Outcome of pregnancy in 31 triplet gestations.

The course of gestation and labor and the outcome of 31 triplet pregnancies were analyzed. Early diagnosis is very important for improving the rate of fetal salvage in multiple pregnancy. The outcome of triplet pregnancies was better in the group of patients with induced ovulation than in the group with spontaneous ovulation. The most frequent antenatal complications were preterm labor (97%), pregnancy-induced hypertension (46%), and anemia (20%). In this series the favorable results were due to earlier diagnosis, prolonged hospitalization, and planned delivery, usually by cesarean section.

Diagnosis of rupture of the fetal membranes by glucose and fructose measurements.

A new method is presented for differentiating amniotic fluid from cervical mucus, based on differences in the respective carbohydrate concentrations present in these fluids. Glucose and fructose are present in high concentrations in cervical mucus during pregnancy, average values being 240 and 30.4 mg/100 ml, respectively. Their concentrations in amniotic fluid, however, are low, averaging 39 and 3.3 mg/ml, respectively. Examination of 215 women between 36 and 42 weeks' gestation, using either glucose or fructose values, revealed a high degree of discrimination between amniotic fluid and cervical mucus. The best results, however, were obtained by employing the calculated linear sum 3.32 log glucose plus log fructose for each sample. Inaccuracy rates were low in comparison to those of other diagnostic methods, such as pH values, ferning, and Nile blue sulfate staining. A further advantage of the method is that it remains fairly accurate even when the time interval between rupture of the membranes and the investigation exceeds 24 hours.

Diagnostic and prognostic value of retinal hemorrhages in the neonate.

Ocular fundi of 410 newborns were examined for retinal hemorrhages within 24 hours after delivery. The purpose of this study was to investigate whether the course of pregnancy and management of delivery influence the incidence of neonatal retinal hemorrhage (RH) and whether this incidence could be reduced by electronic monitoring of delivery. To assess the prognostic value of neonatal RH for future development of the child, the physical, motor, and psychologic states of 252 infants were examined 6 to 18 months following delivery. The incidence of RH was 37.3% and was not influenced by maternal age, parity, gestational age, course of pregnancy, birth weight, or electronic monitoring of delivery. The mode of delivery did influence the incidence of RH. Gesell developmental schedule showed no correlation between ocular findings and later development of the child.

Electrical accidents during pregnancy.

Electrical accidents during pregnancy are relatively infrequent, and reports are rare. Six pregnant women who suffered an electrical injury during pregnancy are presented here. For all, the current path through the body was from hand to foot. Changes that occurred in fetal movements and development as well as the outcome of the pregnancies, are presented. After delivery, the placenta and cord were carefully examined in all cases. From an analysis of the published cases and the present findings, it seems that there are no specific clinical and pathological signs of fetoplacental damage. Medical examination, shortly after the accident, may reveal a dead fetus. However, when it is found alive, oligohydramnios or growth retardation may develop later, and a close follow-up seems advisable. Pregnant women should be warned to notify their attending physician in all cases of electrical shock, no matter how apparently minor.

Uriscreen, a rapid enzymatic urine screening test: useful predictor of significant bacteriuria in pregnancy.

OBJECTIVE: To establish the reliability of a new rapid enzymatic screening test, the Uriscreen, in the detection of significant bacteriuria in pregnancy. METHODS: During a 6-month period, from July 1 to December 30, 1993, 313 consecutive pregnant patients were evaluated. Randomly voided, midstream, clean-catch urine specimens were used. Each sample was tested by routine laboratory culture and four rapid screening tests: the nitrite and leukocyte esterase dipstick, microscopic examination for pyuria, and the Uriscreen test. Results of the four rapid tests were compared with those of the urine culture. RESULTS: Twenty-four women (7.6%) had urine culture results indicating significant bacteriuria. The sensitivity of the nitrite test, the leukocyte esterase test, and a microscopic examination for pyuria was low (37, 52, and 56%, respectively). The Uriscreen test showed very high sensitivity (100%), lower specificity (81%), a high predictive value of negative results (100%), and a low positive predictive value (30%). CONCLUSIONS: The Uriscreen test is a reliable alternative to culture screening of all pregnant patients. A policy of performing a urine culture during pregnancy only on patients with a positive Uriscreen test will save as much as 80% of unnecessary cultures.

