CA 125 levels measured in different phases of the menstrual cycle in screening for endometriosis.

OBJECTIVE: To examine variations in CA 125 levels during the three phases of the menstrual cycle in women with and without endometriosis. METHODS: One hundred infertile women were studied prospectively. CA 125 levels were measured during menses and during the follicular and luteal phases before diagnostic laparoscopy. Subjects were divided into four groups: no evidence of endometriosis (35 women), stage I endometriosis (30 women), stage II endometriosis (21 women), and stages III and IV endometriosis (14 women). RESULTS: In the endometriosis groups, there was a significant difference in the mean CA 125 levels drawn at menses and those drawn in the follicular phase. In patients with severe endometriosis, there was also a difference in the mean CA 125 levels drawn at menses and in the luteal phase. This finding led to the development of a screening test based on the ratio of CA 125 levels at menses to levels in the follicular phase. The test based on this ratio (with a cutoff of 1.5) had a sensitivity of 62.5% and specificity of 75%, compared with a sensitivity of 26.8% and specificity of 100% for the test based on a single CA 125 level drawn at menses (with a cutoff of 35 U/mL). CONCLUSIONS: CA 125 levels during menses are elevated compared with those during the follicular phase in patients with endometriosis. Screening tests based on the relationship of multiple CA 125 levels taken throughout the menstrual cycle were more sensitive for detection of endometriosis than tests based on a single CA 125 level.

Serum CA 125 levels in early pregnancy and subsequent spontaneous abortion.

CA 125 has been found in high concentrations in human amniotic fluid throughout gestation, with significant quantities seen in the decidua and chorion. Because disruption of the epithelial basement membrane of the fetal membrane or the decidua could theoretically lead to a rise in maternal CA 125 levels, this increase may be a predictor of subsequent spontaneous abortion of the fetus. A study was initiated to investigate whether a sudden rise in the serum CA 125 level might predict spontaneous first-trimester abortions. CA 125 levels of 101 pregnant women were evaluated 18-22 days from conception and 6 weeks from conception (a frequent time for spontaneous abortion) to determine whether there is a sudden increase (from baseline or early trimester levels) during the middle or late first trimester immediately before or at the time of abortion. The results indicated that although there was a definite correlation found between elevation of CA 125 and spontaneous abortion, the higher levels occurred early in the first trimester whereas the majority of abortions did not occur until much later, after fetal viability was established. Six of ten women with CA 125 levels of 150 U/mL or greater aborted, compared with four of 92 women with CA 125 levels less than 150 U/mL. One of 11 women pregnant after in vitro fertilization had a CA 125 level above 150 U/mL, and she aborted.

Successful delivery after age 50: a report of two cases as a result of oocyte donation.

BACKGROUND: Because of donor oocyte programs, women who previously were considered too old to successfully achieve conception and delivery can now bear children. To our knowledge, there have been no previous reports of pregnancy outcome in women over age 50 who conceived using donor oocytes. This study presents the pregnancy and delivery data on two women who delivered at age 52. CASES: Case 1 was a 51-year-old woman, gravida 3, para 3, whose three children had been conceived with her first husband more than 20 years previously. She had remarried 18 years before presentation and had been actively trying to conceive for the last 7 years. She was diagnosed as being in menopause based on elevated gonadotropins, amenorrhea, and failure to have progesterone-withdrawal menses. She conceived on her first embryo transfer cycle with embryos derived from donor oocytes and fertilized by her husband's sperm (oocytes were donated by a woman who was undergoing retrieval for in vitro fertilization). During pregnancy she remained healthy, but had uterine prolapse at 20 weeks. She delivered a normal healthy male at 40.5 weeks; cesarean was performed because of a presumptive diagnosis of fetal distress after 3 hours of labor, when monitoring revealed fetal heart decelerations. Case 2 was also a 51-year-old woman, gravida 6, para 4, who wished to conceive with her second husband's sperm through the donor oocyte program. She had amenorrhea of 2 years' duration and elevated gonadotropins. Conception occurred after fertilization of a donor oocyte by her husband's sperm. She had an uneventful pregnancy, but labor was induced at 38 weeks' gestation given the supposed high-risk status of this age group. Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. CONCLUSION: Theoretically, the risks of pregnancy complications in older patients are magnified given the aging maternal cardiovascular system, which may predispose these women to placental insufficiency. These first two cases of donor oocyte pregnancies in women over age 50 found no maternal or fetal age-related complications. We hope these reports will encourage all researchers to share their findings so that prospective patients can make better, more informed decisions as to whether they want to participate in donor oocyte programs.

