The possible influence of increased body mass index on the clinical efficacy of standard human chorionic gonadotropin dosage.

OBJECTIVES: To evaluate whether the efficacy of standard (10,000 IU) hCG dosage is BMI dependent. PATIENTS & METHODS: During the study period, body mass index (BMI) was recorded in 261 consecutive women enrolled in our ICSI program. Women in the 90th BMI percentile were compared with those in the 10th percentile. The number and percent of mature metaphase-II (M-II) oocytes were considered as the outcome measure. RESULTS: Mean BMI of the 10th and 90th percentile groups were 18.2 +/- 0.7 kg/m2 (n = 26) and 32.8 +/- 2.2 kg/m2 (n = 27), respectively. There were no differences between the groups in mean patients age, number of gonadotropin ampoules used, mean number of oocytes retrieved or the number and percentage of mature M-II oocytes. CONCLUSIONS: Standard (10,000 IU) hCG dosage is adequate to induce final oocyte maturation in IVF patients regardless of their BMI. This may imply that this hCG dosage is much higher than the dosage that is actually required.

Early endometrial changes following successful implantation: 2 and 3-dimensional ultrasound study.

OBJECTIVE: To study of the possible role of ultrasound (US) measurements of the endometrium in the prediction of IVF outcome. PATIENTS AND METHODS: 28 infertile women underwent US measurements of endometrial thickness and volume on day of ET and two weeks later. US measurements were compared between day of ET and two weeks later, and between those who conceived and those who did not. RESULTS: While in the group of patients who conceived (n = 7) endometrial thickness and volume rose significantly between day of hCG and two weeks later, no differences were observed in patients (n = 21) who did not. CONCLUSION: The dynamic changes in endometrial volume and thickness between day of ET and two weeks later may predict IVF treatment outcome.

Ovarian hyperstimulation without elevated serum estradiol associated with pure follicle-stimulating hormone-secreting pituitary adenoma.

We report a unique case of a 28-yr-old woman with a gonadotroph adenoma secreting FSH, presented with ovarian hyperstimulation, without elevation of serum estradiol. She presented with abdominal pain and large ovaries (both 10 cm in diameter) with multiple follicular cysts shortly after discontinuing oral contraceptive pills. She had a supranormal PRL level of 71 microg/liter (normal, <20), FSH of 8.4-9.2 IU/liter (normal for follicular phase, 2.4-10), LH of 0.01 IU/liter (normal, 1.6-9.3), estradiol of 108 pmol/liter (normal for follicular phase, 80-790), and free alpha-subunit level of 0.11 microg/liter (normal, <1.8). A nuclear magnetic resonance study revealed invasive pituitary macroadenoma, 30 mm in diameter. Dopamine agonist (cabergoline) treatment normalized serum PRL but had no affect on FSH levels. A transsphenoidal surgery was performed, and most of the adenoma was resected. One month after surgery the patient resumed menstruation, and the hormonal profile included serum FSH of 6.3 IU/liter, LH of 2.1 IU/liter, estradiol of 156 pmol/liter, and PRL of 10 microg/liter. The excised adenoma tissue exhibited intense immunostaining for FSH and secreted this hormone to culture medium. Stimulation with TRH (both in vivo preoperatively and in vitro study of the excised tumor) had no effect on FSH secretion from the adenoma. Estradiol did not suppress FSH release from cultured adenoma cells. Patient serum samples showed significant FSH bioactivity when tested in a human granulosa cell line. This case is remarkable because the ovarian hyperstimulation related to the FSH-secreting adenoma was not associated with high levels of serum estradiol, probably due to insufficient LH production by the normal pituitary. Thus, it supports the two-cell, two-gonadotropin theory, that both FSH and LH are necessary for normal ovarian estrogen production.

Differential diagnosis of the nonvisualized fetal urinary bladder by transvaginal sonography in the early second trimester.

