Minimal precycle testing and ongoing cycle monitoring for in vitro fertilization and fresh pre-embryo transfer do not compromise fertilization, implantation, or ongoing pregnancy rates.

OBJECTIVE: We sought to assess the fertilization, implantation, and ongoing pregnancy rates with a minimal precycle and ongoing cycle monitoring protocol for in vitro fertilization and embryo transfer. STUDY DESIGN: Retrospective review was conducted of 103 consecutive cycles of fresh in vitro fertilization and embryo transfer from 1996 to 1998. Precycle screening included semen analysis without strict morphologic analysis, and hysterosalpingography-sonohysterography within the last year. Serum prolactin, serum thyroid-stimulating hormone, reactive plasma reagin, human immunodeficiency virus, rubella titer, blood type, hepatitis B surface antigen, and hepatitis C antibody testing was performed on all patients within 3 months of cycle initiation. Women > or =37 years old underwent clomiphene challenge testing. The monitoring protocol included the following: baseline transvaginal ultrasonography after 12 to 14 days of midluteal gonadotropin-releasing hormone agonist down-regulation to assess endometrial thickness and adnexal appearance, transvaginal ultrasonography for follicle evaluation at 7 and 10 days, serum estradiol assay if > or =20 follicles, quantitative beta-human chorionic gonadotropin 12 to 14 days after pre-embryo transfer, repeat quantitative beta-human chorionic gonadotropin 3 to 5 days later, and transvaginal ultrasonography for intrauterine gestational sac confirmation 7 to 9 days after the initial positive pregnancy test result. The dose of gonadotropin used remained constant unless the sonogram obtained on day 7 indicated a suboptimal response (<3 follicles each, with an average diameter of 10 to 12 mm) or hyperresponse (> or =15 follicles with an average diameter of 10 to 12 mm). RESULTS: The per embryo implantation rate (fetal cardiac activity) was 13.1%, and the live birth rate per 100 pre-embryo transfers was 31.5 for patients < or =40 years old. The average number of pre-embryos transferred was 3.1. The singleton pregnancy rate was 71%, and there were no multiple gestations greater than twins. The mean number of oocytes fertilized was 66%. There was 1 case of failed fertilization with intracytoplasmic sperm injection. There were two other cases of failed fertilization. One case of severe ovarian hyperstimulation occurred in spite of cryopreservation of all embryos. CONCLUSIONS: In vitro fertilization and embryo transfer can be accomplished with minimal precycle testing and ongoing cycle monitoring without compromising fertilization, implantation, and ongoing pregnancy rates. This results in reduced overall costs for couples.

Serum progesterone and endovaginal sonography by emergency physicians in the evaluation of ectopic pregnancy.

OBJECTIVE: To determine a discriminatory level for serum progesterone (SP) in pregnant patients with no definite intrauterine pregnancy (IUP) on endovaginal ultrasonography (US) in the differentiation of ectopic pregnancy from normal IUPs. METHODS: A prospective observational study in a convenience sample of women at risk for ectopic pregnancy was performed at an urban teaching hospital from May 1991 until May 1994. Women aged > or =18 years presenting to the ED with a positive pregnancy test in combination with pelvic or abdominal pain, vaginal bleeding, orthostasis, adnexal mass or tenderness, or any historical risk factor for ectopic pregnancy were eligible. Hypotensive or unstable patients were excluded. Endovaginal US was performed and patients with no definite IUP had a serum beta-hCG and SP measured. RESULTS: 314 patients were enrolled, with 14 excluded for lack of follow-up or incomplete SP data, yielding 300 patients. The initial endovaginal US diagnoses included 169 definite IUP, 31 abnormal IUP, 5 definite ectopic pregnancy, and 95 no definite IUP. 68/95 had SP measured, with values of 22.8 +/- 13.4 ng/mL (mean +/- SD) for IUP; 4.9 +/- 6.5 for spontaneous abortion, and 7.5 +/- 7.2 for ectopic pregnancy. The mean values were significantly different (2-tailed t-test) for ectopic pregnancy vs IUP and for spontaneous abortion vs IUP. An SP of > or =11 ng/mL (sensitivity 91%; specificity 84%) was post hoc the best cutoff value for suggesting an IUP when the endovaginal US was not definite for IUP. CONCLUSIONS: SP cannot reliably discriminate ectopic pregnancy vs spontaneous abortion in pregnant patients with no definite IUP on endovaginal US; however, a low SP (<11 ng/mL) in this sonographic category suggests an abnormal pregnancy.