Influence of endometrial thickness and echo patterns on pregnancy rates during in vitro fertilization.

Previous data has suggested that improved PRs were seen in women with increased endometrial thickness as determined by sonography before oocyte retrieval. The hyperstimulation protocol used was CC-hMG. The study presented herein was initiated to evaluate if a similar trend was evident in women whose hyperstimulation protocol included the long LA-hMG therapy. We also demonstrated an improved PR in women with greater endometrial thickness, but in general, the endometrium was thicker in the pregnant women treated with the gonadotropin-releasing hormone agonist than in those treated with CC.

The effect of endometrial thickness and echo pattern on in vitro fertilization outcome in donor oocyte-embryo transfer cycle.

There have been some conflicting data concerning the importance of endometrial thickness and echo patterns before transfer in different IVF-ET situations under different COH regimens. We previously found in women undergoing IVF-ET after luteal phase LA-hMG a significantly higher PR in those patients attaining at least a 10-mm endometrial thickness and a lower rate in those women with an entirely homogeneous hyperechogenic endometrium (pattern C). The present study evaluated the relationship of endometrial thickness and echo pattern to PRs in donor oocyte recipient immediately before transfer. There were 16 pregnancies in 58 cycles (27.5%). Conclusions similar to the previous COH study were reached concerning the > or = 10-mm thickness levels correlating with improved PRs (9% versus 38.7%, P < 0.01). In contrast, no correlation with echo pattern was found.

Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea.

The efficacy of a technique of gonadotropin suppression and human menopausal gonadotropins (hMG) to induce ovulation in women with hypergonadotropic amenorrhea was evaluated in 100 consecutive women. Ovulation was achieved in 19% of cycles (68/361), the pregnancy rate per cycle was 5.2% (19/361), and the viable pregnancy rate was 2.2% (8/361). In the majority of the successful cases, estrogen was used to decrease the elevated luteinizing hormone and follicle-stimulating hormone levels, especially where the ethinyl estradiol therapy alone induced a rise in endogenous 17 beta-estradiol levels with hMG used to boost the follicle to maturation. Although the success rate is low, this technique can result in some successes in otherwise almost hopeless cases.

The hypoosmotic swelling test as a useful adjunct to the semen analysis to predict fertility potential.

The sperm HOS test was highly predictive of eventual achievement of pregnancy in women in whom other infertility factors had been corrected. No woman conceived whose partner's HOS was less than 50%. The results of spermiograms did not correlate with conception rate.

Viable pregnancy in a woman with premature ovarian failure treated with gonadotropin suppression and human menopausal gonadotropin stimulation. A case report.

Ovulation and pregnancy were achieved in a woman with premature ovarian failure by mildly suppressing the elevated gonadotropins and following with a small dose of human menopausal gonadotropins for completion of follicular maturation.

Clinical evaluation of the Pipelle endometrial suction curette for timed endometrial biopsies.

A clinical study was performed to determine the efficacy of the Pipelle in obtaining endometrial samples to be analyzed for luteal function. Patients' tolerance of this instrument and their willingness to undergo subsequent biopsies were also ascertained. An endometrial sample was obtainable from 1,278 women with the Pipelle, whereas 52 required the Novak curette and in 60 the sample could not be obtained with either instrument. Thirteen percent of the patients biopsied with the Pipelle stated that they would not allow a second such procedure to be performed. One percent of the samples were deemed inadequate for hormonal reading. The Pipelle seemed to be a safe, minimally traumatic method of sampling the endometrium for hormonal evaluation.

Successful delivery of twins in a woman with a unicornuate uterus.

The presence of a unicornuate uterus is a rare congenital condition which represents only 1-2% of uterovaginal anomalies. Previous reports have demonstrated an increase in the number of cases of primary infertility, pregnancy loss and preterm labor associated with the unicornuate uterus. Herein, we present a case in which a patient conceived following a thawed frozen embryo transfer. She had been given the option of selective reduction, because of the high risk associated with this pregnancy, but refused and her pregnancy successfully continued to 35 weeks and delivery of twins.

