Use of time to event analysis to estimate the normal duration of human pregnancy.

BACKGROUND: Current estimates of the average duration of human pregnancy are flawed by inaccurate estimation of the time of conception and by failure to account adequately for the effect of routine elective delivery post-term. METHODS: In this study, 1514 healthy pregnant women were studied in whom the discrepancy between the menstrual history and first trimester crown-rump length estimated gestational age was within -1 to +1 day difference. The duration of gestation was estimated using time to event analysis: non-elective delivery was taken to be the event, and elective delivery was taken to be censoring. RESULTS: The median time to non-elective delivery using the Kaplan-Meier product limit estimate was 283 days after last menstrual period (LMP) and there was no difference comparing male and female fetuses. The median was significantly greater for nulliparous women compared with multiparous women (284 versus 282 days, P < 0.0001). Multivariate analysis using Cox's proportional hazards model confirmed the independent effect of nulliparity on duration of pregnancy [hazard ratio, 0.75; 95% confidence interval (CI) 0.67-0.85] and demonstrated no effect of maternal age, previous abortions, fetal sex, high parity, or bleeding before 24 completed weeks of gestation. Bleeding in the third trimester of pregnancy was, however, associated with an earlier onset of spontaneous labour (hazard ratio, 1.38; 95% CI 1.03-1.84). CONCLUSION: This study provides a basis for predicting the probability of labour at a given gestational age at term.     

Factors affecting time to pregnancy

BACKGROUND: Both lifestyle factors and occupational and environmental factors have been suggested to affect the female reproductive system. In the present study, the separate and joint effects of several such factors are investigated. METHODS: Information on time to pregnancy (TTP) was available for 1578 women randomly selected from the general Swedish population. The information was collected retrospectively by using self-administered questionnaires. By means of logistic regression of survival data, fecundability odds ratios were determined for many factors. Multivariate models were used to determine which factors had the most impact on TTP. RESULTS: Several lifestyle factors were found to associate with TTP. However, only use of oral contraceptives prior to attempting to conceive, menstrual cycle length, age at conception and parity remained in the multivariate models. Together, these factors explained 14% of the variance in TTP. Excluding first and second month conceptions, only age at conception and menstrual cycle length remained in the multivariate models, together explaining only 8% of the variance in TTP. CONCLUSIONS: Although information on several factors was available, the multivariate model explained only a small fraction of the variation in the observed time to pregnancies. Furthermore, female biological factors seemed more important predictors of TTP than lifestyle factors.     

Feasibility of surveillance of changes in human fertility and semen quality

There is concern that male fertility is declining, but this is difficult to study because few men volunteer for studies of semen quality, and recruitment bias may over-represent the subfertile. The Human Reproduction Programme of the World Health Organization developed a protocol for multicentre studies of fertility involving a questionnaire for pregnant women to obtain time to pregnancy (TTP): the number of menstrual cycles taken to conceive. Male characteristics and semen quality will be determined in a subset of the partners. Our aim was to validate the TTP questionnaire, and to examine potential recruitment bias and feasibility of conducting large-scale surveillance of fertility. The questionnaire was administered to 120 pregnant women (16-32 weeks). Validation included internal reliability by consistency of responses, test-re-test reliability by repeat administration (20 women) and accuracy by comparison of gestational age from first antenatal ultrasound and menstrual dates. Internal reliability was high. Agreement between categorical responses on re-testing was very good (k > 0.8). In both the re-test and gestational age analysis, differences in TTP of 1 cycle were found (standard deviation <0.25 cycles). In this small pilot study there was no evidence of recruitment bias. Response rates indicate the feasibility of surveillance of fertility in large maternity centres.     

Comparison of fetal growth in singleton, twin, and triplet pregnancies.

