Carolyn B. Coulam

incidence of Premature Ovarian Failure

To assess the occurrence of premature ovarian failure, the age-specific incidence rates of natural menopause were determined for a cohort of 1858 women born between 1928 and 1932. These women were identified as Rochester, Minnesota residents in 1950 and were followed for date and type of menopause. A total of nine experienced natural menopause before age 40 years, which represents a 1% risk of natural menopause to age 40. The annual incidence rates of natural menopause per 100,000 person-years were ten for ages 15 to 29 and 76 for ages 30 to 39. In the age group 40 to 44, the incidence of natural menopause increased greatly to 881 per 100,000 person-years at risk.

Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women

To test the widely accepted--but not well-supported--impression that endometriosis and infertility are associated, we compared the prevalence of endometriosis visualized at laparoscopy in 100 patients being evaluated for infertility and in 200 fertile control subjects (two age-matched to each patient) undergoing tubal ligation. The extent of endometriosis and adhesions noted in the operative reports was classified according to the system proposed by The American Fertility Society. Endometriosis was found in 21 of the 100 infertile patients--mild in 11, moderate in 8, severe in 2. It was found in 4 (2%) of the 200 controls and was mild in all 4. Thus, endometriosis is more often present, and more often severe, among infertile patients. The risk of infertility was estimated to be almost 20 times greater with endometriosis than without. These data support the clinical impression that an association exists.

Ultrasonographic predictors of implantation after assisted reproduction

OBJECTIVE To assess the utility of endometrial thickness, echogenic endometrial pattern, and uterine artery impedance measured as pulsativity index in predicting implantation. DESIGN Prospective case-controlled study of infertile patients undergoing assisted reproductive technologies (ARTs). PATIENTS Four hundred five women undergoing ARTs were studied: 100 women after ET of thawed embryos in natural cycles (frozen ET), 107 women after standardized IVF-ET, 99 women receiving donor oocytes after controlled endometrial development with estrogen and P, and 99 women undergoing IUI with various ovarian stimulation regimens (none, 16; GnRH, 7; clomiphene citrate [CC], 29; hMG, 47). INTERVENTIONS Transvaginal ultrasonographic examination performed on the day of hCG administration during stimulated cycles; on E2 day 15 during controlled endometrial cycles; and on the day of ovulation during natural, CC, and GnRH pump cycles. MAIN OUTCOME MEASURE The endometrial thickness, echogenic pattern, and pulsativity index results in 170 conception cycles were compared with 235 nonconception cycles. RESULTS When conception and nonconception cycles were compared, no difference in mean endometrial thickness and significant differences in the frequency of nonmultilayered pattern and pulsativity index > 3.3 were observed. Forty-seven percent of nonconception and 9% of conception cycles were associated with at least one of these factors. CONCLUSION Ultrasonic measurements of pulsativity index, resistance index, and echogenic pattern are useful in predicting implantation after assisted reproduction.

Systemic CD56+ Cells Can Predict Pregnancy Outcome

PROBLEM: To evaluate differences in circulating CD56+ cells between successful and unsuccessful pregnancies, 114 pregnant women were studied prospectively.

Epidemiology of Recurrent Spontaneous Abortion

ABSTRACT: With recent scientific advances leading to better understanding of the immunobiology of recurrent spontaneous abortion (RSA), interest has now focused upon the epidemiology of RSA. A cohort of 214 couples with a history of two or more consecutive abortions were studied for the prevalence of etiologic factors and association with other reproductive failures. The prevalence of causes of RSA in this cohort was compared with etiologic factors among 179 couples with a history of three or more consecutive abortions. The obstetrical histories of 214 women with RSA were analyzed for the total number of pregnancies, live births, stillbirths, spontaneous abortions, ectopic pregnancies, and hydatidiform moles. These numbers were compared with the expected frequency of each in the general population. The prevalence of etiologies among 214 with RSA were as follows: chromosomal—6%, anatomic—1%, hormonal—5%, immunologic—65%, and unexplained—23%. No differences in the prevalence of etiologic factors exist when couples with a history of two or more abortions are compared with three or more abortions. When the number of ectopic pregnancies, molar pregnancies, and stillbirths among 214 women with RSA were compared with the expected numbers, the odds ratios were 2.2 for ectopic pregnancies, 6.0 for molar pregnancies, and 2.3 for stillbirths. These data indicate that no difference in the prevalence of etiologies of RSA exist when couples with two or more abortions are compared with three or more and a comorbidity between RSA and other types of reproductive failure exists.