Extreme elevation of serum CA-125 in two women with severe endometriosis: case report.

Two women with elevated preoperative serum CA-125 levels were found to have extensive endometriosis - one, the highest level related to endometriosis ever reported in the English literature. Endometriosis was found to be etiologic as seen by the prompt reduction in serum CA-125 levels following surgical treatment limited to endometriosis. Thus, a very high CA-125 level does not necessarily forebode ovarian malignancy.

Comparison of short versus long-term leuprolide acetate--human menopausal gonadotrophin hyperstimulation in in-vitro fertilization patients.

The use of leuprolide acetate for at least 10 days beginning in the mid-luteal phase prior to initiating human menopausal gonadotrophin (HMG) stimulation has been fairly successful in preventing cancellations for premature luteinization and allowing retrieval of more oocytes, which in turn provide more embryos for cryopreservation. However, it is theoretically possible that the long-term use of leuprolide may have some adverse effect on either pregnancy rates or on mean survival after cryopreservation and thawing. Recently, a short 3 day regimen of a gonadotrophin-releasing hormone agonist, buserelin effectively prevented premature luteinization during HMG stimulation. The present study indicated that substitution of a 3 day course of leuprolide acetate also effectively prevented premature luteinization but was less expensive, required statistically fewer ampoules of HMG and much less leuprolide.

An in vivo technique for screening immunologic factors in the etiology of the unexplained poor postcoital test.

A study was designed to determine the incidence and etiology of the unexplained poor postcoital test. An in vivo comparison of sperm penetration by husband's versus donor sperm in the wife's estrogen-stimulated mucus was performed. The 8 of 30 women showing improvement of husband's penetration in mucus (group 1) were treated with high-dose estrogen (HDE) and hMG, and 4/8 conceived. Anti-sperm antibodies (ASA) were insignificant in this group. In group 2, in which donor sperm penetrated but husband's sperm did not, 8 men of 17 were found to have an ASA level over 50% on the sperm surface; 6/8 treated with high-dose methylprednisolone (MP) had an improved postcoital test, and 5 achieved a pregnancy. Two patients with levels under 50% were still treated with MP, and one achieved a pregnancy. In five group-3 couples, positive ASA were found in the cervical mucus of two women; and one woman improved on the postcoital test and conceived following MP therapy. The 30 unexplained poor postcoital tests occurred in 5,000 couples evaluated. In general, those patients considered to have significant clinical antibody had levels over 50%. Because side effects of MP may be severe, and positive ASA may be found in normal donors, it is important to use a comparison penetration test to help determine if treatment with corticosteroids seems reasonable.

Comparison of various therapies for the luteinized unruptured follicle syndrome.

A study was initiated to evaluate the prevalence of the luteinized unruptured follicle (LUF) syndrome in a group of 355 women with infertility. The diagnosis was established by carefully observing daily sonograms along with measuring estradiol, progesterone, and luteinizing hormone (LH) levels. Two distinct types of LUF syndrome were identified: mature follicle LUF, in which release of an ovum was not demonstrated after a follicle attained maturity (serum estradiol reached 200 pg/mL while serum progesterone remained less than 2.5 ng/mL), versus premature luteinization LUF, where the serum progesterone increased above 2.5 ng/mL before follicular maturation was attained. The use of either hCG alone or hCG in combination with hMG in a single injection at the time of follicular maturation successfully corrected mature follicle LUF in 21 of 46 patients (46%), whereas ovulation-inducing drugs plus hCG or hCG and hMG corrected LUF in 24 of 25 patients (96%). Clomiphene citrate proved inferior to hMG in that it corrected LUF in 3 of 25 patients (12%) versus 12 of 22 patients (95%) who had undergone hMG therapy. Thus, hMG-hCG therapy is the most efficacious for mature follicle LUF, but because release can occur spontaneously on occasion by an appropriately timed single gonadotropin injection, one could offer the less costly options first. For premature luteinization, speeding up follicular maturation with gonadotropin therapy is effective. Upon failure of this technique, the more costly endogenous gonadotropin suppression followed by hMG can be employed.

Evidence that difference in size of fraternal twins may originate during early gestation: a case report.

We describe a woman who conceived by in vitro fertilization (IVF) and embryo transfer (ET). Transvaginal ultrasound demonstrated at least 1 week's difference in size of twin gestations from 1 month post-transfer of embryos to delivery. Differences in sac size, crown-rump length, and gestational growth are discussed, as are implications of ultrasound in early pregnancy.

