Autoantibodies and infertility: a review of the literature.

The role that autoantibodies play in infertility remains uncertain. There are conflicting data regarding the prevalence of autoantibodies in women with endometriosis. Certainly no one has demonstrated an association between the presence of antibodies in women with endometriosis and infertility. Despite intensive study, there is also no consensus on a role of autoantibodies to the zona pellucida as a cause of infertility. Recently, much attention has been focused on autoantibodies and infertility particularly with regards to phospholipid antibodies and their effect on IVF success rates. The literature suggests that women with infertility have an increased prevalence of phospholipid antibodies compared to fertile women. However, the presence of these antibodies has not been associated with a worsened prognosis for IVF cycles. Many questions remain to be answered. What is the cause of this apparently increased prevalence of autoantibodies in infertile women? Do these autoantibodies cause infertility or are they merely associated with some other condition which is actually causitive? Finally, can treatment of autoantibodies improve pregnancy rates in infertile couples after IVF or other infertility treatments? The answers to these questions should be sought by carefully conducted trials with appropriate control groups. Subjecting patients to expensive testing and 'treatments' before these answers are known is not consistent with good scientific or medical practice.

The effect of laparoscopic ablation or danocrine on pregnancy rates in patients with stage I or II endometriosis undergoing donor insemination.

The effect of treatment on stages I and II endometriosis was evaluated in 61 women with laparoscopically proven disease who were undergoing therapeutic donor insemination. Only treatment cycles completed after diagnostic laparoscopy were used for analysis. To evaluate fecundity, we performed life-table analysis on 343 treatment cycles of therapeutic donor insemination in 67 patients with stage I or II endometriosis and compared it with 212 cycles in 43 patients with no female infertility factors. Average monthly fecundity and cumulative conception rates over six cycles were calculated for each group. A significant difference was found when patients with laparoscopically proven normal anatomy were compared with those with endometriosis (P = .002). The fecundity did not differ significantly between stage I and stage II endometriosis (P greater than .05). Neither ablation during laparoscopy nor medical treatment with danocrine improved the fecundity of patients with early-stage endometriosis (P greater than .05).

Abnormal findings on hysterosalpingography: effects on fecundity in a donor insemination program using frozen semen.

OBJECTIVE: We sought to evaluate the effect of abnormal baseline hysterosalpingography (HSG) on subsequent fecundity during the first six cycles of treatment. METHODS: Hysterosalpingography was performed on 208 asymptomatic ovulatory women with no history of pelvic disease who were referred for donor insemination. The findings were categorized into five groups: 1) normal study, 2) uterine anomaly or filling defect with bilateral tubal patency, 3) normal uterine anatomy with unilateral tubal patency, 4) normal uterine anatomy with bilateral tubal blockage, and 5) normal uterine anatomy with hydrosalpinx. Subjects in groups 4 and 5 received inseminations only if patency of at least one fallopian tube was demonstrated with laparoscopy. Life-table analysis was performed to calculate the average monthly fecundity and cumulative conception rates for each group. The Mantel-Haenszel test was used to compare group fecundities. RESULTS: A total of 1460 donor insemination cycles were performed. The number of cycles in each group were as follows: group 1, 1173 (80%); group 2, 153 (10%); group 3, 90 (6.2%); group 4, 16 (1.1%); and group 5, 28 (1.9%). None of the patients in group 4 or 5 conceived. The cumulative conception rates in the first three groups were 46, 34, and 40%, respectively, and were not significantly different from one another (P greater than .05). Although a high incidence of uterine filling defects and unilateral tubal blockage was observed (19.2%), the incidence of an abnormal HSG finding that significantly decreased fecundity was only 2.8%. CONCLUSION: In women with no history of tubal or uterine disease, routine HSG before initiation of donor insemination is of limited value for identifying decreased treatment fecundity.

The effect of age on female fecundity.

