Maternal age and emergency operative deliveries at term: a population-based registry study among low-risk primiparous women.

OBJECTIVE: To study the association between maternal age and emergency operative delivery. The roles of in-labour indications, and birthweight ≥ 4000 g, gestational age ≥ 42 weeks, induction of labour, and epidural use, according to maternal age were explored. DESIGN: Population-based study. SETTING: Medical Birth Registry of Norway and Statistics Norway. POPULATION: We studied 169 583 low-risk primiparous mothers with singleton, cephalic labours, at ≥37 weeks of gestation, from 1999 to 2009. METHODS: The associations between maternal age and mode of delivery were analysed using multinomial regression analyses, adjusting for sociodemographic factors. MAIN OUTCOME MEASURES: Emergency caesarean section and operative vaginal delivery. RESULTS: Of women aged ≥40 years, 22% had emergency caesarean sections and 24% had operative vaginal deliveries, giving adjusted relative risk ratios (RRRs) of 6.60 (95% confidence interval, 95% CI 5.53-7.87) and 3.30 (95% CI 2.79-3.90), respectively, when compared with women aged 20-24 years. Adjustments for sociodemographic factors only slightly changed the estimates. Dystocia was the main indication, followed by fetal distress. All of the listed factors increased the level of emergency operative deliveries, mainly because of an increase in dystocia. The increase in risk for emergency caesarean section by all factors, and for operative vaginal deliveries by epidural, were greater in older than in younger women, but were significant for epidural only. CONCLUSIONS: We found a close association between maternal age and emergency operative delivery in low-risk primiparas. Contributory factors increased the risk for both emergency operative delivery and epidural more in older than in younger women.

Hormone-responsive adenylyl cyclase in the human fallopian tube.

Hormone-responsive adenylyl cyclase (AC) activity in biopsies from normal human Fallopian tubes was studied. Enzyme activity with a Km of 0.15 mmol/L and a maximum velocity of 13.8 pmol/mg.min in the basal condition was demonstrated. The addition of prostaglandin E1 (PGE1), PGE2, PGF2a, vasoactive intestinal polypeptide, isoproterenol, and terbutaline increased enzyme activity, with no change in the Km. Maximum stimulation of AC activity was obtained with PGE1, resulting in a 2- to 8-fold increase in AC activity. The response of AC to PGE1 revealed a possible topographical variation, with lowest responses to PGE1 in the isthmus. No such segmental variation in AC activity and response was seen after stimulation with PGF2a, vasoactive intestinal polypeptide, or isoproterenol.

Obstetric outcome in singleton pregnancies after assisted reproduction.

OBJECTIVE: To compare the obstetric outcome of singleton pregnancies after various procedures of assisted reproduction with a control group. METHODS: Maternal and perinatal outcome in 355 assisted-reproduction singleton pregnancies (study group) with a duration of 140 days or more were compared retrospectively with a control group matched for age and parity. All assisted-reproduction pregnancies resulted from treatment in one university hospital, and all control subjects delivered in the obstetric department of the same hospital. The controls consisted of 643 women, also with singleton pregnancies, who were matched for age and parity. RESULTS: In the study group, the frequencies of pregnancy-induced hypertension and placenta previa were increased. More patients in the study group were delivered by elective cesarean. Pregnancies after assisted reproduction were of shorter duration, with an increased incidence of preterm birth. Infants in the study group had a lower mean birth weight than did those in the control group and were more frequently referred to a neonatal care unit. CONCLUSION: Singleton pregnancies resulting from assisted reproduction represent obstetric risk cases, and the patients should be offered special attention during the pregnancy, which will probably be their only one.

Increased systemic activation of neutrophils but not complement in preeclampsia.

OBJECTIVE: To investigate whether neutrophils and systemic complement are activated in pregnancies complicated by preeclampsia more than in normal pregnancies. METHODS: We measured native complement components and activation products in plasma by enzyme immunoassays in 19 women with uncomplicated pregnancies, 15 with preeclampsia before cesarean deliveries, and 16 nonpregnant women. Neutrophil activation was measured by specific enzyme immunoassays for myeloperoxidase and lactoferrin. RESULTS: Myeloperoxidase was significantly higher in women with preeclampsia (197 microg/L, 95% confidence interval [CI] 94, 646) than in women with uncomplicated pregnancies (124 microg/L, 95% CI 70, 289; P =.009), whereas lactoferrin did not differ between groups. C4 was decreased in preeclamptic women (0.16 g/L, 95% CI 0.07, 0.48) compared with women with uncomplicated pregnancies (0.21, 95% CI 0.10, 0.30, P <.001). There were no differences for the other native complement components. There was a significant decrease in C1rs-C1 inhibitor, 13 AU/mL (95% CI 9, 34) versus 19 (95% CI 13, 38) (P < or =.001) in normal pregnant women compared with nonpregnant women. There also was an increase in C3, C4, C9 (data not shown), C4bp, 132% (95% CI 94%, 161%) versus 91% (95% CI 57%, 128%); C3bc (7.4 AU/mL, 95% CI 4.2, 10.7) versus 4.8 AU/mL (95% CI 3.2, 7.3) and C4bc (8.6 AU/mL, 95% CI 5.7, 14.0) versus 3.5 AU/mL (95% CI 2.2, 6.7) in normal pregnant women compared with nonpregnant women (P < or =.001). CONCLUSION: Neutrophil activation in preeclampsia was shown by systemic increases in myeloperoxidase. Except for a decrease in C4, systemic complement activation could not be detected in preeclampsia.

