Laparoscopic ligation of the umbilical cord of an acardiac fetus.

We performed umbilical cord ligation using laparoscopic technique in twins with twin reversed arterial perfusion sequence.

Eliminating the risk of life-endangering complications following overstimulation with menotropin fertility agents: a report on women undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: To evaluate a new method for preventing the life-endangering complications associated with inadvertent menotropin-induced severe ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer (IVF-ET). METHODS: Seventeen women each underwent a single cycle of controlled ovarian hyperstimulation with menotropins in preparation for IVF-ET. The indications for IVF-ET were tubal occlusion in nine, endometriosis in six, and unexplained infertility in two. The peak plasma estradiol (E2) concentration before hCG administration was greater than 6000 pg/mL and more than 30 ovarian follicles were detected by transvaginal ultrasound. Thus, life-endangering complications associated with severe ovarian hyperstimulation syndrome were highly likely to occur following hCG administration. Rather than cancel the cycle of treatment, menotropin therapy was discontinued and hCG administration was deferred for a number of days until the plasma E2 concentration fell below 3000 pg/mL ("prolonged coasting"), whereupon hCG was administered and egg retrievals and ETs were duly performed. RESULTS: None of the women developed severe ovarian hyperstimulation syndrome. There were six viable pregnancies (35.2%), which proceeded normally. CONCLUSION: This study indicates that "prolonged coasting" prevents severe ovarian hyperstimulation syndrome in severely overstimulated women undergoing IVF-ET, without necessitating cycle cancellation.

Management of suboptimal sonographic endometrial patterns in patients undergoing in-vitro fertilization and embryo transfer.

A total of 816 women who underwent 1332 cycles of ovarian stimulation for in-vitro fertilization and embryo transfer (IVF/ET) had sonographic assessments of the endometrium within 2 days of oocyte retrieval. Endometrial linings were classified on the basis of thickness and echogenicity, using a grading system described previously. Grades I and IIB ('poor') were associated with a 6% viable pregnancy rate (advanced beyond 12 weeks' gestation) compared with a 29% rate for Grade IIA ('optimal'). In a subset of 112 women with poor endometrial linings during natural cycles, eight out of 21 women (38%) under 40 years of age developed optimal linings following ovarian stimulation with menotrophins, while 19 out of 91 women (21%) aged 41-45 years converted to optimal linings. Twenty-two out of 47 women (44%) who failed to develop optimal endometrial linings following ovarian stimulation converted to Grade IIA during subsequent cycles of exogenous oestrogen replacement. The financial, emotional, and physical burden associated with IVF/ET demands that patients with poor endometrial linings following ovarian stimulation with menotrophins be counselled with regard to either cancelling their cycles of treatment, or having their embryos cryopreserved for transfer to the uterus during a subsequent hormonal replacement cycle.

Mock embryo transfer in early luteal phase, the cycle before in vitro fertilization and embryo transfer: a descriptive study.

OBJECTIVE: To investigate visually the uterine retention or sequestration of boluses of radiopaque dye, mimicking embryo transfer (ET). DESIGN: During the cycle before in vitro fertilization (IVF) and ET, patients underwent a mock ET of 40 microL of radiopaque dye into the uterine cavity. The patient was positioned supine for retroverted or axial and knee chest for anteverted uteri. The position of the dye at injection, during and after catheter removal, and during patient roll over and standing was monitored. SETTING: Treatment of infertility in a private practice. PATIENTS: Thirty-four IVF patients. INTERVENTIONS: During the cycle before IVF/ET, patients underwent a mock ET using a bolus of 40 microL of radiopaque dye. MAIN OUTCOME MEASURES: Planned before visual observation began. RESULTS: The dye remained primarily in the uterine cavity in only 68% (optimum ET position is knee chest for anteverted and supine for retroverted or axial uterus) and 48% (nonoptimum position is supine for anteverted uterus) at mock ET; in those groups, a 33% clinical pregnancy rate (PR) per retrieval resulted. Dye motility into the fallopian tube(s), cervix, and/or vagina is 38.2%, 8.8%, and 11.8%, respectively. CONCLUSIONS: If the mock ET had been the actual ET, 32% (optimum ET position) and 52% (nonoptimum ET position) of all patients would have lost their opportunity for pregnancy as a result of the ET procedure. Our 33% PR per retrieval among those patients who retained the dye in utero is more consistent with our expectations, given the advanced technologies of IVF/ET today.

In vitro fertilization (IVF) of mouse ova in HEPES-buffered culture media.