Multiple Thrombophilic Gene Mutations Rather than Specific Gene Mutations are Risk Factors for Recurrent Miscarriage

Recurrent miscarriage is a heterogeneous condition. While the role of acquired thrombophilia has been accepted as an etiology of recurrent miscarriage, the contribution of specific inherited thrombophilic genes to this disorder has remained controversial. We compared the prevalence of 10 thrombophilic gene mutations among women with a history of recurrent miscarriages and fertile control women.

Do Anticonvulsants Reduce the Efficacy of Oral Contraceptives

Summary: Women in our area with epilepsy who were also taking oral contraceptives were identified. Of 82 patients taking oral contraceptives, 41 had used both anticonvulsants and oral contraceptives for a total of 955 months. Three documented oral contraceptive (pill) failures occurred during this period, whereas the expected number was 0.12 (relative risk, 25; 95% confidence interval, 5 to 73). No pill failures were observed in 2,278 months among women with epilepsy who were taking oral contraceptives but who were not taking anticonvulsants at this time. Thus our data support the suggestion that there is an increased rate of pill failure among women taking anticonvulsants. In view of this diminished effectiveness, the advisability of using oral contraceptives rather than one of the other forms of contraception when anticonvulsant medication is being used concurrently may need to be reevaluated.

Laboratory Evaluation of Women Experiencing Reproductive Failure

Reproductive life table analysis indicates that the majority of reproductive failures result from post fertilization failures, whether before or after implantation. It is important to have a set of tests to clarify the diagnosis of the reproductive failure so that appropriate therapy can be instituted. To determine the frequency of abnormal immunologic tests among women experiencing reproductive failure, 108 patients were evaluated for the presence of antiphospholipid antibodies (APA); lupus anticoagulant (LA); thyroid‐thyroglobulin and microsomal antibodies (TGT); embryotoxic factor (ETA); and systemic CD56+/CD16‐ cells. The frequency of abnormal results obtained from testing for APA, LA, TGT, ETA, and CD56+/CD16‐ cells among 108 patients with diagnoses of recurrent pregnancy loss (RPL)(n=45), unexplained infertility (n=45) including IVF failure (n=10), endometriosis (n=10), premature ovarian failure (n=5), and polycystic ovaries (n=3) were compared with 15 normal controls. Seventy of one hundred eight (65%) women experiencing reproductive failure had at least one positive test, compared to 1 of 15 (7%) controls (P=0.0001). Presence of phospholipid antibodies was the most frequently abnormal result followed by elevated CD56+/CD16 cells. The prevalence of a particular abnormal test varied among the diagnoses. The most frequent abnormal test among women with RPL was an increased percentage of CD56+/CD16‐ cells (40%), followed by APAs (29%), TGT (9%), and ETA (7%). The most frequent abnormal result among women with unexplained infertility was the presence of APAs (42%), followed by CD56+/CD16‐ cells (16%), ETA (16%), and TGT (9%). APA, CD56+/CD16‐ cells, ETA, and TGT are useful tools to assist in the diagnosis of reproductive failure.

Total and free testosterone during pregnancy

Total and free testosterone levels were measured throughout pregnancy and were compared with values found in nonpregnant women to determine whether the increase in plasma testosterone levels during pregnancy can be accounted for entirely by an increase in sex hormone-binding globulin or by an increase in testosterone production that would be reflected by an elevation in plasma free testosterone. The study employed a practical and precise method of determining free testosterone by means of equilibrium dialysis. Even though the testosterone level increased significantly throughout pregnancy, the free testosterone level remained within the range for nonpregnant women until week 28, after which time it was significantly elevated. This indicates that the increase in the total testosterone level before week 28 is due to a decrease in metabolic clearance rate, but after week 28 the production rate is increased. The source of this increase is unknown, but it might be fetal.

Multiple thrombophilic gene mutations are risk factors for implantation failure

While the role of inherited thrombophilia has been accepted as a cause of recurrent late pregnancy complications, the contribution of mutated thrombophilic genes to implantation failure has not been studied. Proteins involved in fibrinolysis are necessary for trophoblast invasion into the endometrium. This study compared the prevalence of 10 thrombophilic gene mutations among 42 women with a history of recurrent implantation failure after IVF–embryo transfer with 20 fertile control women. Buccal swabs were taken from all of the women for DNA analyses. Women with a history of implantation failure after IVF–embryo transfer displayed a higher prevalence of PAI-1 4G/5G mutations than controls (P = 0.007). No differences in the frequency of the other specific gene mutations were detected. However, the prevalence of total gene mutations among patients with implantation failure was significantly higher than among controls. More than three gene mutations among the 10 genes studied were observed in 74% of women with implantation failure and 20% of controls (P = 0.0004). It is concluded that inherited thrombophilias are associated with implantation failure. This association is manifest by total number of mutations as well as with PAI-1 mutations.