Recombinant technique and gonadotropins production: new era in reproductive medicine.

OBJECTIVE: To review current knowledge regarding recombinant DNA technology and its safety and efficacy in relation to recombinant gonadotropin production. DATA IDENTIFICATION AND SELECTION: Studies that relate specifically to recombinant DNA technology, method of laboratory production, and the clinical aspects of using recombinant gonadotropins were identified through literature and Medline searches. RESULTS: Recent developments in recombinant DNA technology have resulted in a rapidly expanding range of new diagnostic and therapeutic opportunities. This technology paves the way to the identification, isolation, cloning, and production of specific proteins. Recently, recombinant human gonadotropins became available for clinical use. The pharmacokinetics, receptor availability, pharmacodynamics, and safety were studied extensively and the drugs were found to be identical if not superior to urinary gonadotropins that have been used in reproductive medicine for the last 30 years. It is clear today that the use of recombinant human gonadotropins is expected to provide better batch-to-batch consistency, steady supply, and most importantly, a purified compound with high specific activity, which accounts for >99% of the preparation's protein content, allowing SC administration. CONCLUSION: There is no doubt that recombinant gonadotropins produced by genetic engineering technology are here to stay and will represent an important treatment modality in various fertility disturbances.

Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer.

From the reviewed data, it appears that CC, hMG-hCG, or the association of these drugs with IVF-ET and GIFT programs do not carry an increased risk for congenital malformations as a whole, nor is there any specific malformation that has an increased incidence or is related in any way with the use of these drugs. Table 7 represents the specific malformation rate per 1,000 births in the general population and in newborns delivered after treatment with CC, hMG-hCG, or IVF-ET and GIFT. The malformation rate in the treated groups does not differ from that of the general population. However, as shown by McIntosh et al., the incidence of congenital malformations often rises with a longer follow-up. Most of the reports about babies born after ovulation induction are based on the initial examination done shortly after birth. Thus, studies including examination of these infants up to at least 12 months of age will be undoubtedly of value. Also, data concerning the reproductive capability of women born after ovulation induction is lacking. With regard to the abortion rate in pregnancies achieved after such treatments and procedures, it can be concluded that it does not appear to be higher than that of the general population, particularly when early pregnancy loss, advanced maternal age, the infertility status, and the increased incidence of multiple pregnancies occurring in these patients are taken into consideration.

Comparison of sperm parameters, in vitro fertilization results, and subsequent pregnancy rates using sequential ejaculates, collected two hours apart, from oligoasthenozoospermic men.

OBJECTIVE: To evaluate the effect of second consecutive ejaculate collected 2 hours after the first one from infertile men on sperm quality and fertilization and pregnancy rates (PRs) in IVF. DESIGN: A prospective case-control study. SETTING: In vitro fertilization unit of a university hospital. PATIENTS: Thirty-nine consecutive infertile patients with oligoasthenozoospermia scheduled for IVF-ET. MAIN OUTCOME MEASURES: Two consecutive ejaculates were obtained 2 hours apart and were assessed for volume, sperm count, motility, morphology, and quality of swim-up fraction. The subsequent fertilization, cleavage, and PRs (as defined by the appearance of intrauterine gestational sac) were compared between the two ejaculates. RESULTS: In 28.2% of the individuals the semen analysis of the first ejaculate precluded proceeding with IVF. A statistically significant improvement was shown in sperm cell motility (31.9% +/- 20.7% versus 15.6% +/- 15.3%) and in motile count after swim-up (4.9 +/- 4.5 versus 2.6 +/- 3.1 x 10(6) sperm). No improvement could be demonstrated in sperm density or morphology. The volume of the second ejaculate was decreased significantly as compared with the first one. The fertilization rate, the cleavage rate, and PR were all increased when oocytes were exposed to sperm from the second ejaculate compared with oocytes exposed to sperm from the first ejaculate. The overall PR in our series was 25.6%. CONCLUSIONS: We suggest that in the group of infertile men with oligoasthenozoospermia, whose partners are scheduled for IVF-ET, if on the day of retrieved oocytes insemination, the ejaculate is of unacceptable quality, a second ejaculate collected 2 hours after collection of the initial ejaculate may produce a sample that exhibits improvements in both semen parameters and reproductive potential.