Deoxyribonucleic acid flow cytometry of germ cells in the investigatin of male infertility.

DNA flow cytometry was applied to fine-needle aspiration biopsy specimens from the testes of 20 oligospermic or azoospermic men under investigation for infertility. All aspirations gave sufficient material for DNA flow cytometry, and no complications occurred after aspiration. In both groups many DNA patterns deviated from those observed in control specimens. In general, abnormally small testes were associated with the greatest deviations in DNA patterns. In specimens from certain azoospermic men the DNA distributions did not deviate from those of control samples, suggesting a block in the testicular excurrent ducts. These findings also suggest that DNA flow cytometry of aspirated testicular material can be used in the classification of tubular degeneration in males. The results are obtained within a short time, are quantitative and without bias, and the aspiration causes only little discomfort to the patient. The method can therefore be recommended as a very practical means of obtaining quantitative estimates of spermatogenesis in men being evaluated for infertility.

Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations.

OBJECTIVE: To investigate the impact of body weight (BW) and insulin levels on gonadotropin and androgen levels in women with the polycystic ovarian syndrome (PCOS). DESIGN: Comparative study of endocrinologic parameters in PCOS women. SETTING: University Hospital Reproductive Endocrinology Unit. PATIENTS: Thirty obese and 19 nonobese women with PCOS. Seven obese and 7 nonobese normal women. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone. Serum LH response to gonadotropin-releasing hormone (GnRH) administration and assessment of insulin resistance by the continuous infusion of glucose with model assessment (CIGMA) test. RESULTS: Fasting insulin levels correlated with body mass index (BMI). Basal LH levels correlated inversely with BMI. Nonobese women with PCOS had a higher LH response to GnRH than obese women with PCOS. Only obese women with PCOS showed insulin resistance and fasting hyperinsulinemia. CONCLUSIONS: The data suggest that women with PCOS may be divided into two subgroups: those with obesity, insulin resistance, hyperinsulinemia, and normal/minimally elevated LH levels and those with normal BW, elevated LH levels, and normoinsulinemia.

Prediction of response to controlled ovarian hyperstimulation: a comparison of basal and clomiphene citrate-stimulated follicle-stimulating hormone levels.

OBJECTIVE: To test the ovarian reserve in a high-risk population before controlled ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN: A prospective study comparing the outcome of a clomiphene citrate (CC) challenge test to the outcome of subsequent IVF cycles. SETTING: Unit for assisted reproductive technology in a university hospital. PATIENTS, PARTICIPANTS: Ninety-one infertile women with an age of 35 years or more, who had previous ovarian surgery or who had been diagnosed with ovarian endometriosis. MAIN OUTCOME MEASURE: Relate follicle-stimulating hormone (FSH) levels before and after CC to frequency of cancellation of an IVF cycle because of a poor follicular response. RESULTS: Twenty-one patients had elevated basal levels of FSH. Thirty-seven patients, including 20 with high basal levels, showed an excessive FSH response to CC with an FSH level after CC above the 95% confidence limit. Clomiphene citrate-stimulated FSH levels correlated better than basal levels with response to controlled ovarian hyperstimulation. An excessive FSH response to CC predicted a poor response outcome of subsequent controlled ovarian hyperstimulation for IVF with 85% accuracy. CONCLUSION: Follicle-stimulating hormone response to CC predicts subsequent follicular response to controlled ovarian hyperstimulation.

Pregnancy after transfer of cryopreserved embryos in clomiphene citrate resistant polycystic ovarian syndrome.

