Evaluation of serum CA 125 concentrations as predictors of pregnancy with human in vitro fertilization.

OBJECTIVE: To determine if CA 125, a product of human endometrium, may be an indicator of early endometrial function. To test this hypothesis we examined CA 125 concentrations before oocyte retrieval in IVF cycles. DESIGN: Retrospective data analysis of 111 consecutive IVF cycles. SETTING: Tertiary care academic medical center. PATIENTS: All women who received luteal leuprolide acetate (LA) suppression followed by hMG for IVF and had sera available for analyses were entered into the study. MAIN OUTCOME MEASURE: Serum CA 125 was measured in the previous luteal cycle, day 7 of hMG, day before, and day of hCG administration. Twelve other variables were analyzed. RESULTS: Fifty-six cycles (47 women) qualified for evaluation and included 25 pregnant cycles (45%) and 31 nonpregnant cycles. Higher serum CA 125 concentrations were associated with pregnancy in both endometriosis and nonendometriosis subgroups. CA 125 values on the day of hCG administration were the best predictors of pregnancy, with levels > or = 16 U/mL having a sensitivity of 72%, specificity of 97%, and a positive predictive value of 95% for pregnancy. The other variables were not predictive of pregnancy. CONCLUSIONS: With a LA and hMG stimulation protocol, increased CA 125 concentrations before retrieval are associated with very high pregnancy rates. The source(s) of the serum CA 125, although as yet undertermined, may be of endometrial origin. The study supports further evaluation of CA 125 concentrations in IVF as a preretrieval predictor of pregnancy.

Serum from women with polycystic ovary syndrome inhibits fertilization and embryonic development in the murine in vitro fertilization model.

OBJECTIVE: To study the effects of serum collected from women with polycystic ovary syndrome (PCOS) on the fertilization and early embryonic development of the murine oocyte. DESIGN: Sera from women with anovulation were used as a supplement in a murine IVF model. SETTING: Tertiary care academic medical center. PATIENTS: Four fertile, four hypothalamic amenorrheic, seven PCOS (three with elevated LH and four with elevated T), and three anovulatory women with normal hormone levels. RESULTS: When compared with serum from fertile women, serum from women with PCOS reduced fertilization rates (60% versus 42%) and subsequent early embryonic development rates (87% versus 31%). Serum from women with PCOS and elevated T levels had the lowest fertilization rates (22%). Polycystic ovary syndrome serum with elevated T or LH levels significantly decreased early embryonic development rates in comparison to fertile women (22%, 41% versus 87%). CONCLUSIONS: Serum from women with PCOS inhibited fertilization and blastocyst development. Because both T and LH caused inhibited blastocyst development, these data have implications regarding low pregnancy rates and live birth rates during ovulation induction in women with anovulation. These data also raise questions regarding the use of serum during IVF.

Diagnosis and treatment of cornual obstruction using a flexible tip guidewire.

Proximal tubal obstruction, either unilateral or bilateral, is a frequent finding on hysterosalpingogram (HSG). Approximately two-thirds of the fallopian tubes resected for proximal tubal obstruction reveal an absence of luminal occlusion. The distinction between true pathologic occlusion and either spasm or plugging is crucial in determining therapy. We combined hysteroscopic cannulation of the proximal fallopian tube with laparoscopy in 11 patients with proximal tubal obstruction diagnosed by HSG and confirmed at laparoscopy. Hysteroscopic cannulation was able to be performed in 72% of the fallopian tubes attempted, and there was a postcannulation patency rate by HSG of 73%. Six of the 11 patients became pregnant after tubal cannulation and adjunctive distal tubal surgery. Hysteroscopic cannulation of the fallopian tube is a safe diagnostic procedure that can be used to identify those patients with true proximal occlusion, and may also serve as a therapeutic procedure in some of these patients.

The effect of serum from infertile women with endometriosis on fertilization and early embryonic development in a murine in vitro fertilization model.