Outcome analysis of a protocol including bedside endovaginal sonography in patients at risk for ectopic pregnancy.

STUDY OBJECTIVES: To determine whether bedside endovaginal sonography (EVS) performed by emergency physicians reduces complications associated with ectopic pregnancy (EP) including missed EP and EP rupture. METHODS: Our setting was an urban trauma center emergency department. We assembled a prospective convenience sample (n=314) with a historical EP control group (n=56) of women 18 years or older with a positive pregnancy test and any signs, symptoms, or risk factors for EP. Bedside EVS for all subjects and immediate quantitative serum human chorionic gonadotropin determination for patients with no definite intrauterine pregnancy by EVS. RESULTS: Retrospective chart review identified 56 EP patients in the historical control group who had had no bedside EVS. Twenty-four of these patients (43%; 95% confidence interval [CI], 30% to 56%) were discharged from the ED, 12 of whom (50%; 95% CI, 30% to 70%) were later categorized as having ruptured EP. During the prospective study period, 40 patients were diagnosed as having EP; 11 (28%; 95% CI, 14% to 42%) were discharged from the ED (P=NS), and only 1 (9%; 95% CI, 0% to 26%) of the discharged patients was later determined to have a ruptured EP (P<.05). CONCLUSION: An EP protocol incorporating bedside EVS performed by emergency physicians significantly reduced the incidence of discharged patients with subsequent EP rupture, compared with historical controls.

Ultrasonographic examination by emergency physicians of patients at risk for ectopic pregnancy.

OBJECTIVE: To evaluate a diagnostic protocol that includes the early use of endovaginal sonography (EVS) by emergency physicians of patients at risk for ectopic pregnancy. METHODS: During this prospective study, pregnant patients > or = 18 years old and at risk for ectopic pregnancy were assessed. Emergency physicians who had completed a training program performed EVS on a convenience sample of eligible women. Clinical disposition was based on predetermined clinical, laboratory, and ultrasonographic criteria. The EVS examinations were reviewed on video by a gynecologist whose interpretation was correlated with the emergency physician EVS readings and with the final clinical diagnoses. Quantitative serum beta-human chorionic gonadotropin (beta hCG) levels were determined for patients who had no definite intrauterine pregnancy (IUP) on EVS. RESULTS: Of 152 patients studied during a 12-month period, four were lost to follow-up. Emergency physician ultrasonographic diagnoses included: definite IUP, 87/148 (59%); probable abnormal IUP, 17/148 (11%); definite ectopic pregnancy, 3/148 (2%); and no definite IUP, 41/148 (28%). The gynecologist agreed with 93% of the initial interpretations. Twelve of 16 patients who had the final diagnosis of ectopic pregnancy were admitted from the ED with this diagnosis. The ultrasonographic diagnosis of the other four was no definite IUP, and no mass or free fluid. For the latter four patients, the presenting serum beta hCG level was < 2,000 mIU/mL (First International Reference Preparation). They were diagnosed as having ectopic pregnancy after serial outpatient EVS and beta hCG measurements. CONCLUSIONS: The application of EVS to emergency practice appears promising. Emergency physicians trained in its use and who apply this diagnostic tool in conjunction with a defined protocol can stratify the risk of patients who have the potential for ectopic pregnancy.

Diagnosis of ectopic pregnancy: endovaginal vs transabdominal sonography.

During a 25-month period, 193 women with the clinical diagnosis of suspected ectopic pregnancy had transabdominal and endovaginal sonograms. Most had quantitative determinations of serum human chorionic gonadotropin (HCG). Endovaginal sonography was diagnostic of ectopic pregnancy in 23 (38%) of the 60 patients with surgically proved ectopic pregnancies: transabdominal sonography was diagnostic in 13 patients (22%). All 83 intrauterine pregnancies were identified with endovaginal sonography, compared with 34 identified with transabdominal sonography. Endovaginal sonography was somewhat more helpful in the diagnosis of missed abortion and blighted ovum. Eighty endovaginal sonograms were classified as indeterminate as compared with 141 transabdominal studies. This indeterminate group included patients with complete abortions, ectopic pregnancies without sonographic evidence of an extrauterine gestation, incomplete abortions, and patients with subsequent negative serum levels. As in prior reports, endovaginal sonography was superior to transabdominal sonography in the evaluation of suspected ectopic pregnancies. Overall, endovaginal sonography was diagnostic in 113 patients, whereas transabdominal sonography was diagnostic in 52 patients. The finding of an extrauterine fetal pole or embryo was diagnostic for an ectopic pregnancy. Pelvic fluid, the appearance of the endometrium, and a single positive serum HCG determination were not helpful in making the diagnosis of ectopic pregnancy.