The objective of this longitudinal retrospective study was to evaluate differences of the fetal growth and fetal organ growth among singleton small for gestational age (S-SGA), singleton appropriate for gestational age (S-AGA), twin (Tw-AGA), and triplet (Tri-AGA) infants. Ultrasonographic examinations were performed on 35 S-AGA, 18 S-SGA, 52 Tw-AGA and 12 Tri-AGA fetuses. Circumferences of head (HC), abdomen (AC), spleen (SC) and adrenal gland (AGC) and lengths of femur diaphysis (FDL), liver (LL), estimated weight (EWT) were measured every 2 weeks after 15 weeks of menstrual age until delivery. There was no significant difference in predicted HC values in S-AGA, Tw-AGA and Tri-AGA fetuses; these values were lowest in S-SGA fetuses. As the number of fetuses in the uterus increased with advancing menstrual age, the slope of the growth curve for predicted AC value became lower, but there was no significant difference between Tri-AGA and S-SGA fetuses. There was no significant difference in predicted FDL values among Tw-AGA, Tri-AGA and S-SGA fetuses; those values were significantly lower than that in S-AGA fetuses. There was no significant difference in predicted EWT value between Tw-AGA and Tri-AGA fetuses, which were intermediate between those for S-AGA and S-SGA fetuses. There were no significant differences in predicted SC and AGC values between S-AGA and Tw-AGA fetuses, respectively. However, in S-SGA fetuses, the slopes of the growth curve for SC and AGC were lower than those in the other two groups with advancing menstrual age. There were slight differences in predicted LL values between S-AGA, S-SGA and Tw-AGA fetuses. These results suggest that in AGA fetuses, there was a slight difference in growth pattern among singleton, twin, and triplet pregnancies.     

Uterine artery Doppler velocimetry and the outcome of pregnancies resulting from ICSI.

BACKGROUND: An increased incidence of pregnancy complications following assisted reproduction has been reported. The use of uterine artery Doppler ultrasound may aid the prediction of such complications. METHODS: Doppler was performed at 18-24 weeks gestation in 114 singleton and 32 twin pregnancies after intracytoplasmic sperm injection (ICSI) and compared with a control group matched for age, parity and plurality. Outcome variables included gestational age at delivery, prematurity, preterm premature rupture of membrane (PPROM), birth weight, birth weight discordance of >20% in twins, small for gestational age (SGA), mode of delivery, development of pre-eclampsia and placental abruption. RESULTS: Compared with the controls, there were no significant differences concerning uterine Doppler parameters, pregnancy complications and the neonatal outcome, either in singleton or in twin pregnancies. According to Doppler results and/or risk factors by medical history, 42% of singleton ICSI and 39% of spontaneous singleton pregnancies were considered as high risk. In singletons, abnormal Doppler findings were associated with pre-eclampsia in 22% and SGA in 26% of ICSI patients, compared with 33 and 21% in controls; in contrast, 0 and 10% in ICSI and 3 and 6% in controls showed these complications but no risk factors respectively. No correlation was found between PPROM, prematurity, the rate of Caesarean section and pathological Doppler results. CONCLUSIONS: Uterine Doppler examination holds the potential to identify patients with an increased risk for developing pregnancy complications. According to our results, this risk is not elevated after ICSI treatment, therefore the decision of offering an intensified antenatal care should be based on the results of Doppler examination or risks by medical history rather than the mode of conception.     

Intrauterine sonographic measurement of embryonic brain vesicle

Our purpose was to evaluate embryonic brain vesicle measurements using intrauterine sonography in early first-trimester pregnancy. Fifty-one women about to undergo therapeutic abortion from 7-9.9 weeks gestational age were studied with a specially developed flexible catheter-based high-resolution real-time miniature (2.4 mm in outer diameter) ultrasound transducer (20 MHz). Length, width and height of telencephalon, diencephalon, mesencephalon and rhombencephalon were measured. The normal range of embryonic brain vesicle measurements for each day of pregnancy was determined. Curvilinear relationships were found between the menstrual age and telencephalon height (r(2) = 71.2%), diencephalon length (r(2) = 39. 6%), width (r(2) = 39.4%) and height (r(2) = 48.3%) and mesencephalon length (r(2) = 59.0%) respectively. Linear relationships were found between the menstrual age and telencephalon width (r(2) = 41.4%), mesencephalon height (r(2) = 58.7%) and rhombencephalon length (r(2) = 44.9%), width (r(2) = 56.8%) and height (r(2) = 35.5%) respectively. Telencephalon length and mesencephalon width were constant throughout menstrual age. These results suggest that intrauterine sonography provides accurate embryonic brain measurements in utero. Moreover, intrauterine sonography may become an important modality in future embryological research and in detection of embryonic brain developmental disorders in early first-trimester pregnancy.     