OBJECTIVE: To evaluate the effect of serum from infertile women with endometriosis on fertilization and embryonic development in a murine IVF model. DESIGN: Pretreatment and post-treatment comparison of murine oocyte fertilization and early embryonic development with the addition of serum supplements from infertile women with endometriosis. SETTING: Tertiary care academic medical center. PATIENTS: Sera from 10 fertile women without endometriosis and 28 infertile women with endometriosis both before and after laser laparoscopy. RESULTS: When compared with serum from fertile women, serum from infertile women with endometriosis inhibited fertilization rates (51% versus 81%) and subsequent embryonic development rates (46% versus 79%). The inhibitory effect was greater as the stage of endometriosis increased. Treatment of endometriosis by laser laparoscopy improved both fertilization (51% versus 56%) and early embryonic development rates (46% versus 58%). CONCLUSIONS: Serum from infertile women with endometriosis inhibits both fertilization and early embryonic development in the murine IVF model. Inhibition of fertilization and early embryonic development rates increases as the stage of endometriosis increases. Improved fertilization and early embryonic development rates are observed after treatment of endometriosis by laser laparoscopy.

Clomiphene citrate ovulation induction in combination with a timed intrauterine insemination: the value of urinary luteinizing hormone versus human chorionic gonadotropin timing.

OBJECTIVE: To evaluate the clinical pregnancy rates (PRs) in anovulatory, male factor, and unexplained infertility using clomiphene citrate (CC) with an IUI and to evaluate the difference in PRs between urinary LH testing and hCG administration for timing of the IUI. DESIGN: Retrospective clinical study. SETTING: Academic, tertiary care fertility center. PATIENT(S): One hundred thirty-eight couples (432 cycles) undergoing IUI with CC ovulation induction as a treatment for unexplained, anovulatory, or male factor infertility were selected. INTERVENTION(S): All women with unexplained or male factor infertility received CC at a dose of 50 mg/d, and those with anovulation received CC at a dose ranging from 50 to 200 mg/d. All women in the study received a single IUI either the morning after a urinary LH surge or 36 to 38 hours after an evening hCG injection. MAIN OUTCOME MEASURE(S): Clinical PR. RESULT(S): There were no differences in the clinical PRs between LH testing or hCG administration in any of the three groups. Clinical PRs were extremely low in the male factor infertility group regardless of the timing used. CONCLUSION(S): These data suggest that the success of IUI with CC is not dependent on the method used to establish the timing for the IUI. In couples undergoing IUI with CC, the use of urinary LH testing may result in lower costs by reducing patient visits and the midcycle ultrasound.

Endometrial histology after first trimester spontaneous abortion.

The endometrial histology after spontaneous abortion was investigated by performing an endometrial biopsy in the two menstrual cycles subsequent to miscarriage in 12 women. In the first cycle, 66% (8/12) of the biopsies had the following abnormalities: (1) proliferative endometrium (n = 4), (2) proliferative glands and decidualized stroma (n = 1), (3) endometritis (n = 1), and (4) luteal insufficiency (n = 2). In the second cycle, 20% (2/10) of the biopsies demonstrated luteal insufficiency. Forty-five percent (10/22) of the first two cycles after spontaneous abortion demonstrated abnormal endometrial histology, with the first appearing more abnormal than the second (P = 0.06). Two conceptions occurred during the study period; both were uneventful term pregnancies. These findings suggest that a large proportion of the first two menstrual cycles after spontaneous abortion and curettage are abnormal, with the first cycle being more frequently abnormal than the second.

Prostaglandin F2 alpha synthesis and metabolism by luteal phase endometrium in vitro.

Differences in prostaglandin (PG) F2 alpha synthesis and degradation were sought between early luteal endometrium (histology day 15 to 22, n = 6) and late luteal endometrium (histology day 23 to 28, n = 6). In addition, alterations in PGF2 alpha synthesis and degradation in response to 17 beta-estradiol (E2) and progesterone (P) were examined to clarify the mechanism of steroid modulation of endometrial PG production (n = 12). Endometrium was maintained in tissue culture and the concentration of PGF2 alpha and 13,14 dehydro-15 keto F2 alpha (DHKF2 alpha) was determined in spent media by radioimmunoassay. Prostaglandin F2 alpha and DHKF2 alpha output from luteal endometrium exposed to P and E2 + P were both significantly reduced when compared with no addition or E2 treatments. This implies that the modulation of PGF2 alpha output by P in vitro is secondary to altered synthesis. There was an increase in PGF2 alpha output from late luteal endometrium when compared with early luteal endometrium in the P and E2 + P treatments, but DHKF2 alpha remained unchanged. These data imply that the temporal increase in PGF2 alpha output is the result of alterations in both PG synthesis and catabolism.