OBJECTIVE: To describe the pathologic situations associated with the persistently nonvisualized fetal urinary bladder in the early second trimester. METHODS: We analyzed retrospectively 13,458 ultrasound examinations performed between 12-16 weeks' gestation in search of fetal malformations. Seventy percent of the patients were at low risk and 30% comprised a high-risk group for the detection of fetal anomalies. RESULTS: Seven cases of persistent nonvisualization of the fetal urinary bladder were detected by transvaginal sonography among 13,458 fetuses. In one case bladder exstrophy, and in another bilateral multicystic dysplastic kidneys were diagnosed by postabortal examination. Five cases were associated with bilateral renal agenesis. CONCLUSION: When one fails persistently to demonstrate the fetal urinary bladder during an examination lasting 30 minutes or longer, urinary tract pathology should be highly suspected. Failure to visualize the bladder may be associated with bladder exstrophy, bilateral renal agenesis, or late onset of bilateral multicystic dysplastic kidneys.

Doppler study of the fetal cardiac function in prolonged pregnancies.

OBJECTIVE: To evaluate the association between fetal cardiac function and amniotic fluid index (AFI) in postterm fetuses, and to determine if changes in fetal cardiac function precede the occurrence of nonreassuring intrapartum fetal heart rate (FHR) patterns. METHODS: Forty-five otherwise low-risk pregnant women between 41 and 43 weeks' gestation were studied longitudinally. Gestational age was confirmed in all patients by ultrasound before 20 weeks' gestation. Each subject had two or three tests performed every 3-4 days, including a non-stress test, a biophysical profile, and Doppler studies of the aortic and pulmonic outflow tracts. Aortic and pulmonic artery flow velocity waveforms were recorded slightly distal to the valves. Peak velocity, velocity time integral, and heart rate were calculated from the flow velocity waveforms we obtained. The change in AFI and aortic and pulmonic peak velocity and [velocity time integral] x [heart rate] were calculated for each fetus. RESULTS: Labor was induced at 42 weeks' gestation in 20 patients, and 17 entered labor spontaneously. Changes in AFI, observed during the follow-up period, correlated significantly with changes in aortic peak velocity (r = 0.54, P < .01) and with aortic outflow [velocity time integral] x [heart rate] (r = 0.60, P < .001) but not with pulmonic peak velocity and [velocity time integral] x [heart rate]. The decrease in aortic peak velocity and aortic and pulmonic [velocity time integral] x [heart rate] was significantly higher (P < .01) in eight fetuses that developed a nonreassuring intrapartum FHR (reduced FHR variability, late decelerations, and severe variable decelerations) than in those who had an uneventful labor. CONCLUSION: In prolonged pregnancies, cardiac function deteriorates in fetuses that develop a nonreassuring intrapartum FHR, and the changes in the left cardiac function correlate with changes in AFI.

The difference between septated and nonseptated nuchal cystic hygroma in the early second trimester.

OBJECTIVE: To compare nonseptated and septated cystic hygromas in terms of morphologic appearance and prognosis. METHODS: During a 5-year period, 125 cases of nonseptated cystic hygroma were detected by transvaginal sonography among 7582 sonographic fetal scans (1.6%) in the first and early second trimesters. Twenty-five cases of septated cystic hygroma were detected in the same population. Fetal karyotype abnormalities; sonographic, morphologic, and histologic appearance; and pregnancy outcome were compared between the groups. RESULTS: Whereas 98% of the nonseptated cystic hygromas were transient, only 44% of the 25 septated cystic hygromas were transient. Six of the 106 cases of nonseptated cystic hygroma that underwent karyotyping were dyskaryotic (5.7%), compared with a 72% (18 of 25) aneuploidy rate in the septated cystic hygromas. Only two cases of hydrops fetalis (1.7%) occurred among the nonseptated cystic hygromas, versus 40% (ten of 25) in the septated cystic hygromas. Fifteen percent of the nonseptated cystic hygromas had associated anomalies (17 of 115) versus 52% (13 of 25) in the septated counterpart. As compared with the septated group, the nonseptated cystic hygromas had a different sonographic, morphologic, and histologic appearance. The live-birth rate was 94% (108 of 115) in the nonseptated cystic hygromas, versus only 12% in the septated group. CONCLUSIONS: This study confirms our previous suggestion that nonseptated cystic hygromas differ from septated lesions, not only in location and morphologic appearance, but also in prognosis.