Transfer of cryopreserved embryos in PCOS patients resistant to CC stimulation is an intriguing problem. Ovarian stimulation with hMG/hCG to create a secretory endometrium, will entail an unnecessary risk of OHSS. In this case study, we report the accomplishment of a successful pregnancy after transfer of cryopreserved embryos after secretory transformation of the endometrium by E2/P substitution in the absence of corpus luteum formation. However, the success rate of this treatment modality in terms of pregnancy per embryo transfer has still to be evaluated in an ongoing study.

Stimulation with human menopausal gonadotropin versus follicle-stimulating hormone after pituitary suppression in polycystic ovarian syndrome.

Stimulation with human menopausal gonadotropin (hMG) or follicle-stimulating hormone (FSH) was compared in 34 patients with polycystic ovarian syndrome after pituitary gonadotrope suppression with buserelin acetate. No differences were seen in the hormone parameters observed. Also, the duration of the stimulation period and the dose of gonadotropin used were the same. In both groups a multifollicular response was seen. Oocyte retrieval and in vitro fertilization resulted in identical ratios of mature to total oocytes and cleavage rates. Nine pregnancies occurred, four in the hMG group and five in the FSH group. Of the nine pregnancies, two were the result of transfer of frozen-thawed embryos in estradiol and progesterone substituted cycles.

The first attempt at IVF treatment. Results and requirements for a satisfactory success rate.

The purpose of this study was to report the success rate of the first IVF treatment in 161 patients who attended our department in 1988. The indications for IVF were tubal damage in 84 couples (52.1%), unexplained infertility and endometriosis (with patent tubes) in 61 couples (37.9%), and polycystic ovarian syndrome in 16 couples (10%). Clinical pregnancies were diagnosed in 40 patients, giving an overall clinical pregnancy rate of 35.4% per embryo transfer. In the group of patients with unexplained infertility or endometriosis one in three of the embryo transfer cycles will predictably result in a birth, one in four in the group of patients with tubal damage or polycystic ovarian syndrome. These results invite discussion of the possible reasons for the success of our IVF program.

IVF/ICSI outcome and serum LH concentration on day 1 of ovarian stimulation with recombinant FSH under pituitary suppression.

BACKGROUND: Down-regulation with GnRH agonist has been suggested to result in a profound suppression of LH bioactivity, reduced estradiol synthesis, and thus impaired IVF and pregnancy outcome. The aims of this study were: (i) to assess the usefulness of serum LH measurement on stimulation day 1 as a predictor of ovarian response, conception and pregnancy outcome in patients treated with long-term down-regulation with GnRH agonist and recombinant FSH, and (ii) to define the best threshold LH value, if any, to discriminate between women with different outcomes of IVF. METHODS: Records of 2625 cycles in 1652 infertile women undergoing IVF (n = 1856) and/or ICSI (n = 769) treatment were reviewed. RESULTS: The range of LH concentrations on stimulation day 1 overlapped among non-conception cycles, conception cycles, ongoing pregnancies and early pregnancy losses. Receiver operating characteristic (ROC) analysis showed that serum LH concentrations on stimulation day 1 were unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.51; 95% CI: 0.49-0.54) or ongoing pregnancies versus early pregnancy loss groups (AUC(ROC) = 0.52; 95% CI: 0.47-0.57). Stratification for various low serum levels of LH did not reveal significant differences with respect to conception or pregnancy outcome among different LH levels on stimulation day 1. CONCLUSIONS: Serum LH concentration on stimulation day 1 cannot predict ovarian response, conception and pregnancy outcome in women receiving long-term down-regulation during assisted reproduction treatment.

Azoospermia and oligozoospermia etiology and clinical findings.

Three hundred sixty infertile men with sperm counts below 10 million/ml have been through a complete clinical investigation. The most important etiological factors are discussed and the findings at the clinical examination of the genitalia externa and prostate/seminal vesicles are reported. Unilateral or bilateral small and/or soft testes were present in about 60% of the cases. The highest incidence of abnormalities at the examination of the genitals is in conformity with the poor semen qualities. About 50% of the patients had abnormal elevated follicle stimulating hormone (FSH) serum levels, indicating severe functional disorders in the germinal epithelium. Proper treatment is hardly available among these men, but it is important that, where possible, prophylactic measures are taken to avoid the condition developing.

An andrological study of 51 fertile men.

Andrological examination were performed on 51 healthy volunteers whose wives were pregnant. The men underwent the same clinical examinations as men in infertile couples. The results of these examinations indicate: a) a broad range of semen qualities exist in the normal fertile population several of which by previously defined standards could by considered pathological, b) that current ideas of those factors which are believed to be responsible for diminished semen quality in infertile men should by critically reexamined, nd c) greater investigations of normal fertile groups to delineate more clearly the differences between fertile and infertile men.

Assisted reproductive technology.