To determine the relationship between age and female fecundity, 210 women were studied prospectively. The subjects had negative infertility evaluations and were receiving therapeutic donor insemination. Life-table analysis was performed on 751 donor insemination cycles. For comparison, patients were divided into five separate age groups and into two separate groups, ages 19-34 and 35-45. Monthly fecundity and cumulative conception rates were calculated for each group. A significant difference was found when all age groups were compared (P = .05) and when those at or above age 35 and those below age 35 were compared (P less than .05). Frozen semen was used in 92% of all cycles. The average monthly fecundity of all patients treated with frozen semen was 16%. This study confirms a progressive decline in fecundity with age in a completely evaluated group of women undergoing therapeutic donor insemination and demonstrates that frozen semen can yield acceptable fecundity provided sufficient numbers of motile sperm are used for each procedure.

Fertility rates in men with normal semen characteristics: spermatozoal testing by induction of the acrosome reaction and Wright-Giemsa staining for subtle abnormal forms.

Little is known about the fertility potential of semen from men who fulfill the accepted criteria of normal semen quality. We examined retrospectively the fertility rates of semen donors with normal semen quality. Donor performance was evaluated in women who had no known infertility factors or had only ovulatory dysfunction corrected by clomiphene. Cycles of therapeutic donor insemination were monitored for ovulation, and pregnancy outcome was followed up. Pregnancy resulted from therapeutic donor insemination with 21 donors and did not result in pregnancy with five (the range of the percentage of cycles in which pregnancy occurred was zero to 31). The comparison of donor semen analysis characteristics with pregnancy rates indicated that the total number of motile spermatozoa per ejaculate correlated with pregnancy rate (P = .04). Cox proportional hazard regression analysis showed that when the value for percentage of abnormal forms was combined with the total number of motile spermatozoa, a significant negative association was found between abnormal forms and conception (P = .04). Experiments comparing semen from high-fertility donors (top quartile of pregnancy rate) and low-fertility donors (lowest quartile) demonstrated a greater proportion of spermatozoa with inducible acrosome reactions in the high-fertility group (P less than .05). A Wright-Giemsa stain used to detect subtle abnormal forms in spermatozoa did not discriminate between the groups. These data suggest that differences in fertility potential exist among donors, even though all may exceed the accepted criteria for normal semen quality. Differences in the ability of spermatozoa to capacitate or undergo the acrosome reaction may be a mechanism for diminished fertility in donors with normal semen characteristics.

Sonohysterography in premenopausal women with and without abnormal bleeding.

OBJECTIVE: To estimate the prevalence of abnormalities detected by sonohysterography in premenopausal women who were asymptomatic or had abnormal uterine bleeding. METHODS: Standard sonohysterography was done in 100 asymptomatic premenopausal women age 30 and older. The prevalence of uterine abnormalities was recorded and compared with findings in 80 premenopausal women evaluated in our unit for abnormal uterine bleeding. RESULTS: Compared with asymptomatic women, premenopausal women with abnormal uterine bleeding had a higher prevalence of polyps (33 versus 10%), intracavitary myomas (21 versus 1%), and intramural myomas (58 versus 13%). Ten percent of asymptomatic women had polyps, but these polyps tended to be smaller than the polyps found in women with abnormal bleeding (8.5 versus 13.9 mm, P = .064). Polyps were associated significantly with myomas, and both were more common in older premenopausal women. CONCLUSION: Intracavitary lesions and intramural myomas are more prevalent in women with abnormal uterine bleeding than in asymptomatic women, suggesting a causative relationship. However, small endometrial polyps are common and frequently asymptomatic.

The effects of smoking on ovarian function and fertility during assisted reproduction cycles.

OBJECTIVE: To investigate the effects of cigarette smoking on ovarian function and fertility in women undergoing assisted reproduction cycles. METHODS: We assessed the effects of smoking on ovarian function and fertility in a cohort of 499 women. Questionnaires were designed to quantify past smoking exposure and to determine whether the woman was smoking during the treatment cycle. Ovarian function characteristics and pregnancy rates were compared among current smokers, past smokers, and nonsmokers. RESULTS: Compared with nonsmokers, both current and past smokers have reduced gonadotropin-stimulated ovarian function. A history of increasing tobacco exposure was associated with decreasing serum estradiol concentrations, numbers of retrieved oocytes, and numbers of embryos. On average, for every 10 pack-years of cigarette smoking, 2.5 fewer mature oocytes and 2.0 fewer embryos were obtained. Women who smoked during their treatment cycle had approximately a 50% reduction in implantation rate and ongoing pregnancy rate compared with women who had never smoked. Women who quit smoking before their treatment cycle had the same pregnancy rate as nonsmokers. CONCLUSION: Cigarette smoking is associated with a prolonged and dose-dependent adverse effect on ovarian function. Smoking appears to have a more transient toxic effect on fertility, because current smokers, but not past smokers, had a markedly reduced pregnancy rate after treatment cycles compared with nonsmokers. Women should quit smoking before assisted reproduction cycles.