Endometriosis: Oestrogen and progesterone receptors in endometriotic tissue and endometrium: comparison of different cycle phases and ages

The levels of oestrogen and progesterone receptors were analysedin 62 endometriotic tissue samples obtained at laparotomy of58 women and in samples of endometrium obtained simultaneouslyfrom 49 of the women. Both ligand techniques and enzyme immunoassayswere used for the assays. The steroid receptor levels were significantlylower in endometriotic tissue than in endometrium, both in cytosoland nuclear fractions. The differences were most pronouncedin follicular phase. In endometrium the oestrogen and progesteronereceptor levels varied during the menstrual cycle, being highestin follicular phase. In endometriotic tissue, the oestrogenreceptor level remained low throughout the cycle. The progesteronereceptor level, determined by immunoassay, increased duringthe menstrual cycle, being higher in luteal than in follicularphase. This cycle phase pattern was found neither in the nuclearprogesterone receptor level nor when the cytosol was assayedwith the ligand technique. In contrast to endometrium, therewere no correlations between patients' age and steroid receptorlevels in endometriotic tissue. The results show that oestrogenand progesterone receptors in endometriotic tissue have a differentpattern during the menstrual cycle than endometrium and thatthe progesterone receptors synthesized are not all biologicallyactive. These results strengthen previous data indicating differencesin the hormonal regulation of the two tissue types.     

Non-genetic and non-gestational parenthood: consequences for parent-child relationships and the psychological well-being of mothers, fathers and children at age 3

BACKGROUND: Findings are presented of the third phase of a longitudinal study of children conceived by assisted reproduction procedures involving surrogacy and/or donor conception. METHODS: At the time of the child's third birthday, 34 surrogacy families, 41 donor insemination families and 41 oocyte donation families were compared with 67 natural conception families on standardized interview and questionnaire measures of the psychological well-being of the parents, mother-child relationships and the psychological well-being of the child. RESULTS: The differences found between family types reflected higher levels of warmth and interaction between mothers and their 3-year-old children in assisted reproduction families than in families with a naturally conceived child. A higher proportion of surrogacy parents than donor conception parents had told their children about the nature of their birth. CONCLUSIONS: It appears that the absence of a genetic and/or gestational link between parents and their child does not have a negative impact on parent-child relationships or the psychological well-being of mothers, fathers or children at age 3.     

Prognostic factors of reproductive outcome after myomectomy in infertile patients

The objective of this study was to identify the prognostic factors for conception after myomectomy carried out in cases of infertility. A total of 91 infertile patients presenting at least one subserous or intramural myoma measuring >2 cm underwent myomectomy. The characteristics of the patients, myomata and associated infertility factors were collected in a uniform and systematic way. A postal questionnaire was sent to patients. For each of the various factors studied, the specific cumulative probability of spontaneous intrauterine conception was estimated using the Kaplan-Meier method. Multiple regression analysis was then carried out using Cox's proportional hazards model. The cumulative probability of spontaneous intrauterine conception at 2 years follow-up was 44% (95% confidence interval: 32-56%). The cumulative probability of conception was less after removal of a posterior or intramural myoma, after a sutured hysterotomy, and when accompanied by a male factor, associated tubal or ovulation pathology. The cumulative probability of conception was greater after ablation of myomata responsible for menometrorrhagia. The size, deforming effect on the cavity and age played no role in our sample. Our results indirectly suggest that post myomectomy adhesions could have an adverse effect on fertility. Myomata responsible for menometrorrhagia are also the cause of infertility. In the presence of an associated male, tubal or ovulatory factor, the results were poor and it was not possible to determine if a myomectomy should be performed in these cases in order to enhance fertility.     