Several aspects of reproductive technology are discussed. In tubal infertility, the choice between surgery or in vitro fertilization and embryo transfer (IVF-ET) is addressed. In cases with bilateral distal occlusion or otherwise bad prognosis, IVF is probably more successful and less expensive. IVF in unstimulated cycles has given promising results, with pregnancy rates comparable to the results from the National IVF-ET Registry. If these results can be confirmed by more studies they will probably have a great impact on the choice of treatment in tubal infertility. The results obtained with various transfer procedures in nontubal infertility have still to prove tubal transfer to be a more effective procedure than IVF. Finally, studies on microinsemination in male infertility or unexplained infertility with previous fertilization failure in IVF show promising results with the subzonal insemination and partial zona dissection procedures.

GIFT, ZIFT, and related techniques.

This review focuses on the theoretical backgrounds for tubal gamete and zygote/embryo transfer, as well as the clinical results of gamete intrafallopian transfer (GIFT), which are compared with other non-fertilization procedures in infertile women with patent fallopian tubes. While GIFT and zygote intrafallopian transfer (ZIFT) probably result in a more synchronized entry of embryos into the uterine cavity, prospective, randomized studies have not shown these methods to be preferable to conventional in-vitro fertilization and embryo transfer. Nevertheless, co-culture with various cell types seems to yield more viable embryos with a high rate of implantation. The promising results with co-culture do not seem to be a cell- or species-specific phenomenon. This non-specific positive or negative conditioning effect of co-culture on embryo quality indicates that more optimal culture media for in-vitro fertilization can probably be devised. The requirements of laparoscopy and general anesthesia with GIFT have prompted the development of simpler methods based on fertilization in vivo. Various methods of artificial insemination combined with controlled ovarian hyperstimulation yield comparable results with GIFT in unexplained infertility. In endometriosis, GIFT seems to give better results compared with insemination techniques. Less invasive transcervical gamete and embryo transfer techniques have now been established, obviating the need for operating theater facilities.

Pregnancy after gamete intrafallopian transfer.

A couple with a history of 6 years' unexplained infertility was treated by gamete intrafallopian transfer (GIFT). Thus, oocytes were obtained by laparoscopy and immediately placed in a transfer catheter together with sperms. The oocyte/sperm preparation was injected into the Fallopian tube via a separate trochar under laparoscopic direction. Four weeks later pregnancy was confirmed by ultrasound.

Obstetric and perinatal outcome in pregnancies after assisted reproduction.

Infertile couples who seek medical advice have one single hope: to have one or more children. Therefore, pregnancy rates per cycle of any assisted reproductive technique that include early miscarriages and ectopic pregnancies are of little interest to them. They want to know their chances of having a baby. When counselling the patients, information on obstetric and perinatal outcome is necessary.

Precancerous lesions of the cervix uteri in infertile women.

A study of 318 patients with tubal infertility and a control group of 200 unselected infertile women yielded 14 (4.4%) and 1 (0.5%), respectively, with precancerous lesions of the cervix uteri. The one patient in the control group with severe dysplasia was later shown to have tubal infertility. The overall incidence of premalignant lesions of the cervix uteri as reported to the National Cancer Registry of Norway was 0.1% for the age group and period studied. Women with tubal infertility represent a small but comparatively high risk group for the development of precancerous lesions of the cervix uteri.

Serum prolactin and radiological skull examinations in infertile men with azoospermia or severe oligozoospermia.

Measurements of serum prolactin, FSH, LH, testosterone, and oestradiol and radiological examinations of the skull were carried out in 142 infertile men with sperm counts below 10 millions/ml. The prolactin levels were compared to those observed in 27 fertile men. Six of the infertile men showed high levels of prolactin. Two of these men had earlier been hypophysectomized, and the sella turcica was found to be abnormal on the roentgenograms. In the remaining four men the sella turcica was normal, and serum gonadotrophins, testosterone and oestradiol were within normal range, except for one man who displayed a very high FSH. The testis biopsies from these four men showed severe hypoplasia, signalling that treatment of the infertility with bromocriptine may be of limited value.

Sperm penetration in capillary tubes with albumin-Ringer solutions.

Linear penetration of sperm from 65 different semen samples was investigated in Ringer solutions containing 1%, 3%, and 6% bovine albumin and in cervical mucus by use of the capillary tube test. A high degree of correlation was observed between the penetration distances recorded in the Ringer-albumin solutions, particularly in the 3% and the 6% solutions, as compared with those observed in cervical mucus. The relative number of spermatozoa with abnormal configuration was found to be markedly lower in the upper segment of the tubes, indicating a relationship between propulsive motility and normal morphology.