Raloxifene and estrogen effects on quality of life in healthy postmenopausal women: a placebo-controlled randomized trial.

OBJECTIVE: To assess the effects of raloxifene, estrogen, and placebo on quality of life in healthy, asymptomatic, postmenopausal women. METHODS: In a multicenter, double-blind, 12-month study, 398 women were assigned randomly to one of four groups: raloxifene HCl, 60 (n = 97) or 150 mg/day (n = 100); conjugated equine estrogens, 0. 625 mg/day (n = 96); or placebo (n = 105). The Women's Health Questionnaire, a validated quality-of-life instrument for perimenopausal and postmenopausal women, was administered at baseline and 3-month intervals. RESULTS: Overall, quality of life from baseline to end point was preserved equally in all treatment groups. Six domains (depressed mood, somatic symptoms, memory/concentration, sexual behavior, sleep problems, and perceived attractiveness) were unchanged in all groups. Three domains (menstrual symptoms, vasomotor symptoms, and anxiety/fears) were statistically significantly different among groups. Mean scores for menstrual symptoms significantly worsened and vasomotor symptoms significantly improved from baseline to end point in the estrogen group. Mean scores for vasomotor symptoms did not worsen at any point in the raloxifene 60 mg/day group. Mean anxiety/fears scores improved significantly during raloxifene 60 mg/day administration throughout treatment (P <.05), irrespective of previous hormone replacement therapy, baseline estradiol (E2) levels, or years postmenopause. CONCLUSION: Most quality-of-life domains were not affected by treatment with estrogen or raloxifene. Estrogen provided relief from vasomotor symptoms but caused menstrual symptoms. Raloxifene 60 mg/day improved anxiety levels in postmenopausal women.

Reactions of residency directors to primary care requirements in obstetrics and gynecology training.

OBJECTIVE: To determine the opinions of obstetrics and gynecology residency program directors regarding the Residency Review Committee mandate, requires 6 months of primary care training in obstetrics and gynecology. METHODS: A ten-question survey was mailed to the 272 accredited obstetrics and gynecology programs in the United States and Puerto Rico. Program directors were asked about the adequacy of 6 months of primary care training, whether educational deficiencies in obstetrics and gynecology will develop as a result of the mandate, and whether residency programs should be lengthened to encompass primary care. RESULTS: The response rate for the survey was 92.3% (251/272). University-affiliated, community, and military-based programs were surveyed and all geographic areas of the country were represented. Of program directors responding, 53.4% agreed with the mandate, 43.0% disagreed, and 3.6% declined to answer this question or both agreed and disagreed. Fifty-one percent considered 6 months of primary care training to be adequate, and 60.2% of program directors thought that educational deficiencies would develop in obstetrics and gynecology training programs. Whereas 66.1% responded that extension of obstetrics and gynecology training programs beyond 4 years was unnecessary, 32.7% thought program length should be increased. CONCLUSION: The results of this survey demonstrate that a substantial proportion of U.S. residency directors do not agree with the Residency Review Committee mandate for primary care training and think that deficiencies in obstetrics and gynecology training will develop as a result of these changes.

The effects of prolactin on human sperm capacitation and acrosome reaction.

OBJECTIVE: To study the effects of human prolactin (PRL) on human sperm capacitation and acrosome reaction. DESIGN: Acrosome reactions were induced by the addition of follicular fluid (FF) and progesterone (P). Experiments were performed to determine time and dose-dependent effects of PRL on sperm capacitation, potentiation of the acrosome reaction, decapacitating effects, and potential for PRL to induce an acrosome reaction. RESULTS: An average of 31.5% of spermatozoa underwent acrosome reaction with addition of FF and P. No time- or dose-dependent PRL effects on sperm capacitation or acrosome reaction were found (P greater than 0.05). CONCLUSION: Prolactin does not play an important role in human sperm capacitation or acrosome reaction.