Fibrin glue improves pregnancy rates in women of advanced reproductive age and in patients in whom in vitro fertilization attempts repeatedly fail.

OBJECTIVE: To evaluate the possible contribution of fibrin sealant to the ET stage of IVF. DESIGN: Case-control study. SETTING: An assisted reproductive technology unit that performed 2,535 treatment cycles from 1996-1997. PATIENT(S): All consecutively seen patients who underwent ET from January 1996 to September 1997. INTERVENTION(S): All women who underwent ET with the aid of fibrin sealant during the study period were compared with those who underwent standard ET (controls). Thereafter, a case-control study was conducted on the first consecutively seen 174 women who underwent ET with fibrin sealant and a control group that was matched for age and number of previous unsuccessful cycles. MAIN OUTCOME MEASURE(S): Patient age, number of previous unsuccessful IVF attempts, number of embryos transferred, and pregnancy rates. RESULT(S): During the study period, ET was performed with fibrin sealant in 265 women and by the standard procedure in 1,402 women. Women in the fibrin sealant group were significantly older. The pregnancy rate was not significantly different between the groups in the whole-cohort study (20.4% versus 23.1%), but it was significantly higher in the fibrin sealant group in the case-control study (25.3% versus 14.9%). This also was true when the older women (>35 years) and the women with > or =4 previous failed IVF attempts were analyzed separately (23.2% versus 9.8% and 26.1% versus 13.4%, respectively). CONCLUSION(S): The use of fibrin sealant in ET appears to be beneficial in women of advanced reproductive age and in patients in whom IVF attempts repeatedly fail.

Early diagnosis and successful nonsurgical treatment of viable combined intrauterine and cervical pregnancy.

Cervical pregnancy is a rare form of EP often resulting in an obstetric catastrophe. We report a case of a combined viable IUP and cervical pregnancy resulting from IVF-ET treatment and which was diagnosed during the 7th week of gestation. Nonsurgical treatment consisting of selective intra-arterial catheterization and administration of MTX directly into the uterine arteries was carried out successfully. Complications were avoided, and the patient's reproductive capability was preserved.

A severe case of ovarian hyperstimulation syndrome despite the prophylactic administration of intravenous albumin.

OBJECTIVE: To evaluate the role of the recently suggested IV administration of human albumin solution as an effective preventive measure of severe ovarian hyperstimulation in high-risk patients. CASE: Presented here is, to the best of our knowledge, the first case of early severe ovarian hyperstimulation necessitating early transabdominal aspiration of ascites and intensive fluid and colloid (dextran and albumin) replacement, which developed despite administration of IV human albumin solution in an attempt to prevent severe ovarian hyperstimulation. CONCLUSIONS: Because IV albumin does not prevent severe ovarian hyperstimulation in absolute terms, its use in high-risk patients should not lead one astray. Further research should be directed at investigating the fundamental cause of ovarian hyperstimulation syndrome and developing a reliable predictive test for this complication.

Double (consecutive) transfer of early embryos and blastocysts: aims and results.

