hGH patients (8.1 +/- 0.9 versus 4.7 +/- 0.5 for low-hGH patients; P less than 0.05). Serum progesterone values did not differ. Higher day 2 hGH levels were associated with higher numbers of oocytes recovered after controlled ovarian hyperstimulation. CONCLUSIONS The present findings indicate that endogenous hGH may augment gonadotropins during follicle recruitment and during multiple folliculogenesis in women. The phase of maximum ovarian sensitivity to hGH/gonadotropin synergism and the nature of synergism remain unclear.

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%).

Levels of lnterleukin-2 Receptor in Serum of Patients During the Menstrual Cycle and Following Embryo/Gamete Transfer

ABSTRACT: In an attempt to establish whether nidation elicits a measureable systemic immunologic response in vivo, levels of interleukin‐2 receptor (IL‐2R) have been determined in serum drawn from 34 pregnant patients (IUP) immediately before embryo/ gamete transfer, and 7 and 14 days later. For comparison, these same values were determined for 41 subjects who did not conceive, and for 18 who spontaneously aborted (SAB) during the first trimester of gestation. Serum IL‐2R values were near 320 U/ml and did not differ between days within outcomes, or within days between outcomes. Furthermore, levels of IL‐2R and β‐hCG in serum were not interrelated on days 7 or 14 of pregnancy (SAB or IUP). Serum IL‐2R levels did not change during the menstrual cycle. The present results appear to traverse presumptive elements of existing hypotheses of “placental immunotropism.”

Presented at the Fifty-ninth Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, Ojai, California, October 1118, 1992.

Objectives: We determined the effect of embryo transfer, zygote intrafallopian transfer, and frozen embryo transfer on clinical outcomes after surrogate gestational transfers. Study Design: Prospective randomization was carried out. Results: Forty-five infertile couples were matched with a gestational surrogate carrier and underwent 81 cycles of embryo transfer with various assisted reproductive technologic procedures. Nineteen cycles produced a clinical pregnancy, with delivery in 15 of 81 cycles (18.5% live-birth rate). Fifteen of the 45 couples (33%) had a child from the surrogate gestational carrier program. Conclusion: No significant differences in clinical outcome were observed on the basis of the type of procedure performed or the age of the patient.

Numbers and quality of oocytes after induction of multiple folliculogenesis in women and in mice with different lots of human menopausal gonadotropins.

OBJECTIVE To develop a murine in vivo bioassay that is sensitive to inherent variability of hMG. DESIGN Female F1 hybrid mice were mated after injection with fixed dosages of each of four lots of hMG. Oocytes/embryos were collected and monitored during 5 days of culture. Outcome measures were compared with retrospective outcomes of ovarian stimulation of women with the same hMG lots. The bioassay was then used to compare biopotencies of six different lots of hMG. SETTING Center for assisted reproductive technology. INTERVENTIONS None. PATIENTS Outcomes of controlled ovarian stimulation and IVF were retrospectively analyzed from 43 patients. MAIN OUTCOME MEASURES Numbers of oocytes/embryos recovered, numbers fertilized, and numbers progressing beyond fertilization. RESULTS Differences in biopotencies of hMG lots in the murine in vivo bioassay were consistent with differences in outcomes of patients treated with the same hMG lots during controlled ovarian stimulation. Bioassay outcomes also differed between different lots of hMG. CONCLUSION The bioassay described in this study is sensitive to between-lot differences in hMG that affect follicle recruitment and oocyte quality in women (and in mice). In this respect, the bioassay could be of value in screening hMG lots, before its exploitation in a patient population. One such application is explored.

Gonadotropin and Estradiol Levels During Ovarian Stimulation in Women Treated With Leuprolide Acetate

&NA; Levels of FSH, LH, and estradiol (E2) were measured in the serum of 209 gonadotropin‐releasing hormone analogue‐treated women and in 202 control subjects during the final 5 days of ovarian stimulation in our in vitro fertilization program. Levels of FSH and E2 in serum of gonadotropin‐releasing hormone analogue‐treated subjects significantly exceeded control values during the sampling period, whereas LH levels were significantly lower. Concentrations of E2 in serum of gonadotropin‐releasing hormone analogue‐treated and control subjects were similar when corrected for differences in numbers of follicles aspirated at oocyte retrieval (mean of 8.9 and 7.2 follicles per subject, respectively). Pregnancy rates by diagnostic ultrasound were 18 and 11%, respectively, a statistically significant difference. (Obstet Gynecol 73:990, 1989)

Casting for determinants of blastocyst yield and of rates of implantation and of pregnancy after blastocyst transfers

OBJECTIVE To identify determinants of blastocyst yield, implantation rate, and pregnancy outcome. DESIGN Retrospective analysis of outcomes of 1,653 cycles of IVF. SETTING Private infertility clinic. PATIENT(S) Couples presenting to an infertility clinic for IVF. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Blastocyst yield, implantation rate, and pregnancy. RESULT(S) Of a broad array of potential determinants, only the total numbers of oocytes retrieved and properties of day 3 embryos were consistently predictive of blastocyst formation. Relative to numbers of oocytes fertilized by intracytoplasmic sperm injection (ICSI), yields of quality blastocysts were highest in cycles in which <10 oocytes were retrieved. Blastocyst yield was closely linearly correlated with average numbers of blastomeres in embryos on day 3. As oocyte yields rose, average grades and the implantation potential of the blastocysts selected for transfer increased by approximately 0.015 and 0.15%, respectively, for each additional oocyte. Independently, the implantation potential of blastocysts decreased 1.1% for each advancing year in age of the oocyte provider, and, for autologous transfers, uterine receptivity declined an additional 0.6% per year. Higher yields of blastocysts from cycles with high oocyte numbers afforded better selection of blastocysts for transfer, supporting higher overall implantation and pregnancy rates. CONCLUSION(S) While the proportion of fertilized oocytes that progressed to quality blastocysts diminished as numbers of recovered oocytes rose, rates of implantation and pregnancy after transfer of the selected best blastocysts increased. The age of the oocyte provider and oocyte yields independently impacted blastocyst implantation potential and uterine receptivity after controlled ovarian hyperstimulation, ICSI, and blastocyst transfer.