Antigenicity of sperm cells after freezing and thawing.

Freezing and thawing is thought to result in removal of spermatozoal membrane antigens. We investigated the presence of sperm antigens before and after freezing and thawing by means of the immunoperoxidase assay (IPAMA), sperm immobilization test (SIT), and separation of proteins by gel electrophoresis. The results of the IPAMA and SIT assays showed no difference in the membrane antigens before and after freezing and thawing. Analysis of surface proteins by gel electrophoresis demonstrated that freezing and thawing did not remove any particular group of proteins from the surface membrane of spermatozoa. According to the evidence of the three tests performed, there is no meaningful removal of antigens from the sperm cell surface membrane by the process of freezing, preservation, and thawing when carried out by the specific methods used. This work does not support the suggestion that in cases of immunologic incompatibility between spermatozoa and cervical mucus it would be possible to overcome the couple's infertility by employing the process of freezing, preservation, and thawing.

Luteinizing hormone: its role, mechanism of action, and detrimental effects when hypersecreted during the follicular phase.

OBJECTIVE: To review studies that have examined the role of LH, its mechanism of action, and its detrimental effects when hypersecreted during the follicular phase. DESIGN: Important published studies related to this topic were identified through a computerized bibliographic search. PATIENTS, PARTICIPANTS: Review of the need for LH during the follicular phase is based on animal models and women with hypogonadotropic hypogonadism. The association of hypersecretion of LH during the follicular phase with low rates of fertilization and high rates of pregnancy loss is based on clinical studies conducted in patients treated by IVF and ET and by induction of ovulation. The possible mechanism by which the effects occur is based on in vitro studies. RESULTS: The results of the studies cited in this review are consistent with the two-cell two-gonadotropin hypothesis implying that synergistic action of both FSH and LH is required for appropriate steroidogenesis. It also seems that, whatever the underlying mechanism, a raised serum LH concentration during the follicular phase confers a substantial risk of infertility and early pregnancy loss. CONCLUSION: By reviewing the literature it appears that LH exhibits an important role in the development of the growing follicle and maturation of the oocyte. It also seems that hypersecretion of LH during the follicular phase implies adverse effects on the fertility process. To further test this hypothesis, we now need systemic assessment of the methods of therapy used for treating patients with polycystic ovary syndrome, in relation to LH secretion and outcome of pregnancy.

Hormonal and clinical responses in amenorrhetic patients treated with gonadotropins and a nasal form of synthetic gonadotropin-releasing hormone.

Synthetic gonadotropin-releasing hormone (GnRH) in the form of nasal drops was self-administered by five amenorrheic patients in an attempt to assess its therapeutic value in anovulatory infertility. After follicular maturation had been induced with human menopausal gonadotropins (HMG), a total daily dose of 7.5 mg of GnRH in the form of nasal drops was self-administered at 2-hour intervals for 6 hours on 3 consecutive days. In four patients, plasma luteinizing hormone (LH) levels were significantly elevated over a period of at least 8 hours. In three of these patients, in addition, there was a definite upward shift in the basal body temperature (BBT) curve, and uterine bleeding occurred 6 to 9 days after the first dose of GnRH. In the fourth patient, ovulation was induced as indicated by a biphasic BBT curve, a plasma progesterone level of 13 ng/ml, and a luteal phase of 15 days. In the remaining patient, there was a borderline LH response and no clinical response. It is concluded that GnRH, in the form of nasal drops, is effective in eliciting and maintaining elevated plasma LH levels in patients in whom follicular maturation has been induced with HMG. By obtaining ovulatory LH levels, such a regimen can lead to ovulation. In addition, intranasal self-administration of GnRH is convenient and may provide an alternative route of administration for long-term therapy with this hormone.

Polyzoospermia: a definite pathologic entity.