Immunohistochemical detection of type I, III, and IV collagen in endometriosis implants.

OBJECTIVE: To determine if types I, III, or IV collagen are present in ectopic endometrium and to determine which type(s) of collagen are present in the connective tissue surrounding ectopic endometrial implants. DESIGN: Paired intrauterine and ectopic endometrial samples were obtained for study at the time of laparoscopy from women in the proliferative and secretory phase of the menstrual cycle. Connective tissue surrounding each ectopic implant was also obtained for study. SETTING: Academic research environment with institutional review board approval. PATIENTS: Six patients without endometriosis were used as controls. Ten additional patients with stage II or III endometriosis were studied. Only women on no medications participated in the study. MAIN OUTCOME MEASURES: Immunohistochemical techniques were used to identify the presence of collagen in biopsied specimens. RESULTS: Each collagen type studied was identified in the intrauterine endometrium of patients with and without endometriosis. All collagen types were also identified in each of the ectopic endometrial implants studied. The distribution of collagen in ectopic endometrial implants was similar to the distribution of collagen seen in intrauterine endometrium obtained from patients with or without endometriosis. Collagenous tissue that contained type I collagen was identified at the periphery of deep ectopic implants. CONCLUSIONS: This study demonstrates the presence of type I, III, and IV collagen in the intrauterine and ectopic endometrium of patients with endometriosis. Type I collagen was the predominant collagen present in the surrounding collagenous tissue associated with deep, ectopic endometrial implants.

The role of aerobic and anaerobic semen cultures in asymptomatic couples undergoing in vitro fertilization: effects on fertilization and pregnancy rates.

OBJECTIVE: To determine if routine semen culture is useful in asymptomatic couples undergoing in vitro fertilization and embryo transfer (IVF-ET). DESIGN: Prospective data collection. SETTING: All cultures and IVF cycles were performed at the University of North Carolina in Chapel Hill, North Carolina. PARTICIPANTS: All asymptomatic couples undergoing IVF-ET from January 1989 through January 1990. INTERVENTIONS: Aerobic and anaerobic cultures were performed on semen samples obtained before IVF. MAIN OUTCOME MEASURES: Quantitative semen cultures were evaluated for both aerobic and anaerobic bacterial isolates. Fertilization and pregnancy rates (PRs) were compared in patients with positive and negative semen cultures. RESULTS: Eighty percent of cultures contained at least one bacterial isolate. Three of the four most commonly isolated bacteria were normal skin flora. Positive culture results had no effect on either fertilization or PRs. CONCLUSIONS: Bacterial contamination is common with semen collection, yet routine semen cultures are not beneficial in asymptomatic couples undergoing IVF-ET.

Endometriosis-associated pelvic pain: evidence for an association between the stage of disease and a history of chronic pelvic pain.

OBJECTIVE: To track the severity and location of pelvic pain associated with endometriosis throughout the reproductive-age years and to evaluate the association between these pain parameters and the stage of disease. DESIGN: Historical prospective study. SETTING: Tertiary care center. PATIENT(S): Forty-eight women with endoscopically staged endometriosis and chronic pelvic pain who had undergone medical and/or conservative surgical therapy. INTERVENTION(S): Each participant was administered a questionnaire that included a determination of the severity and location of her pain. MAIN OUTCOME MEASURE(S): The stage of disease, the area of the pelvis that contained the bulk of disease, the severity of pain, and the location of the most severe pain were recorded. RESULT(S): The mean duration from the initial diagnosis until follow-up was 15.7 +/- 3.1 years, Twenty-one (43.8%) subjects denied any symptoms of pain on follow-up evaluation. Of the 27 patients with persistent pain, 21 (78%) identified the location of their most severe pain as being the same as at initial diagnosis. The stage of disease at initial diagnosis was significantly associated with a higher degree of pain at follow-up. CONCLUSION(S): These data suggest that endometriosis-associated chronic pelvic pain commonly persists throughout the reproductive years and that endometriosis stage is directly related to the persistence of pelvic pain.

Cost-effective treatment of the infertile couple.