Oxygen consumption in normally grown, small-for-dates and large-for-dates new-born infants

1. Serial measurements of minimal oxygen consumption (V(O2)) have been obtained from nineteen healthy new-born infants in order to find out how body weight, gestational age and age after birth affected V(O2). The first measurement of V(O2) was done within 12 hr of birth, and further measurements were made at intervals until the baby left hospital.2. The majority of the infants (seventeen) weighed less than 2.5 kg at birth, and were ;premature' according to international definition. Gestational age, calculated from the mother's last menstrual period, was corroborated by clinical data and obstetrical history. The babies were divided into four groups according to birth weight and gestational age combined (see Table 1). Babies in the first two groups were the appropriate weight for dates (i.e. normally grown), babies in the other two groups were either small-for-dates or large-for-dates.3. At birth minimal V(O2) was closely correlated with birth weight in all babies and appeared to be directly proportional to it. The value for V(O2)/kg was similar in all groups. V(O2) was not related to gestational age per se. However, in the two normally grown groups V(O2) was roughly related to gestational age because birth weight was related to gestational age.4. In all babies minimal V(O2) rose progressively with increasing age after birth; a marked increase in V(O2) occured in the first week of life, despite a small decline in body weight.5. At a given age after birth differences in V(O2)/kg between the four groups were mostly less than 10%, and in general the differences were not statistically significant.Values for minimal V(O2) in all four groups were roughly:5 ml. O(2)/kg.min at < 12 hr of age.7 ml. O(2)/kg.min at 7-14 days of age.9 ml. O(3)/kg.min at about 2 months of age.6. It is concluded that:(a) At birth minimal V(O2) is largely determined by birth weight. V(O2)/kg is little affected by either rate of growth in utero or gestational age.(b) Minimal V(O2) is a function of age after birth as well as of body weight, and the value for V(O2)/kg increases as the baby gets older.     

Gestational Age Correlates With Immunosuppressive Properties of Hydatidiform Mole Pregnancies

PROBLEM: Soluble trophoblast extracts (HME) from some human hydatidiform mole pregnancies suppress IL-2-dependent T-cell proliferation, while others express no immunosuppressive bioactivity. This study was designed to determine if suppression by HME was correlated with gestational age, uterine size, or hCG secretion. METHOD: Soluble extracts were prepared from nine hydatidiform mole trophoblast samples and screened for immunosuppressive activity using a murine cytotoxic T-cell proliferation assay (CTLL-2). Gestational ages were determined from last menstrual cycle and uterine size was estimated at the time of surgery. Serum samples were collected prior to uterine evacuation and were assayed for human chorionic gonadotropin (hCG). RESULTS: Four of nine HME samples significantly (P < 0.05) suppressed CTLL2 proliferation, while five exhibited no suppressive activity. A strong positive correlation (r = 0.639) was noted for the relationship between gestational age of the molar pregnancies and interleukin-2(IL-2)-stimulated CTLL2 proliferation (expressed as % of control) in the presence of HME (500 μg/mL). This indicates that HME suppression of CTLL2 proliferation is highest in early gestation and then declines with increasing gestational age. A similar correlation was observed between estimated uterine size at surgery and CTLL2 proliferation with added HME, although the association was not as strong (r = 0.359). No association was noted between hCG levels and CTLL2 proliferative responses (r = ?0.091). CONCLUSIONS: The results of this study suggest that production of immunosuppressive factors by hydatidiform mole trophoblast is developmentally regulated, and decreases with advancing gestation.     

Is previous use of hormonal contraception associated with a detrimental effect on subsequent fecundity?