The relationship of insulin to sex hormone-binding globulin: role of adiposity.

The role of adiposity in the relationship of insulin to sex hormone-binding globulin (SHBG) concentration was examined in 31 healthy premenopausal women of varying body weight. Fat mass was estimated by hydrostatic weighing. Concentrations of SHBG and testosterone (T) and cumulative insulin response during an oral glucose tolerance test were measured. The cumulative insulin response was inversely related to SHBG (r = -0.56, P less than 0.01). The relationship between SHBG and cumulative insulin response remained significant (r = -0.47, P less than 0.01) after adjusting for fat mass and T. The fat mass correlated significantly with SHBG (r = -0.51, P less than 0.01). The relationship of SHBG to fat mass remained significant after adjusting for T (r = -0.45, P less than 0.01). However, the relationship between fat mass and SHBG was no longer significant (r = -0.34, P greater than 0.05) after adjusting for cumulative insulin response. Hyperinsulinemia may play an important role in the progressive reduction of SHBG observed with increasing adiposity.

The relative contributions of hepatic and peripheral tissues to insulin resistance in hyperandrogenic women.

Insulin resistance is associated with hyperandrogenic states. To determine the mechanisms by which androgen excess can affect insulin action, we studied insulin sensitivity in five nonobese hyperandrogenic women and six normal women. After oral glucose administration, the hyperandrogenic women had higher serum insulin concentrations than the normal women (P = 0.05). The mean cumulative peripheral serum insulin response in the hyperandrogenic women [79.6 +/- 30.8 (+/- SD) nmol/L.300 min] was significantly greater than that in the normal women (46.6 +/- 15.1 nmol/L.300 min; P less than 0.05). In the basal state and during hyperinsulinemic (20 mU/min.m2) euglycemic clamp studies serum insulin levels were similar in the two groups. Basal and insulin-mediated suppressions of hepatic glucose production determined from [3-3H]glucose specific activity were similar in the two groups. Peripheral glucose utilization was markedly diminished in the hyperandrogenic women compared to that in the normal women (27.8 +/- 6.7 vs 48.9 +/- 12.8 mumol/min.kg fat-free mass; P less than 0.01). We conclude that the insulin resistance in nonobese hyperandrogenic women is due to peripheral, but not hepatic, resistance to the action of insulin. This marked peripheral insulin resistance may result from the effects of hyperandrogenemia on skeletal muscle fiber morphology and metabolism.

In vitro fertilization patient presenting in hemorrhagic shock caused by unsuspected heterotopic pregnancy.

A 30-year-old woman who had undergone in vitro fertilization and embryo transfer (IVF-ET) presented to the emergency department in hemorrhagic shock 4 weeks after a spontaneous abortion. She was found to have a ruptured uterus caused by an unsuspected second pregnancy located in the cornual region of the uterus. Women undergoing IVF-ET are at a higher risk for multiple pregnancies, ectopic pregnancies, and heterotopic pregnancies.

Testicular leydig cell hyperplasia as a cause of familial sexual precocity.

Testicular Leydig cell hyperplasia was observed in two brothers presenting with progressive sexual precocity at 2 yr of age. Virilization was shown to result from increased secretion rather than decreased clearance of gonadal testosterone. Testosterone hypersecretion appeared to be gonadotropin independent, as basal and gonadotropin-releasing hormone-induced serum LH concentrations were low by both RIA and bioassay. Adrenal steroidogenesis was demonstrated to be normal by ACTH stimulation, dexamethasone suppression, and split adrenal venous function tests. Testicular histology revealed immature reproductive structures in the 2 yr old, but advanced spermatogenesis in the 3 yr-old brother. The etiology of both Leydig cell hyperplasia and reproductive testicular maturation in the absence of significant gonadotropin secretion remains to be established.