OBJECTIVE: To review the published literature on the cost-effective approach to infertility treatment. DESIGN: The literature on the economics and cost-effectiveness of infertility treatments was reviewed. Studies related to this topic were identified through MEDLINE. RESULT(S): Few cost-effectiveness studies about infertility treatment have been published. In the absence of tubal blockage and severe male factor, use of IUI and hMG-IUI is more cost-effective than IVF. In vitro fertilization is at least as cost-effective as tubal surgery. Although IVF costs are high, they fall well within the range of other accepted medical treatments and are below the general public's willingness to pay for these treatments. CONCLUSION(S): Cost-effectiveness analysis is an important means of improving quality of care while controlling costs. Further work regarding cost-effectiveness of treatments among different diagnostic groups is needed.

Selective early elimination of luteal support in assisted reproduction cycles using a gonadotropin-releasing hormone agonist during ovarian stimulation.

OBJECTIVE: To determine if women undergoing GnRH agonist-hMG stimulated IVF cycles can undergo successful discontinuation of luteal phase support. DESIGN: A protocol for selective discontinuation of luteal phase support was evaluated prospectively in women undergoing assisted reproduction cycles. SETTING: A tertiary care institutional-based assisted reproduction program. PATIENT(S): One hundred eighty-eight women who conceived after an IVF or zygote intrafallopian transfer cycle including a GnRH agonist between January 1994 and June 1997. INTERVENTION(S): Women with serum progesterone levels of > or = 60 ng/mL at 4 weeks' gestation were selected for discontinuation of their luteal phase support. MAIN OUTCOME MEASURE(S): Delivery rate. RESULT(S): Sixty-three women (62.4%) met the criteria for discontinuation of luteal phase support. There were no differences in the mean age, peak E2 levels, number of follicles, number of embryos transferred, or delivery rates (85.7% versus 78.9%) between the women who did and those who did not have discontinuation of their progesterone supplementation. CONCLUSION(S): These data reveal that luteal phase support can be discontinued successfully for selective women undergoing IVF who are receiving a GnRH agonist.

Sperm recovery and survival: two tests that predict in vitro fertilization outcome.

OBJECTIVES: To determine if human sperm recovery during swim-up and sperm survival after 24 hours, as obtained from a screening semen specimen, are predictive of subsequent IVF and clinical pregnancy rates (PRs) and to determine if these techniques can identify men with normal semen analysis parameters and poor IVF success. DESIGN: Historical prospective study. SETTING: All semen evaluations and IVF cycles were performed at the University of Pittsburgh, Magee-Womens Hospital, Pittsburgh, Pennsylvania. PATIENTS, PARTICIPANTS: Couples undergoing IVF at Magee-Womens Hospital from August 1988 through June 1993. INTERVENTIONS: A screening semen analysis and swim-up procedure were performed on all couples undergoing IVF. The number of spermatozoa recovered after swim-up and the percentage of motile spermatozoa present after a 24-hour incubation were recorded. MAIN OUTCOME MEASURES: Fertilization and PRs were compared according to the parameters obtained from routine semen analysis, the number of spermatozoa obtained with swim-up, and the percentage of motile spermatozoa at 24 hours. RESULTS: Using chi2 or Fisher's exact test, fertilization rates were significantly different according to the number of spermatozoa recovered after swim-up (< or = 2.0 and > 2.0 x 10(6) spermatozoa recovered, 48.3% versus 71.4%) as were PRs (16.9% versus 29.8%). Similarly, the percentage of motile spermatozoa present at 24 hours (< or = 20% and > 20%) discriminated between fertilization rates (45.9% versus 65.8%) and PRs (16.4% versus 36.5%). Among a subset of men with normal semen analyses and total motile sperm counts > or = 40 x 10(6), the results from swim-up and survival discriminated between men with high and low fertilization and PRs. Receiver operating characteristic analysis revealed that swim-up results better discriminated between pregnant and nonpregnant IVF patients than sperm motility, but that the percentage of motile spermatozoa present at 24 hours was no better in this regard than sperm motility. CONCLUSIONS: The number of spermatozoa recovered after swim-up and the percentage of spermatozoa that maintain their motility after 24 hours were both helpful in assessing IVF and PRs and may be helpful in altering physicians to a subset of men having normal semen analysis parameters yet poor IVF success.