BACKGROUND: The effects of contraception on subsequent fecundity are yet to be substantiated. METHODS: A total of 2841 consecutive pregnant women in Hull and Sheffield completed questionnaires inquiring about time to pregnancy (TTP), contraceptive use, pregnancy planning, previous pregnancies, age and lifestyle characteristics of each partner. Outcome measures were mean TTP, conception probability and odds of subfecundity after discontinuing each contraceptive method. RESULTS: TTP following long-term combined oral contraceptive (COC), short-term intrauterine device (IUD) or any duration of injectable use were 2.0-, 1.6-, 3.0-fold longer than TTP after condom use, respectively. Within 6 months of discontinuing COC or injectable use, conception probabilities were 0.86 and 0.34, respectively, whereas those relevant to other methods were not significantly different. All levonorgestrel intrauterine system (IUS) users conceived within 1 month. Relative to condoms, odds of subfecundity after COC, injectable and short-term IUD use were 1.9, 5.5, 2.9, respectively. The effect of COC and injectables was stronger with long-term use, in older, obese or oligomenorrhoeic women. Similar results were obtained after adjustment for potential confounders. CONCLUSIONS: A significant reduction in fecundity occurs after COC, IUD or injectables, which is dependent on the duration of use. The effect of COC and injectables is evident in women with a potentially compromised ovarian function. Use of progesterone-only pills or IUS is not associated with a significant effect.     

Comparison of alterations in fetal regional arterial vascular resistance in appropriate-for-gestational-age singleton, twin and triplet pregnancies.

The objective of this longitudinal study was to evaluate alterations in fetal vascular resistance of fetal peripheral arteries with advancing gestation in singleton appropriate-for-gestational-age (S-AGA), twin appropriate-for-gestational-age (Tw-AGA) and triplet appropriate-for-gestational-age (Tri-AGA) infants. Colour Doppler flow imaging and pulsed Doppler ultrasonographic examinations were performed on 35 S-AGA, 52 Tw-AGA and 12 Tri-AGA fetuses. The pulsatility index for middle cerebral artery (MCAPI), umbilical artery (UAPI), descending aorta (DAPI), splenic artery (SAPI), renal artery (RAPI) and femoral artery (FAPI) was measured as vascular resistance every 2 weeks after 15 weeks of menstrual age until delivery. Optimal models and normal ranges for pulsatility index for each artery in each group were generated. The alterations in various fetal regional arterial pulsatility indices with advancing gestational age showed no significant differences in S-AGA, Tw-AGA and Tri-AGA infants, respectively. These results suggest that there is no significant difference for regional arterial vascular resistance in AGA fetuses among singleton, twin, and triplet pregnancies, whereas there was a slight difference in fetal growth pattern among singleton, twin, and triplet pregnancies described in our previous investigation.     

Pregnancy: Early (34-56 days from last menstrual period) ultrasonographic measurements in normal pregnancies

To assess early embryonic growth and development, 361 pregnancieswere studied from 34 to 56 days from last menstrual period.All pregnancies had a subsequent successful outcome. Transvaginalultrasonography was per formed using an Acuson 128 X P110 witha 5–7.5 MHz probe. Gestational sac diameter, embryonicpole length and embryonic heart rates were measured. Embryonicheart rates were determined by M-mode. Gestational sac diameter,embryonic pole length and embryonic heart rate Increased linearlyrelative to gestational age and to each other. Regression equationscomparing gestational sac diameter and embryonic pole lengthas well as comparing embryonic heart rate with gestatlonal sacdiameter and embryonic pole length were constructed. To he normal,gestations that have (i) sac diameter of 20 mm and 30 mm shouldcontain at least a 2 mm and 5 mm embryo with embryonic heartrates of at least 75 and 100 heats per mm, respectively; and(ii) embryos measurIng 2 mm, 5 mm, 10 mm and 15 mm should displayembryonic heart rates of at least 75,100,120 and 130 beats perminute respectively.     

Postmortem chorionic villus sampling: correlation of cytogenetic and ultrasound findings