Polyzoospermia has been repeatedly associated with reduced fertility and increased rates of spontaneous abortion. We examined semen samples of 1374 infertile men and found an incidence of 4.2% of semen with a sperm density exceeding 250 X 10(6) sperm cells/ml. The spontaneous pregnancy rate in 30 evaluated couples in whom the male partner presented with polyzoospermia was 38.7% and the spontaneous abortion rate was 25%. Sperm penetration tests revealed normal mucus-penetrating ability in 29 of 30 men examined. The reason for reduced reproductive performance in polyzoospermic men does not seem to be disturbed sperm mucus interaction.

Sperm storage in the human cervix: a quantitative study.

Twenty-five women scheduled for hysterectomy for nonmalignant disease participated in the study. Sperm storage in endocervical crypts was examined in three groups of patients: nine women pretreated with estrogen and inseminated with normal semen, nine women pretreated with gestagen and inseminated with normal semen, and seven women pretreated with estrogen and inseminated with abnormal semen. The number of crypts containing spermatozoa (colonized crypts) and the sperm density per crypt were examined in serially sectioned cervices. In estrogen-pretreated cervices both the percentage of colonized crypts and the sperm density were significantly higher than in gestagen-pretreated cervices. Large and giant crypts proved to be the main storage facility for spermatozoa. The localization of crypts along the endocervical canal did not influence sperm storage. The quality of semen appeared to be of critical importance to sperm storage. The percentage of colonized crypts and sperm density were severly reduced in patients inseminated with abnormal semen.

PIP: This study investigated whether estrogen and gestagen influence the capacity pattern and retention time of sperms in endocervical crypts, determined whether the mean number of sperms in the lower part of the cervix was similar to or different from that in the upper part, and established whether the retention time of sperms in cervical crypts differed in the case of abnormal semen as compared with normal semen. 25 women, scheduled for hysterectomy for nonmalignant indications were studied. 3 groups of patients were studied for sperm storage measurements: 9 women were pretreated with estrogen and inseminated with normal semen; 9 women were pretreated with gestagen and inseminated with normal semen; and 7 women were pretreated with estrogen and inseminated with abnormal semen. Serially sectioned cervixes were studied to quantitate the number of crypts containing sperm (colonized crypts). In estrogen-pretreated subjects, the percents colonized crypts and sperm density were significantly higher than in gestagen-pretreated subjects' cervixes. The main storage of sperm occurred in large and giant crypts. Localization of crypts along the endocervical canal had no influence on sperm storage. Semen quality was of critical importance in sperm storage; the percentages of colonized crypts and sperm density were severely reduced in subjects inseminated with abnormal semen.

Induction of follicular growth using recombinant human follicle-stimulating hormone in two volunteer women with hypogonadotropic hypogonadism.

OBJECTIVE: To examine the safety, tolerance, pharmacokinetics, follicular growth, and steroidogenesis after the administration of recombinant human FSH (Org 32489; Organon International, Oss, The Netherlands) in women with isolated hypogonadotropic hypogonadism. DESIGN: An open phase I multiple rising dose study with recombinant FSH in two hypogonadotropic but otherwise healthy women. The drug was administered intramuscularly one time per day for a maximum of 21 days, i.e., 75 IU for the first 7 days, 150 IU for the next 7 days, and 225 IU during the last 7 days. Treatment was discontinued if serum E2 was > or = 1,100 pmol/L and/or one or more growing follicle > 14 mm in diameter was observed. After the last recombinant FSH injection, subjects were monitored for another 3 weeks. SETTING: Specialist Reproductive Endocrinology and Infertility Unit. VOLUNTEERS: Two women with isolated hypogonadotropic hypogonadism who did not want to get pregnant anymore. MAIN OUTCOME MEASURES: Serum FSH, androstenedione (A), T, P, LH, follicular growth, and endometrial thickness. Safety parameters: blood pressure, heart rate, urinalysis, hematology, blood biochemistry, and antirecombinant FSH antibodies. RESULTS: Treatment with recombinant FSH resulted in dose-related increases of serum FSH. Both women showed follicular growth (diameter, 17 mm), whereas serum A concentrations were very low, and serum E2 concentrations rose to only 76.7 and 139.5 pmol/L, respectively. No antirecombinant FSH antibody formation or changes of safety variables were noted. CONCLUSION: This study in two women with hypogonadotropic hypogonadism is consistent with the two-cell theory that FSH alone can induce follicular growth. The low concentrations of A and E2 indicate the need for LH to induce appropriate steroidogenesis. It was also found that recombinant FSH is well absorbed, safe, and well tolerated after daily treatment for up to 21 days.