The efficacy and cost effectiveness of embryo cryopreservation compared with other assisted reproductive techniques.

OBJECTIVE: To evaluate the efficacy and cost effectiveness of embryo cryopreservation compared with other assisted reproductive techniques (ARTs). DESIGN: Retrospective review of medical records and health care costs. SETTING: Tertiary care academic medical school ART program. PATIENTS: For determination of the efficacy of cryopreserved ET, we analyzed 610 patients undergoing the first 1,000 oocyte retrievals in our program. For determination of cost effectiveness, we analyzed the costs associated with 334 initiated ART cycles in 1992. MAIN OUTCOME MEASURES: The ongoing pregnancy rate (PR) per initiated cycle and per oocyte retrieval. The medical costs associated with each procedure. RESULTS: The transfer of cryopreserved embryos increased the ongoing PR per oocyte retrieval by 6.6%. Transfer of cryopreserved embryos was cost effective compared with other ARTs. The cost per delivery for cryopreserved ETs was between 25% and 45% that of a fresh cycle. CONCLUSIONS: Including embryo cryopreservation in an ART program can improve PRs and lower the ultimate cost per delivery.

Cost-effectiveness of infertility treatments: a cohort study.

OBJECTIVE: To determine the cost-effectiveness of infertility treatments. DESIGN: Retrospective cohort study. SETTING: Academic medical center infertility practice. PATIENT(S): All patients treated for infertility in a 1-year time span. INTERVENTION(S): Intrauterine inseminations, clomiphene citrate and IUI (CC-IUI), hMG and IUI (hMG-IUI), assisted reproductive techniques (ART), and neosalpingostomy by laparotomy. MAIN OUTCOME MEASURE(S): All medical charges and pregnancy outcomes associated with the treatments were obtained. Cost-effectiveness ratios defined as cost per delivery were determined for each procedure. The effects of a woman's age and the number of spermatozoa inseminated on cost-effectiveness of the procedures was also determined. RESULT(S): Intrauterine inseminations, CC-IUI, and hMG-IUI have a similar cost per delivery of between $7,800 and $10,300. All of these were more cost-effective than ART, which had a cost per delivery of $37,000. Assisted reproductive techniques in women with blocked fallopian tubes was more cost-effective than tubal surgery performed by laparotomy, which had a cost per delivery of $76,000. Increasing age in women and lower numbers of spermatozoa inseminated were factors leading to higher costs per delivery for IUI, CC-IUI, hMG-IUI, and ART. Use of donor oocytes reduced the cost per delivery of older women to the range seen in younger women with ART. CONCLUSION(S): Our analysis supports, in general, the use of IUI, CC-IUI, and hMG-IUI before ART in women with open fallopian tubes. For women with blocked fallopian tubes, IVF-ET appears to be the best treatment from a cost-effectiveness standpoint.

Endometriosis impairs the efficacy of gamete intrafallopian transfer: results of a case-control study.

OBJECTIVE: To determine whether pelvic endometriosis impairs the efficacy of GIFT. DESIGN: Matched follow-up study. SETTING: University-based assisted reproduction program. PARTICIPANTS: Patients undergoing GIFT between 1987 and 1991. Cases had a primary diagnosis of endometriosis. Controls had no endometriosis and were matched with cases according to age, number of mature eggs transferred, and sperm grade. INTERVENTION: Gamete intrafallopian transfer was performed in all patients in an identical manner independent of their underlying diagnosis. MAIN OUTCOME MEASURES: Pregnancy and delivery rates. RESULTS: Of 114 laparoscopic egg retrievals performed in the endometriosis group, there were 37 pregnancies (32.5%) and 27 deliveries (23.7%). Of the 214 retrievals in the control group, there were 101 pregnancies (47.2%) and 76 deliveries (35.5%). Mantel-Haenszel estimates of relative risk indicated that endometriosis significantly impaired pregnancy and delivery rates. There was no statistically significant difference in pregnancy rates according to severity of disease among endometriosis cases. There was no statistically significant difference in pregnancy rates according to severity of disease among endometriosis cases. CONCLUSIONS: Our finding that GIFT pregnancy rates were lower in women with a primary diagnosis of endometriosis than in matched controls suggests that endometriosis is associated with reduced efficacy of GIFT.