We performed chorionic villus samplings (CVS) in 795 cases in the first trimester during a 13-month period. Of these 35 were found to have a blighted ovum or missed abortion prior to the procedure. Nineteen women consented to have CVS. Ultrasonographic and cytogenetic findings in these 19 pregnancies were correlated. Expected gestational age was determined by last menstrual period. Observed gestational age was determined by crown rump length (CRL) (12 pregnancies) or gestational sac (GS) (7 pregnancies without fetal pole). The differences in days between the estimated and observed gestational ages was determined for each pregnancy. In all 19 CVS samples cytogenetic diagnosis documented aneuploidy. Ten cases had chromosome abnormalities virtually always lethal in the embryonic period (group I). Nine pregnancies had defects with moderate potential for fetal viability (group II). Gestations with low viability potential (group I) had estimated minus observed gestational age discrepancies (23.4 +/- 8.3 days) significantly greater than gestations with moderate viability potential (group II) (8.9 +/- 4.3 days) (P less than .001). The absence of a fetal pole was more common in group I. CVS in pregnancies with missed abortion or blighted ovum is feasible and has a high likelihood of documenting aneuploidy. Furthermore, the more severe the anomaly the more likely there will be very early fetal demise or intrauterine growth retardation.     

Successful pregnancy by transmyometrial and transtubal embryo transfer after IVF in a patient with congenital cervical atresia who underwent uterovaginal canalization during Caesarean section: case report

Successful pregnancy in a patient with congenital cervical atresia is a great challenge for assisted reproductive techniques and reproductive medicine. We report a case of successful pregnancy by transmyometrial and transtubal embryo transfer simultaneously after in-vitro fertilization (IVF) in a 33 year-old patient with congenital cervical atresia diagnosed at the age of 18 years. The patient had experienced cyclic abdominal pain and amenorrhoea since she was 13 years old. She had had two unsuccessful attempts to create a new uterovaginal canal in another hospital. At the age of 32 years, she was referred to our unit and had a successful pregnancy after transmyometrial and transtubal embryo transfer. Caesarean section was performed at 36 weeks gestation due to progressive pre-eclampsia and gestational diabetes. A healthy male baby weighing 2812 g was safely delivered. Uterovaginal canalization with amniotic membrane for the covering of the neo-endocervical wall was performed during Caesarean section. Normal menstrual outflow and symptomatic relief have continued for 5 months after the operation. To the best of our knowledge, this is the first reported case of successful pregnancy by transmyometrial and transtubal embryo transfer as well as uterovaginal canalization performed during Caesarean section in a patient with congenital cervical atresia.     

The obstetrical and neonatal outcome of babies born after single-embryo transfer in IVF/ICSI compares favourably to spontaneously conceived babies

BACKGROUND: Recently, concern has risen about poor obstetrical and neonatal outcome of singletons after IVF/ICSI. Because the population of patients receiving single-embryo transfer (SET) resulting in singleton pregnancies is different from the one that would have become pregnant (with a singleton) before SET was introduced, we wanted to investigate whether the outcome of singleton pregnancies after SET differed from spontaneously conceived singletons. METHODS: The obstetrical and early neonatal outcome of all pregnancies originating from SET after IVF/ICSI procedures between 1 January 1998 and 31 December 2003, was prospectively collected and analyzed. RESULTS: Data from 251 singleton pregnancies and births after SET were analyzed and compared to data from 59,535 spontaneously conceived singletons retrieved from the Centre for Perinatal Epidemiology. The mean birthweight of the singletons after SET was 3322 g (+/-538 SD) versus 3330 g (+/-531 SD) for the spontaneously conceived singletons (P = 0.82). The mean gestational age was 38.7 weeks (+/-1.9 SD) for SET and 38.9 weeks (+/-1.8 SD) for spontaneously conceived singletons (P = 0.06). The proportion of very preterm birth (<32 weeks) was 0.8% in each group, and the proportion of preterm birth (<37 weeks) was 10.0% for SET singletons and 6.24% for spontaneous singletons (P = 0.03). However, mean birthweight of very preterm, preterm and term SET singleton babies was similar to the mean birthweight in every category of gestational age in the spontaneous conceived control group. Stillbirth was 0.4% for both populations (P = 0.99). CONCLUSIONS: Good prognosis patients, in whom SET is applied, do not only have a higher chance of conception but do not have an unfavourable outcome of their singleton baby when compared to spontaneous singletons.     

Risk factors for spontaneous abortion: a case-control study in France.