Some major drawbacks of a bicarbonate-buffered culture medium include the requirement of an elaborate incubator system able to maintain a 5% CO2 environment and the inability of the culture medium to maintain a physiological pH range (pH 7.3-7.4) in room air (0.03% CO2). This work resulted in the development of IVF culture media, BB (modified T6) and Hams-HEPES, which use HEPES-buffered systems not requiring the specialized CO2 environment to maintain a physiological pH range in room air. These media generate above-average cleavage rates in in vitro fertilized, superovulated B6CBAF1 mice ova. The effect of heparin and HEPES on cleavage was studied and neither had a significant effect at the concentrations used. Cleavage rates of nonfertilized ova (parthenogenic division) were 9 to 13%. There was no significant difference in parthenogenesis between any of the culture media and it appears to be a function of the strain of mice and the timing between human chorionic gonadotropin (hCG) injection and ovum collection. These results emphasize the need to account for parthenogenesis when determining cleavage rates of in vitro fertilized mouse ova. Also, the results suggest that because of individual mouse differences in cleavage rates, it is important to use an adequate number of mice per group to determine an accurate, average cleavage rate.

In vitro fertilization and embryo transfer: two-year experience.

Between February 1983 and January 1985, 206 laparoscopies were performed on 172 women following controlled ovarian hyperstimulation with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Sixty-four clinical pregnancies advanced beyond the sixth week of gestation and were confirmed by ultrasound; and 37.2% of the patients conceived after in vitro fertilization and embryo transfer. The clinical pregnancy rate was 31.1% when based on the number of laparoscopies performed and 33.9% when based on the number of embryo transfers. There were 12 multiple pregnancies (18.8%), 11 miscarriages (17.2%), and one ectopic (tubal) pregnancy (1.6%). The most important factors contributing toward the success of this program were the establishment of specific criteria for patient selection, rigid adherence to clinical and laboratory protocols, and the maintenance of strict quality control.

The development of a successful non-university-based ambulatory in vitro fertilization/embryo transfer program: phase I.

Most of the current in vitro fertilization and embryo transfer (IVF-ET) programs are university-based. The establishment of a successful ambulatory IVF program in association with a busy, two-man general obstetrics-gynecologic practice is described. Seventy-one infertile couples were screened between February 1 and October 15, 1983. Forty-three couples were judged eligible for IVF-ET. Forty-three women underwent a single attempt at ET. The first 13 of these women underwent controlled ovarian hyperstimulation (COH) with 150 mg clomiphene citrate and human chorionic gonadotropin (hCG), and the remaining 30 underwent COH with human menopausal gonadotropin (hMG) and hCG. One of the 13 patients who underwent COH with clomiphene citrate conceived but subsequently miscarried early in the first trimester, for an 8% pregnancy rate. There were 12 pregnancies among the 30 patients who received hMG and hCG, for a 40% pregnancy rate. Only three of these pregnancies miscarried in the early first trimester, and three of the nine viable pregnancies are twin gestations. The possible factors responsible for the high pregnancy rate with IVF-ET, using COH with hMG and hCG, are discussed, and the feasibility of its performance in a well-controlled, non-university program is demonstrated.

In vitro sperm capacitation and transcervical intrauterine insemination for the treatment of refractory infertility: phase I.

Fourteen couples with long-standing infertility, associated with cervical mucus insufficiency, male subfertility, or unexplained infertility, participated in a therapeutic trial. The female partners, who were all ovulatory, were given human menopausal gonadotropin from day 2 of the menstrual cycle (controlled ovarian hyperstimulation). When plasma estradiol concentrations reached 1000 to 2000 pg/ml, human chorionic gonadotropin was given. Approximately 32 hours and again 70 hours thereafter, a masturbation specimen of the husband's sperm was capacitated in vitro and inseminated transcervically into the uterine cavity. Five women (35%) conceived following a single cycle of treatment. Four of the pregnancies are currently progressing normally; one ended in a spontaneous miscarriage in the early first trimester. The potential role of in vitro sperm capacitation and transcervical intrauterine insemination in the treatment of refractory infertility unrelated to female organic pelvic disease is discussed.

Assaying plasma prekallikrein (PPK) by a chromogenic based method: analytical considerations and reference values in healthy adults, the pregnant woman, and the neonate.