Intravenous albumin for the prevention of severe ovarian hyperstimulation syndrome in an in vitro fertilization program: a prospective, randomized, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of i.v. administration of human albumin solution for the prevention of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: A prospective, randomized, placebo-controlled study comparing the effects of i.v. administration of human albumin solution versus sodium chloride 0.9% solution at the time of oocyte retrieval with patients undergoing IVF-ET who are at high risk for the development of severe OHSS. SETTING: Specialized assisted reproduction unit. PATIENTS: Thirty-one patients undergoing IVF-ET who had serum E2 levels of 1,906 pg/mL (> 7,000 pmol/L) and multiple follicular development on the day of hCG administration. INTERVENTIONS: After hCG administration, patients were randomized to receive i.v., either 50 g of human albumin diluted in 500 mL of sodium chloride 0.9% or 500 mL of sodium chloride 0.9% at the time of oocyte retrieval. MAIN OUTCOME MEASURES: Ovarian size as measured by pelvic ultrasonography, development of ascites, serum E2 concentrations during the luteal phase, and results of the IVF-ET cycles. RESULTS: Although no patient who had received human albumin solution developed severe OHSS, there were four such cases in the control group. All four were hospitalized with marked ascites and ovarian enlargement. There were no significant differences between the two groups comparing serum E2 levels on the day of hCG administration and during the luteal phase, the number of oocytes retrieved, fertilization, and pregnancy rates. CONCLUSIONS: Our preliminary results suggest that the administration of human albumin solution may help to prevent the development of severe OHSS in high-risk patients. Further research is needed to assess the potential of this novel approach.

Can premature luteinization in superovulation protocols be prevented by aspiration of an ill-timed leading follicle?

In 12 patients stimulated for in vitro fertilization and embryo transfer (IVF-ET), a single leading follicle developed, whereas the other follicles were 6 mm smaller. In 7 patients chosen at random (group A), the leading follicle was aspirated, whereas in the other 5 the leading follicle was allowed to continue growing (group B). Comparison of the hormonal pattern of both groups showed that a premature luteinizing hormone (LH) surge was avoided only in group A, and only in this group a second follicle aspiration for IVF-ET was done, and two pregnancies were achieved. In group B, aspiration for IVF-ET was canceled because of premature LH surge. It is suggested that aspiration of a single leading follicle during ovulation induction may be an efficient method to avoid premature LH surge enabling other follicles to develop up to the preovulatory stage.

The luteinizing hormone surge--the final stage in ovulation induction: modern aspects of ovulation triggering.

OBJECTIVE: To compile updated information regarding gonadotropin secretion, specifically the physiology of the midcycle LH surge, in natural cycles and under various ovulation induction protocols. DATA IDENTIFICATION AND SELECTION: Studies that deal with the clinical aspects of LH surge manipulation or substitution were identified through literature and Medline searches. RESULTS: Three major regulatory factors have been identified as participants in the induction of the midcycle gonadotropin surge. These are hypothalamic GnRH secretion, ovarian and adrenal steroids, and less well-characterized ovarian peptide hormones. Gonadotropin-releasing hormone pulsatility is regulated by a complex mechanism that integrates multiple neurotransmitters and sex steroids. Estradiol plays a central role in the pituitary secretion of LH, which also is influenced by P concentrations. Gonadotropin surge attenuating factor also has been implicated in the regulation of timing and amplitude of the LH surge. Human chorionic gonadotropin is used extensively as a LH surrogate, but its use is associated with a number of disadvantages. Induction of an endogenous LH surge through use of the flare effect of GnRH analogues has been examined more recently and has been found to have several advantages. Recombinant human LH is in the final stages of clinical testing. CONCLUSION: Although much is known about the physiology of the midcycle LH surge and its variations under different clinical conditions, new approaches to the induction or substitution of the LH surge currently are being examined and learned. The introduction of recombinant gonadotropins into clinical practice is likely to influence ovulation induction and IVF practice to a significant degree in the near future.