A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis.

This study was initiated to test the hypothesis that treatment with clomiphene citrate (CC) and intrauterine insemination (IUI) results in increased fecundity when compared with periovulatory intercourse in couples with either unexplained infertility or surgically corrected endometriosis. Sixty-seven couples entered a randomized, prospective trial comparing CC/IUI with observation. During the study, there were 14 pregnancies in 148 treated cycles (fecundity = 0.095) compared with 5 pregnancies in 150 untreated cycles (fecundity = 0.033). Using life-table analysis and the log-rank test, the difference in fecundities was statistically significant. Pregnancy outcome was not significantly different between the two groups. When comparing conception with nonconception cycles during treatment, no differences between the size of the lead follicle or the number of dominant follicles was detected. We conclude that treatment with CC/IUI improves fecundity in couples with unexplained infertility or surgically corrected endometriosis.

Spontaneous uterine rupture during pregnancy after treatment of Asherman's syndrome.

The treatment of Asherman's syndrome is often complicated by uterine perforation during hysteroscopic correction. We describe the first reported case of spontaneous uterine rupture with resultant hemorrhage during pregnancy after surgical treatment of Asherman's syndrome. This complication mandates close monitoring of these patients during pregnancy.

Early transvaginal ultrasound following an accurately dated pregnancy: the importance of finding a yolk sac or fetal heart motion.

Our goals were to determine the prognostic value of a yolk sac or fetal heart motion seen during an early accurately dated transvaginal ultrasound (TVU). We reviewed 225 consecutive pregnancies for fetal heart motion data. Furthermore, 63 pregnancies following in-vitro fertilization were reviewed for yolk sac information. The TVU was performed between 5 and 6 weeks following presumed conception (heart motion data) and between 22 and 32 days following in-vitro fertilization (yolk sac data). Pregnancies were followed until an ongoing pregnancy or spontaneous abortion was documented. The presence of a yolk sac between 22 and 32 days from fertilization was associated with the development of fetal heart motion in 94% of cases. The absence of the yolk sac by 32 days after fertilization was always associated with a poor outcome. In women < 36 years of age, the presence of fetal heart motion was associated with a spontaneous abortion in only 4.5% of the cases. However, the incidence of spontaneous abortion following fetal heart motion increased to 10% in women 36-39 years and 29% in women > or = 40 years of age. The presence of heart motion should not be considered a reassuring sign in the older woman. These data have implications regarding early embryology and the counselling of infertility patients.

CA-125 secretion by luteal phase endometrium in vitro.

The source of CA-125 in normal women and the mechanisms which control CA-125 production remain to be defined. This study was initiated to examine the pattern of secretion of CA-125 from luteal phase endometrium. Endometrial samples were obtained during the early luteal phase (histological days 16-18) and late luteal phase (histological days 25-27) from ovulatory women with a laparoscopically normal pelvis. The tissue was maintained in explant culture using Trowell's T-8 medium with either no additions (NA), progesterone (P), oestradiol (E2), or E2 + P. The concentration of CA-125 in spent media from the second day in culture was determined by immunoradiometric assay. In early luteal endometrium, the concentration of CA-125 in spent media from the NA treated wells was significantly higher than when the endometrium was exposed to either P or E2 + P. Similar differences were noted between treatments for the late luteal endometrium. Within each treatment, there was a higher concentration of CA-125 in the spent media from the late versus the early luteal endometrium. We conclude that the endometrium is a potential source of serum CA-125 and that endometrial CA-125 is suppressed by P in both the early and the late luteal phase. Further, there appears to be an increase in endometrial CA-125 secretion from the early to the late luteal phase.

Pituitary response to early follicular-phase minidose gonadotropin releasing hormone agonist (GnRHa) therapy: evidence for a second flare.