Analytical assays that measure the amidolytic activity of plasma kallikrein (PK) must overcome the problem of anti-kallikrein inhibition during the activation of PPK to PK. We resolved this problem by exposure of plasma to 50 mg/L dextran sulfate in acetone/water (35/65, vol/vol) at 0 degrees C for 15 minutes. PK activity was assayed using the chromogenic substrate, S-2302 (KABI). A centrifugal analyzer (CentrifiChem) was used to monitor the change in absorbance at 405 nm and 37 degrees C. The assay was linear to a value 3 times that found in normal human plasma. The specificity of the substrate for PK was demonstrated by using plasma deficient in PPK (Fletcher trait) diluted with normal human pooled plasma (NHPP). Day-to-day analytical variation was 2.4% for NHPP having a mean value of 85.9 mukat/L (n = 26). Using our amidolytic method, we determined PPK values in 50 healthy adults, 80 pregnant women during each trimester of gestation, and 151 neonates (cord blood specimens). The middle 95% reference interval for the adults was 54.0 - 118.8 mukat/L, for pregnant women at first trimester: 59.0 - 129.0, second trimester: 72.3 - 161.5, third trimester: 75.6 - 152.4, day of labor: 67.7 - 144.9, and 1-9 weeks postpartum: 69.4 - 151.0 mukat/L, and for the neonate: 11.5 - 44.9 mukat/L. We observed that women on oral contraceptives had significantly greater PPK values than those not on oral contraceptives. Intra-individual variation of PPK values was relatively low in non-pregnant women with the day-to-day coefficient of variation being 4.1 - 6.1% in 5 subjects monitored over a 30 day period. The high value of inter-individual/intra-individual ratio was appreciated in pregnant women in that the PPK value observed during the first trimester was a means to predict the value approaching term. The mean PPK value during the first trimester was 105.1% of the mean seen in non-pregnant women while the mean PPK value nearing term was 130.1% of that value.

Identifying the small-for-gestational-age fetus on the basis of enhanced surfactant production.

The clinical utility of concurrent measurements of the fetal biparietal diameter, as measured by ultrasonography and fetal pulmonary maturity, as assessed by the amniotic fluid consisted of 57 cases in which pregnancy produced a low birth weight neonate (less than 2500 g). The combination of a small fetal biparietal diameter (less than 8.5 cm) and a mature foam stability index value (0.47 or greater) was associated with small-for-gestational-age neonates in 16 of 19 cases. In addition, the occurrence of an immature foam stability index value (less than 0.47) and a fetal biparietal diameter of less than 8.5 cm was associated with appropriate-for-gestational-age newborns in 16 of 16 cases. The discriminating ability of the foam stability index test in identifying the small-for-gestational-age infant was lost when the fetal biparietal diameter was 8.5 cm or more. Of clinical note was the fact that 14 cases in which the neonatal respiratory distress syndrome occurred were all associated with appropriate-for-gestational-age infants and foam stability index values of less than 0.47 (ie, immature). The results of this study suggest a potentially important clinical role for the concurrent measurement of fetal biparietal diameter and performance of the amniotic fluid foam stability index test in the prenatal evaluation of the high-risk, small, third-trimester fetus.

The major determinants of perinatal mortality in a large metropolitan hospital. Results of a retrospective study.

We reviewed the records of all perinatal deaths that occurred at Mount Sinai Hospital, New York, from 1975 to 1978. The perinatal mortality rate was 20 per 1,000 births. Most potentially preventable perinatal deaths occurred in association with low birth weight. We noted that fetal deaths that occurred prior to the onset of labor were usually associated with small-for-gestational-age (SGA) or growth-retarded fetuses, whereas deaths occurring during labor were usually the result of trauma to the very small third-trimester fetus, one weighing less than 1,500 gm. Neonatal deaths most commonly resulted from prematurity-related complications (mainly the idiopathic respiratory distress syndrome) in appropriately grown, very-low-birth-weight fetuses, those weighing less then 1,500 gm at birth.

Diagnostic reliability of the lecithin/sphingomyelin ratio assay and the quantitative foam stability index test: results of a comparative study.

We analyzed 331 pregnancies where clear, uncontaminated amniotic fluid was obtained within 72 hours of delivery from both normal and complicated gestations. There were 43 cases of the neonatal idiopathic respiratory distress syndrome (IRDS), 42 of which were associated with foam stability index (FSI) values of less than 0.47. In 276 of the 323 cases sufficient amniotic fluid was available to permit concurrent performance of the lecithin/sphingomyelin ratio (L/S) assay. Thirty-five cases of IRDS occurred in this group, 8 of which were associated with L/S ratio values greater than 2.0. The risk of IRDS occurrence was calculated for three groups of FSI values (shown in parentheses below). They were as follows: group I--FSI values less than or equal to 0.43 (73%); group II--FSI values of 0.44 to 0.46 (29.2%); group III--FSI values greater than or equal to 0.47 (0.35%). Comparable evaluations for the L/S ratio procedure showed the FSI test to be significantly more specific and sensitive than the L/S ratio assay. The improved performance of the FSI test was most marked in pregnancies complicated by insulin-dependent diabetes mellitus and intrauterine growth retardation. The low cost, ease and rapidity of the FSI test, as well as the fact that it does not require sophisticated technical equipment or expertise, makes this sensitive and specific assay a method of choice for the prenatal evaluation of fetal pulmonary maturity.