OBJECTIVE: The aim of this study was to evaluate the consecutive transfer approach of early embryos and blastocyst(s). DESIGN: Case-control study. SETTING: Public assisted reproduction technology unit. PATIENT(S): The study population consisted of three groups. In Group 1, a double transfer was performed on 136 consecutive women, that is, a standard transfer of embryos on day 2 or 3, and a second transfer of a blastocyst(s). In Group 2, an early transfer of only two embryos and a second transfer of one blastocyst were performed on 29 women from group 1 who had more than three high-quality embryos available for early transfer. In Group 3, a single early transfer was performed on 139 consecutive women who received three high-quality embryos (controls). INTERVENTION(S): Early embryo transfer, extended culture of the spare embryos, and a second transfer of a blastocyst(s). MAIN OUTCOME MEASURE(S): Implantation and pregnancy rates. RESULTSs): No differences were detected among the three groups in either pregnancy or implantation rates (pregnancy: 36.8%, 41.4%, and 37.4%, respectively; implantation: 14.6%, 19.9%, and 19.8%, respectively). CONCLUSION(S): The double (consecutive) transfer of early embryos and blastocyst(s) does not offer any advantage over the traditional early transfer. This may be from the adverse effect of the second transfer on the implantation process.

Predictive value of transvaginal sonography performed before routine diagnostic hysteroscopy for evaluation of infertility.

OBJECTIVE: To compare transvaginal sonography with hysteroscopy for the evaluation of intrauterine disorders. DESIGN: Clinical study. SETTING: Academic research environment. PATIENT(S): Patients who were undergoing initial evaluation for primary or secondary infertility or investigation after three failed IVF attempts. INTERVENTION(S): Transvaginal sonography was performed, followed by hysteroscopy, between January 1998 and April 1999. The endometrial findings at sonography were compared with those at hysteroscopy, which served as the gold standard. The characteristic sonographic features of intrauterine adhesions were defined. MAIN OUTCOME MEASURE(S): Intrauterine adhesions, endometrial polyps. RESULT(S): The sensitivity, specificity, and positive and negative predictive values for transvaginal sonography in detecting abnormal uterine cavities were 100%, 96.3%, 91.3%, and 100%, respectively. The corresponding values for the specific diagnoses of intrauterine adhesions and endometrial polyps were 80%, 100%, 100%, and 97%, and 71.4%, 100%, 100%, and 97.1%, respectively. On transvaginal sonography, intrauterine adhesions appeared as hyperechoic endometrial foci and were differentiated from endometrial polyps by their irregular shape and more precise localization. The performance of transvaginal sonography at midcycle (three-layer endometrium) rather than after menstrual cessation (endometrial thickness <3 mm) enabled better imaging of small intrauterine adhesions. CONCLUSION(S): A regular myometrial-endometrial interface and homogeneous endometrial structure on transvaginal sonography congruent with the phase of the menstrual cycle indicated a normal endometrium and precluded the need for diagnostic hysteroscopy. Transvaginal sonography may be used as the initial diagnostic procedure to select patients for hysteroscopy.

The role of purified follicle stimulating hormone therapy in the male partner before intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the impact of long-term purified FSH (pFSH) therapy in male partners before intracytoplasmic sperm injection (ICSI). DESIGN: Prospective, randomized, controlled study. SETTING: Large university-based IVF unit. PATIENT(S): Seventy-eight patients made up the study and control groups (39 patients each). All patients had severe male factor infertility. INTERVENTION(S): Induction of ovulation, oocyte retrieval, ICSI, and ET were carried out in both groups. In the study group, male partners received pFSH (75 IU FSH, <1 IU LH) for > or = 50 days before oocyte retrieval. MAIN OUTCOME MEASURE(S): Fertilization rate, embryo quality, implantation and pregnancy rates. RESULT(S): Fertilization and pregnancy rates were higher in the study group (68% and 35.9%, respectively) were higher than in the control group (59% and 17.9%, respectively), although the differences did not reach statistical significance. The implantation rate was significantly higher in the study group (15.5% versus 6.5%). The study group showed a trend toward a higher number of better-quality embryos per transfer (mean +/- SD, 2.2 +/- 1.6 versus 1.6 +/- 1.6). CONCLUSION(S): Purified FSH therapy in male partners before ICSI improves implantation rate. Improved embryo quality may be a contributory factor.

Morphology and clinical outcomes of embryos after in vitro fertilization are superior to those after intracytoplasmic sperm injection.