PURPOSE: Our purpose was to determine the pituitary response to minidose follicular-phase GnRHa and see if a second flare can be achieved. METHOD: A prospective, consecutive series of 12 couples with tubal-factor infertility underwent 14 cycles of minidose GnRHa. Women were given a 25- or 50-migrograms dose of leuprolide acetate (LA) on cycle days 2 and 5. On cycle days 3 and 4 no LA was given but 2 ampoules of pure follicle stimulating hormone (FSH) was administered. Beginning day 6, a combination of LA and FSH was administered. RESULTS: Following a dose of only 25 micrograms of LA on cycle day 2, mean FSH, LH, and E2 levels were significantly elevated over the baseline levels. Following no LA on cycle day 3 or 4, a repeat dose of 25 micrograms LA caused a second flare of LH and E2 on cycle day 6. Of the 14 cycles, 6 were canceled because of poor stimulation. Two of the eight patients who underwent retrieval delivered a live birth. CONCLUSIONS: This is the first study to examine both the pituitary response and the recovery time from minidose follicular-phase GnRHa. An extremely small dose of LA is needed to cause a pituitary flare of gonadotropins. Following a flare from 25 micrograms of LA on cycle day 2, the pituitary is able to recover and respond with a repeat flare on cycle day 5.

Predictors of success after embryo transfer: experience from a single provider.

OBJECTIVE: Our goal was to examine the variables present at the time of embryo transfer and to determine their effects on the clinical pregnancy rate. STUDY DESIGN: All fresh and frozen embryo transfers during a 3-year period in a university-based in vitro fertilization program were examined. Female age, previous in vitro fertilization attempt, diagnosis, embryo number and quality, transfer technique, and presence of a clinical pregnancy were recorded for each couple. Logistic regression analyses were performed both univariately and multivariately to determine the association between a clinical pregnancy and the independent variables. RESULTS: All transfers during the study period were included in the analysis. The four primary diagnoses were pelvic or tubal disease, male factor infertility, unexplained infertility, and endometriosis. The 46 frozen embryo transfers had a clinical pregnancy rate similar to that among the 159 fresh embryo transfers and were therefore included in the analysis. One variable was found to significantly affect the outcome, the number of high-grade embryos placed. The presence of a previous failed embryo transfer tended to lower the success rate for future attempts; however, this result did not reach statistical significance. The catheter type and the transfer difficulty did not affect outcome. CONCLUSION: The two most important variables for predicting a clinical pregnancy are a first-time transfer and the number of high-grade embryos placed. Neither the type of embryo transfer catheter used nor the diagnosis affected outcome. In this small sample difficult embryo transfers did not diminish the chance for a successful outcome.

Molar pregnancy coexisting with a normal fetus: a case report.

Molar pregnancy with a coexisting live fetus is a rare occurrence. We present morphologic and cytogenetic analysis of a recent case. Cytogenetic studies revealed a 46, XX karyotype for the fetus, the normal placenta, and the abnormal placenta. Chromosome banding studies confirmed the presence of maternal and paternal chromosomes in all three tissues. These studies favored the possibility that both tumor and fetus arose from a single gestation. Subsequently, the patient required chemotherapy for low-risk, metastatic trophoblastic disease.

Maternal hypothermia: an unusual complication of magnesium sulfate therapy.

Reported is a case of maternal hypothermia associated with magnesium sulfate therapy for treatment of preterm labor. Hypothermia was accompanied by fetal and maternal bradycardia. After discontinuation of magnesium sulfate infusion, maternal temperature, pulse, and fetal heart rate gradually returned to normal. No adverse effects were noted on either maternal or fetal outcome.

Antenatal diagnosis and management of monoamniotic twins.

Double survival of monoamniotic twins is rare. Three consecutive cases in which double survival occurred are presented. Accurate antenatal diagnosis, intensive fetal surveillance, and operative delivery should improve neonatal outcome.

Hydrops fetalis associated with immunologic and nonimmunologic factors.

Described is a pregnancy complicated by severe Rh sensitization and hydrops fetalis which was managed aggressively with frequent intrauterine transfusions initiated at 21 1/2 weeks of gestation. No improvement or only temporary improvement of the fetal hydrops was observed after each intrauterine transfusion. Postmortem examination of the infant revealed the additional presence of nonimmunologic factors involved such as pulmonic atresia and lung hypoplasia. In cases of severe Rh sensitization associated with persistent fetal hydrops despite frequent intrauterine transfusions, the presence of coexistent factors for nonimmunologic fetal hydrops should be considered.