Evaluation of the small third-trimester fetus using the foam stability index test.

The diagnostic effectiveness of the lecithin:sphingomyelin (L:S) ratio was compared with that of the quantitative amniotic fluid foam stability index (FSI) test in the prenatal evaluation of pregnancies associated with fetuses appropriately grown for gestational age (AGA) and with intrauterine growth retardation (IUGR). In 27 such pregnancies, both the L:S ratio assay and the FSI test were performed on amniotic fluid specimens collected within 72 hours of delivery. Of the 27 low birth weight (LBW) neonates studied, 15 were small for gestational age (SGA) but did not have idiopathic respiratory distress syndrome (IRDS), whereas of 12 AGA neonates, 9 had IRDS. The 15 IUGR cases were characterized by FSI values varying from 0.47 to 0.55, whereas the 12 AGA cases had values varying from 0.42 to 0.48. Thus, the FSI showed excellent differentiation between these 2 entities. The L:S ratio ranged from 1.1 to 3.4 in cases associated with IUGR and from 1.0 to 2.4 in AGA cases, showing a high degree of overlap. The combination of an L:S ratio of less than 1.5 and an FSI value of less than 0.47 consistently identified the fetus who would have IRDS.

Rheumatic heart disease diagnosed during pregnancy: a 30-year follow-up.

One hundred one patients originally diagnosed as having rheumatic heart disease (RHD) during the years 1945-1948 were reevaluated in 1975 to determine the natural history of the disease. Twenty patients (19.8%) showed no sign of RHD. Of the patients with confirmed RHD, 56 (70.0%) had their original lesion confirmed, while 23 (28.8%) had developed additional valvular involvement. Pure mitral stenosis resulted in significantly lower mortality than all other valvular lesions, and congestive heart failure was the leading cause of death. Nineteen patients underwent cardiac surgery; the mortality in this group (52.6%) was not significantly higher than that in the overall RHD group (38.8%). False diagnosis of RHD during pregnancy is common. A more thorough evaluation of the "cardiac murmur of pregnancy" is advocated.

Primary adenocarcinoma of the vulva originating in misplaced cloacal tissue.

Primary adenocarcinomas of the vulva are rare tumors and usually arise from the Bartholin's gland. However, other potential sources of adenocarcinoma exist. A case is reported where it is believed that the source of the primary adenocarcinoma was a misplaced cloacal remnant. The method of treatment was by radical surgery and the prognosis is uncertain.

Colposcopy and selective biopsy in patients with abnormal cervical cytology.

Patients with atypical or positive findings on cervical cytology should be referred to a special colposcopy clinic as the next step in investigation. Colposcopy complements cytology, and when combined with selective biopsy of the worst-affected area allows a high level of diagnostic accuracy (90,7%). The necessity for diagnostic conization with its risks is markedly reduced. When all three modalities were used in combination, only 0,7% of invasive cancers were missed.

Complications and outcome of induced labour.

One thousand and twenty-two induced labours are reviewed retrospectively. The incidence of induction of labour differed significantly in the various ethnic groups. Hypertension was the major indication and labour was successfully induced in 95,4% of patients. One-fifth of induced labours ended in caesarean section. The major complications associated with induction, fetal distress, cephalopelvic disproportion and hypertonic uterine inertia, and preventable. The perinatal loss associated with induction is mainly due to factors not related to induction per se.

Perinatal mortality in Cape Town.

Perinatal mortality in Cape Town has progressively decreased in all racial groups over the past 60 years. The perinatal mortality rate for Coloureds and Blacks, however, remains at 20 per 1 000 more than for Whites. While the stillbirth rate approximates the early neonatal death rate in Whites, the stillbirth rate for Coloureds and Blacks is double the rate for early neonatal deaths. Although there is a significantly higher early neonatal death rate for Coloureds and Blacks, the major component of perinatal loss is stillbirth and 80% of stillbirths occur before the onset of labour. Focus should be on the detection of the fetus at risk, with, perhaps, earlier intervention.