The effect of estrogen and gestagen on the mucus production of human endocervical cells: a histochemical study.

The effect of hormonal stimulation on the intracellular mucus production of the endocervical cells was histochemically and morphometrically investigated. Twenty-seven cervixes from patients who had received estrogen or gestagen prior to hysterectomy were examined. "Upper" versus "lower" cervix and "small" versus "large" crypts were compared in both groups of patients. The histochemical analysis of mucins within the cells was based mainly on the combined alcian blue/periodic acid Schiff (AB/PAS) techniques at various pH levels. A semiquantitative estimation using cell counts and statistical evaluations was done for each staining method. The results indicate that sex hormones influence the chemical composition of endocervical mucus production. In addition, the nature of the intracellular mucus varies with the cryptal size and location within the cervical canal.

The hypothalamus as a regulator of reproductive function.

In this review of the role of the hypothalamus as a regulator of reproductive function we have presented a short history of the important anatomical and physiological findings, the structure and properties of gonadotrophin releasing hormone and its function and mode of action in the reproductive process. The latest clinical studies have been presented and we have discussed the therapeutic and diagnostic applications of GnRH. Although the progress in the last few years has been relatively enormous, research on the physiological and clinical implications of these discoveries has probably only now reached its peak and it was thus felt that the time was ripe to write this summary.

Midtrimester induction of abortion: comparison of extraovular prostaglandin E2 and intra-amniotic prostaglandin F2 alpha.

The efficacy of extraovular prostaglandin E2 and intra-amniotic prostaglandin F2 alpha for pregnancy termination in midtrimester was compared. A retrospective review of pregnancy termination in midtrimester using intra-amniotic instillation of 40 mg of prostaglandin F2 alpha (n = 133) or extraovular instillation of prostaglandin E2 at a rate of 500 micrograms/hour (n = 81) was performed. Both groups had a similar mean induction-to-abortion interval (19.5 +/- 19.9 and 20.9 +/- 18.2 hours for extraovular PGE2 and intra-amniotic PGF2 alpha, respectively) and a similar success rate of abortion within the first 24 hours of initial treatment (84.0% for extraovular PGE2 and 76.7% for intra-amniotic PGF2 alpha). The two groups had a similar and low (9.8%) incidence of complications. It is concluded that either of the methods used in the study (i.e. extraovular PGE2 or intra-amniotic PGF2 alpha) can be used safely and effectively for pregnancy termination in midtrimester.

PIP: A comparison was made of midtrimester induction of abortion by extraocular prostaglandin E2 (PGE2) and intraamniotic prostaglandin F2alpha (Pgf2alpha) in a recent series of patients at Kaplan Hospital, Rehovot, Israel. Pgf2alpha 40 mg was instilled intraamniotically in 133 women from July 1988-December 1990. PGE2 was instilled at 500 mcg/hour in 81 women treated from January 1991-June 1992. The abortion interval was 20.9 hours for Pgf2alpha and 19.5 hours for PGE2. 76.7% of women given Pgf2alpha and 84% of those given PGE2 aborted within 24 hours. If abortion did not occur within 24 hours, oxytocin or a repeat dose of Pgf2alpha was administered. Complication rates were 3.7 and 2.5% for hemorrhage requiring transfusion, 3.0 and 3.7% fever for 2 days, 0.7 and 1.2% for PG side effects, and 2.2 and 1.2% for curettage, with - Pgf2alpha and PGE2, respectively. One woman given PGE2 extraamniotically fibroids. In contrast with comparative studies of these 2 methods published in the 1970s, where extraamniotic PGE2 often produced more infection and intraamniotic Pgf2alpha often caused gastrointestinal side effects, this study found comparable complication rates for the 2 methods.