OBJECTIVE: To compare embryos obtained after IVF and intracytoplasmic sperm injection (ICSI) regarding morphology and the likelihood of achieving clinical pregnancy. DESIGN: Case-control study. SETTING: An IVF unit controlling 1,310 cycles in 1996. PATIENT(S): Women having a total of 477 IVF and 475 ICSI consecutive cycles. INTERVENTION(S): Ovarian stimulation, IVF-ET, or ICSI-ET for all couples. MAIN OUTCOME MEASURE(S): Number of grade-A embryos transferred, preclinical pregnancy losses, and clinical pregnancy rates in IVF and ICSI cycles. RESULT(S): In comparison with the ICSI group, the IVF group showed significantly more grade-A embryos available for transfer (mean, 2 +/- 1.6 versus 1.8 +/- 1.5), significantly fewer preclinical pregnancy losses (1.6% versus 4%), and significantly higher clinical pregnancy rates (25% versus 19.1%). CONCLUSION(S): Embryos obtained after IVF are superior to those obtained after ICSI in relation to embryo morphology and the likelihood of achieving clinical pregnancy.

Increased D-dimer levels in twin gestation.

In normal pregnancy, the hemostatic balance is displaced toward hypercoagulability. The elevation in plasma levels of coagulation factors VII, VIII, and X and fibrinogen and the increased concentrations of plasminogen activator inhibitors [1,2] may predispose individuals to thromboembolism, especially near term [1,3]. Because human multifetal gestation requires still greater physiological alterations, the imbalance in hemostasis is further exaggerated. It has been suggested that the changes in the coagulation system near term may even mimic low-grade disseminated intravascular coagulopathy [4]. However, for the majority of women with multifetal gestation, the coagulopathy observed in the laboratory is not clinically apparent [5]. Despite the large body of research on the physiological adaptation to pregnancy, relatively little is known of the biological adaptation in general and the hemostatic changes in particular associated with multiple gestation.

Pharmacokinetics of the progesterone-containing vaginal tablet and its use in assisted reproduction.

Natural progesterone, which is devoid of androgenic activity, is widely used in assisted reproduction for luteal and pregnancy support. The vaginal route has become the most established way to deliver natural progesterone because it is easily administered, avoids liver first-pass metabolism, and has no systemic side-effects. The vagina has a large potential for absorption, and through the 'uterine first-pass effect' vaginal administration results in higher uterine progesterone concentrations. We have investigated the pharmacokinetics of natural progesterone in the form of a vaginal tablet. A single dose of 100 mg resulted in a mean C(max) of 31.53 +/- 9.15 nmol/l with a T(max) of 6.92 +/- 3.12 h. The terminal half-life was 16.39 +/- 5.25 h. The pharmacokinetic data are discussed in relation to dose, age, and estrogen priming. Single-dose pharmacokinetics of 100 mg of progesterone vaginal tablets and gelatin capsules were evaluated over 24 h. Results indicated a similar mean T(max) of 6.92 +/- 3.12 and 6.23 +/- 6.57 h, respectively. However, a significantly higher C(max) was achieved by the vaginal tablet (31.95 +/- 9.15 and 23.85 +/- 9.57 nmol/l, respectively, P < 0.05). Continuous use of vaginal progesterone did not influence the hormonal, liver, or lipid profiles evaluated. There was no case of endometrial hyperplasia. The vaginal tablet was found to be well-tolerated, safe, and easily administered. In conclusion, progesterone-containing vaginal tablets have good pharmacokinetic properties and should be used for progesterone supplementation in IVF.

Twin gestation: is there a correlation between the location of the gestational sacs at the beginning of pregnancy, and the order of delivery.