An evaluation of couples with failure of fertilization in vitro.

Attempts at in-vitro fertilization (IVF) may be used as a method of evaluating whether in a given couple, the inability of the sperm to fertilize the oocyte may be the cause of infertility. We evaluated all IVF patients in our practice who had at least one cycle with no fertilization to determine how often this was an isolated event or was repeated in multiple cycles; would poor semen quality be found as a frequent cause; and how well can a donor sperm or oocyte 'probe' uncover which of the two is the problem? Of 35 couples who used their own gametes exclusively, 30 (85.7%) had at least one cycle with zero fertilization; 42.5% of those failing to fertilize in cycle 1 and 35% of those failing in cycle 2 had a subnormal concentration of motile spermatozoa, morphology or hypo-osmotic swelling test scores. The pregnancy rate per cycle with both husband's and wife's gametes was only 2.3% (3/130), but was 8.3% for those using donor spermatozoa (3/36) and 18.2% (2/11) for donor oocytes. Thus, failing to fertilize in a given cycle does not necessarily predict failure to fertilize in a subsequent cycle, but does predict a poor fertility outcome unless donor gametes are used.

Serum progesterone and 17-hydroxyprogesterone in the diagnosis of ectopic pregnancies and the value of progesterone replacement in intrauterine pregnancies when serum progesterone levels are low.

The corpus luteum function was evaluated in patients with surgically confirmed ectopic pregnancy (EP) in a multicenter study. In addition, the minimal threshold of serum progesterone (P) concentration required for salvaging intrauterine pregnancies (IUP) was also examined. Results show that single P or 17-OHP measurements are not diagnostic for EP, since mean P levels in EP were similar to those with spontaneous abortion though significantly lower than those in controls. 17-OHP levels in EP overlapped in 50% with IUP, and the mean levels were significantly lower only at 6-7 weeks. The 17-OHP levels when compared to hCG supports the view that corpus luteum defect is primary. In IUP, P levels < 8 ng/ml still were associated with viable (60%) pregnancy; thus no minimal threshold could be established.

Comparison of pregnancy rates following in vitro fertilization-embryo transfer between the donors and the recipients in a donor oocyte program.

Our in vitro fertilization (IVF) program provides a unique opportunity to evaluate influences of hormonal milieu on pregnancy outcome, by using a shared pool of oocytes obtained by donors (in exchange for financial assistance). The study presented herein evaluated 38 retrieval cycles (28 oocyte donors/22 recipients). No difference in mean number of embryos transferred was seen (2.7 in the donors vs 2.8 in the recipients). However, a statistically significant difference was seen in the pregnancy rates per retrieval (10.5% donors vs 29% recipients) and per transfer (4/35, 11.1%, vs 11/34, 32.3%). Abortion rates were similar (25% donor, 27.2% recipients). These data suggest that other reports of higher pregnancy rates from donor oocyte programs may not be due exclusively to better-quality oocytes. Possibly a negative effect of hyperstimulation or adverse endometrial environment of the donor (possible chronic endometritis) may explain these data.

Correlation of serum progestagen-associated endometrial protein levels with endometrial biopsies serum steroid levels and therapy for luteal phase defects.

The progestagen-associated endometrial protein (PEP) level rises from the early to the late luteal phase. A study was performed in infertile women where late luteal phase endometrial biopsies and serum PEP levels were obtained. The objective of the study was to evaluate the correlation between the PEP levels and the endometrial biopsies and to determine if subnormal PEP levels could be improved by the same therapies used to correct endometrial defects. There was a poor correlation between PEP levels and endometrial biopsies (r = 0.17). Similarly, there was no significant correlation between PEP levels and levels of the following hormones: mid- and late-luteal phase progesterone (P) (r = 0.186 and 0.282 respectively), mid-luteal phase 17-hydroxyprogesterone (17-OHP) (r = 0.139) and mid-luteal phase oestradiol (r = 0.135). Furthermore, there was no correlation between PEP levels and the dosage of progesterone used in therapy (r = 0.07). There were no statistically significant differences in PEP values (U/ml) depending on whether any fertility drug was taken. Thus our data suggest that progesterone may only have a permissive role, with some other factor(s) controlling the actual rise and fall of PEP.