Richard P. Marrs

An alternate approach to controlled ovarian hyperstimulation in “poor responders”: pretreatment with a gonadotropin-releasing hormone analog *

Pharmacologic hypophysectomy was induced with a subcutaneous injection of leuprolide acetate before the administration of exogenous gonadotropins for multiple follicle development in 27 women who had previously responded poorly to conventional controlled ovarian hyperstimulation (COH). Pituitary desensitization occurred within 6 days and concurrent COH with exogenous gonadotropins resulted in an enhanced yield of oocytes in comparison to previous COH attempts (P less than 0.05). Fertilization and pregnancy rates also were higher with gonadotropin-releasing hormone agonist (GnRHa) treatment (P less than 0.01). The administration of leuprolide acetate effectively suppressed endogenous gonadotropin secretion when initiated in the follicular or luteal phase of the menstrual cycle. GnRHa therapy can appreciably facilitate the management of gonadotropin therapy, and increase the probability of oocyte collection and pregnancy.

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.

The use of potassium-titanyl-phosphate laser for laparoscopic removal of ovarian endometrioma

From January 1989 through January 1990, 31 patients thought to have ovarian endometrioma at ultrasonography were treated by operative laparoscopy and potassium-titanyl-phosphate laser. The endometriomas ranged from 2 to 9.2 cm in diameter by preoperative transvaginal ultrasonography. The operative procedure used was a three-puncture technique with a 600 micron fiber attached to a potassium-titanyl-phosphate laser. The power setting was 10 W with a continuous pulse. In all cases endometriomas were opened, drained, and irrigated, and the potassium-titanyl-phosphate laser was used to vaporize or remove the entire cyst lining. The ovarian edges were inverted with the laser at the end of the procedure. With one exception, there was no recurrence of endometrioma at 1, 3, and 6 months after the procedure, on the basis of transvaginal ultrasonography or laparoscopy. In one case, 4 months after the initial laparoscopic procedure, exploratory laparotomy was performed for resection of a large, recurrent endometrioma. The use of the potassium-titanyl-phosphate laser allows the laparoscopic surgeon an aggressive approach to ovarian endometriomas that in the past necessitated exploratory laparotomy.

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.

Occurrence of a spontaneous luteinizing hormone surge in superovulated cycles—predictive value of serum progesterone

A preovulatory increase in serum progesterone (P) precedes the occurrence of an endogenous luteinizing hormone (LH) surge in a majority of women. This study evaluates whether a single daily measurement of serum P could reliably identify a spontaneous LH surge in women undergoing controlled ovarian hyperstimulation. Eighty-four infertile women received either clomiphene citrate and human menopausal gonadotropin (hMG), or hMG alone. Serum P levels were increased significantly the morning of the day of an endogenous LH surge (P less than 0.01). A 2-fold rise in the serum P levels was associated with a predictability of 64.4% of a LH surge; however, a 4-fold increase in serum P could accurately predict a spontaneous endogenous LH discharge in 93.3% (P less than 0.001) of cases.

Advanced-stage ovarian carcinoma presenting during infertility evaluation

Fecundity has been extended to the menopause by advances in assisted reproductive techniques. The incidence of ovarian cancer increases with age, and an increased risk of ovarian cancer has been associated with incessant ovulation and infertility. The increased risk of ovarian cancer in older infertility patients must be kept in mind when evaluating these patients so that this diagnosis is not overlooked or delayed.

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.”