OBJECTIVES: To determine whether there is a dynamic in the location of amniotic sacs in a twin gestation, during pregnancy. STUDY DESIGN: The study group comprised 63 twin pairs discordant for sex, who by vaginal sonography performed between 14 and 16 weeks' gestation, were characterized as first twin (opposite the internal os), and second twin. The order of delivery was recorded in the pregnancies that ended with vaginal birth. RESULTS: Thirty seven of 41 (90.2%) twins who were delivered vaginally (between 32 and 41 weeks' gestation), were born in the same order as that predicted by transvaginal sonography early in pregnancy. It was found that in this small series there was a dynamic in the amniotic sac location in twin gestations during pregnancy in only about 10% of the cases. CONCLUSIONS: In roughly 90% of twins, there is no dynamic in the location of the amniotic sacs during pregnancy, and the first twin at the beginning of pregnancy intrinsically remains.

Endometrial carcinoma in a post-menopausal woman with atrophic endometrium and intra-cavitary fluid: a case report.

Measurement of endometrial thickness by vaginal ultrasonography is used to detect post-menopausal women at risk for endometrial pathology. The efficacy of this procedure is doubtful in cases of intrauterine fluid accumulation, which is a common finding in this population. We present a case of endometrial carcinoma in an asymptomatic, post-menopausal woman with ultrasonographic imaging of an atrophic endometrium and intra-cavitary fluid. It may be suggested that, in a case of intrauterine fluid accumulation (IFA), endometrial biopsy should be performed regardless of the sonographic endometrial thickness, since the fluid may increase the intracavity pressure and can mask endometrial pathology.

Gestational diabetes and preterm labour: is glycaemic control a contributing factor?.

OBJECTIVES: (1) to evaluate the incidence of preterm delivery in patients with gestational diabetes mellitus; (2) to determine the association between glycaemic control and preterm delivery in these patients. STUDY DESIGN: (1) The incidence of spontaneous preterm singleton deliveries was determined in 550 intensively-treated patients with gestational diabetes mellitus. A total of 14 552 consecutive patients without gestational diabetes mellitus who delivered during the same interval served as a control population; (2) Glycaemic profiles (i.e., mean blood glucose, percent of hypoglycaemic [ < 60 mg/dl] and hyperglycaemic [ > 120 mg/dl] episodes) were compared in 34 patients with gestational diabetes mellitus who delivered preterm, and 68 matched controls with gestational diabetes mellitus who delivered at term. RESULTS: (1) The incidence of preterm delivery in gestational diabetics was similar to that found in the non-diabetic population (6.2% vs. 6.5%, respectively, P = 0.82; confidence limits: 0.65, 1.36); (2) women with gestational diabetes mellitus who delivered at term, or preterm had similar glycaemic profiles for both the entire treatment period and the week preceding delivery. CONCLUSIONS: (1) There is no increased risk for preterm delivery in intensively-treated gestational diabetes mellitus patients; (2) In a population such as this women with gestational diabetes mellitus who deliver preterm cannot be characterised by their glycaemic profile.

Single intrauterine fetal death (fetus papyraceus) due to uterine trauma in a twin pregnancy.

Fetus papyraceus is a rare condition. We describe the intrauterine fetal death with subsequent fetus papyraceus of one twin due to blunt maternal trauma in the second trimester of pregnancy. Blunt maternal trauma should raise the clinical suspicion of fetal death and dictate further observation; in a twin pregnancy, the possibility of a single fetal death should be investigated.

Pregnancy and multiple sclerosis: a 2-year experience.

OBJECTIVE: To present our experience with management of parturients with multiple sclerosis and to examine the role of intravenous immunoglobulin (IVIg) in the prevention of postpartum exacerbations of the disease. METHODS: Fifteen patients with multiple sclerosis with a relapsing-remitting course were followed during pregnancy and 6 months postpartum. To prevent postpartum exacerbations, 14 of the patients had received IVIg after delivery. RESULTS: None of the patients who received postpartum IVIg relapsed during the 6 months after delivery. None of the observed obstetric complications nor the operative deliveries could be related to the coexistence of multiple sclerosis. CONCLUSION: Postpartum IVIg treatment is beneficial in preventing acute childbirth-associated exacerbations in patients with relapsing-remitting multiple sclerosis. Furthermore, this disease does not seem to increase obstetric complications.