A case-control study was conducted in seven maternity hospitals in the Paris area in 1988 to evaluate the role of several risk factors in spontaneous abortion. A total of 279 cases and 279 controls were compared for socio-demographic characteristics, reproductive history and for conditions of conception. Prior fetal losses [odds ratio (OR) = 2.30 for n greater than or equal to 2; 95% confidence interval (CI) = 1.17-4.61] and maternal age at pregnancy (greater than 30 years) appeared to be major and independent risk factors of spontaneous abortion. Other factors associated with an increased risk of fetal loss were: geographical or ethnic origin (OR = 2.85 for North African women; 95% CI = 1.58-5.10); psychological problems at the time of conception, either related to the outcome of the pregnancy (OR = 3.08; 95% CI = 0.92-10.25) or unrelated to this outcome (OR = 3.35; 95% CI = 1.41-8.00). The following factors were not associated with spontaneous abortion: gravidity, parity, prior induced abortion, prior sexually transmitted diseases and Chlamydia trachomatis serology, menstrual cycle abnormalities, induced conception cycle and in-vitro fertilization, cigarette smoking, current or past use of combined oestrogen/progestagen pill or intrauterine device. These findings confirm the importance of two risk factors for fetal loss: maternal age and number of prior spontaneous abortions. Two risk factors, ethnic origin and psychological problems at the time of conception are also identified, which require further study.     

Normal pregnancy outcome after inadvertent exposure to long-acting gonadotrophin-releasing hormone agonist in early pregnancy.

Five infertile women exposed to long-acting gonadotrophin-releasing hormone agonist (GnRHa) during early pregnancy were studied to assess the risks of embryotoxicity on the outcome of their pregnancies. All the patients were diagnosed as stage 3-4 endometriosis following laparoscopy. Long-acting GnRHa (3.75 mg) was given in the first 3 days of their preceding menstrual period. Four of the five patients had two GnRHa injections and the last patient had three GnRHa injections. All patients were advised to use a barrier contraception (condoms) throughout the treatment period. Since all complained of no bleeding following the initial injections, human chorionic gonadotrophin (beta-HCG) concentrations were tested in order to rule out any pregnancy. Ultrasonographic examinations were commenced routinely and all patients had amniocentesis at 16-18 weeks gestational age. Genetic analysis revealed a normal karyotype in all fetuses. All five pregnancies progressed to term without complication, and normal healthy infants were delivered. Although there are still no clear answers concerning teratogenic and hormonal effects of GnRHa exposure in pregnancy, our data may suggest that luteal function, genetic structure and pregnancy outcome are not adversely affected by GnRHa. Since possible subtle effects on fetal endocrine organs cannot be disregarded, close monitoring is still needed in GnRHa-exposed pregnancies.     

Early luteal phase treatment with mifepristone (RU 486) for fertility regulation

Mifepristone (RU 486) is an antiprogestin which interacts withprogesterone at the receptor level. Administration of mifepristoneimmediately after ovulation does not upset the menstrual cycle.However, the maturation and function of the endometrium is inhibitedand uterine contractility is changed. To test if these effectsare sufficient to prevent implantation, 21 women agreed to useone single treatment with 200 mg mifepristone on day luteinizinghormone (LH) + 2 monthly as their only contraceptive method.The women were treated for 1– 12 months. The time of theLH peak was determined in the urine by the women themselvesusing a rapid LH test (Ovu-quick, Organon). The overall numberof cycles studied was 169. In 12 cycles the women were unableto detect the LH peak. In these cycles no treatment was givenand the women advised to use barrier methods during the timeto menstruation. The remaining 157 cycles with a detectableLH peak were all ovulatory based on plasma progesterone measurement.One pregnancy occurred. On the basis of the time of the LH peak,it was retrospectively calculated that in 124 cycles at leastone act of intercourse occurred during the period 3 days beforeto 1 day after ovulation. The probability of pregnancy in thisperiod of the menstrual cycle is thus 0.008. The women did notcomplain of any treatment-related side-effects apart from slightbleeding for 2–3 days starting a few days after the dayof treatment in 35% of the cycles. The results show that theeffect of mifepristone on the endometrium is sufficent to preventpregnancy and indicate that treatment with antiprogestin canalso be used for contraceptive purposes.