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Biomedical subjects

P C Steptoe

Publications and source records attributed to P C Steptoe.

At least 19 recordsLinked to original sources

Doppler ultrasound studies of the uterine artery in spontaneous ovarian cycles.

Doppler studies of the uterine artery using an off-set Doppler transducer with a mechanical sector imaging transducer indicate clear changes in uterine perfusion during the ovarian cycle. In this study, 16 volunteers had Doppler studies performed at least twice weekly during spontaneous ovarian cycles. Endocrine assays were performed on each occasion to measure plasma oestradiol, progesterone and luteinizing hormone levels. Conventional criteria to assess uterine impedance using systolic/end diastolic ratio and Resistance Index were modified to obtain meaningful results and a new flow velocity wave form classification is presented. The results indicate increasing uterine perfusion with rising levels of plasma oestradiol and progesterone and a direct correlation with falling oestrogen levels in the follicular phase. We conclude that off-set mechanical sector duplex systems can be used effectively to monitor uterine responses to the hormone environment.

Arteries

Decreased uterine perfusion--a cause of infertility.

There have been several causes of infertility attributed to gamete quality, congenital anatomical abnormalities and surgical complications. Published research into the reasons for failure of implantation of embryos has been confined to histochemical and histological studies of the endometrium. This paper presents preliminary data from an ongoing study to test the hypothesis that poor uterine perfusion is a cause of failure of implantation of embryos. It would follow that poor uterine perfusion is a cause of infertility. One-hundred-and-fifty-three patients who had been unsuccessful in conceiving despite three previous in-vitro fertilization attempts have been studied. Doppler ultrasound studies of the ascending branch of the uterine artery, during spontaneous ovarian cycles, revealed a poor mid-secretory uterine response in 48% of patients studied. Patients with poor mid-secretory uterine response were treated with orally administered hormone therapy to improve the mid-secretory uterine response prior to subsequent embryo replacement. The results of subsequent in-vitro fertilization therapy in patients with good uterine response and in women with improved uterine response after hormone therapy are presented. The numbers of patients in each group are insufficient for statistical analyses, but the trends observed support the hypothesis that poor uterine blood flow is a cause of infertility. Further evaluation is warranted.

Adult

The effect of endogenous progesterone on basal body temperature in stimulated ovarian cycles.

Whilst it is well recognized that progesterone is involved in the elevation of body temperature following ovulation, the mechanism for this process has not been determined. In this study 87 patients undergoing in-vitro fertilization recorded their basal body temperature during one treatment cycle. Exogenous gonadotrophin therapy administered to induce multiple folliculogenesis considerably elevated periovulatory oestrogen levels and early luteal phase progesterone. Body temperature rapidly rose to plateau 48 h after follicular aspiration in all patients. The amplitude of the temperature rise was independent of the progesterone concentration and the type of hormonal stimulation. There was no correlation between the degree of elevation of progesterone and the amplitude of the rise in body temperature over the first 4 days of the luteal phase. It is postulated that serum progesterone levels do not directly control body temperature, but that an oestrogen-progesterone synergism may be involved.

Body Temperature

Observations on 767 clinical pregnancies and 500 births after human in-vitro fertilization.

Details of 767 clinical pregnancies and 500 births from Bourn Hall are reported. All treated patients included some over 40 years old, many with ovarian or uterine defects, male infertility, etc. Patients were treated during their natural cycle or stimulated with clomiphene or clomiphene and human menopausal gonadotrophin. Follicular maturation was induced by an endogenous luteinizing hormone surge or human chorionic gonadotrophin. A maximum of three embryos were replaced, except in a few patients receiving four. Twenty-eight percent of pregnancies aborted, occurring more frequently in patients who were over 40, with a complicated obstetric history, and given clomiphene alone. Approximately 18% of fetuses 'vanished' in multi-pregnancies. Seventy-one sets of binovular twins and nine sets of triplets have been born, and seven twins and three triplets are ongoing. Seventeen and a half per cent of patients aged 39 and less with one or more replaced embryos delivered one or more children, rising to almost 25% with three replaced embryos. A mean of 1.3 children were born per delivery when three embryos were replaced. Most deliveries were by Caesarean section. There were two cases of placenta praevia, one stillbirth, four major and eight minor anomalies. All the triplets, and some twins and singletons had low birth weights and were born prematurely. The sex ratio was 247 males to 253 females.

Abortion, Spontaneous

Implantation, abortion, and birth after in vitro fertilization using the natural menstrual cycle or follicular stimulation with clomiphene citrate and human menopausal gonadotropin.

The incidence of pregnancy and abortion was analyzed in 1679 patients having embryos replaced after oocyte recovery and in vitro fertilization in order to alleviate their infertility. In these patients, 364 pregnancies were achieved and 108 abortions occurred. Patients were treated either on their natural cycle, having a spontaneous luteinizing hormone (LH) surge to induce ovulation, or after ovarian stimulation using clomiphene citrate alone or in combination with human menopausal gonadotropin (hMG). The data were assessed in relation to the numbers of embryos replaced, the follicular stimulation and ovulation induction regime used, the dose of gonadotropins and the dose of antiestrogens, and the age of the patient. The most successful treatment for the number of live births per laparoscopy was the use of clomiphene citrate in combination with human menopausal gonadotropin followed by human chorionic gonadotropin (hCG) to induce follicular maturation and ovulation. This treatment produced a significantly higher (P less than 0.001) number of patients with multiple embryos (86.5%). There was no significant effect on pregnancy or abortion with a low (less than 400-mg) or high (greater than or equal to 400-mg) dose of clomiphene. The total dose of gonadotropins used did not influence the incidence of pregnancy or abortion. The use of hCG with hMG induced a significant (P less than 0.01) positive effect on the incidence of pregnancy. The incidence of pregnancy showed a progressive decline with increasing age but there was a highly significant (P less than 0.01) increase in the incidence of abortion with increasing age. With increasing numbers of embryos replaced, up to three, the incidence of deliveries increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous

Failure of in vitro fertilization and embryo replacement following infection with Chlamydia trachomatis.

Antibodies to Chlamydia trachomatis were detected in 54 (47.4%) of 114 infertile women attending Bourn Hall Clinic. Antibodies were solely of the IgG class and mainly of a low titer, suggesting past infection. Antibodies were found in significantly more patients with tubal damage (54.4%) than in women whose infertility was due to other causes (16.6%). Seventy-two women completed in vitro fertilization, with 52 having three embryos replaced. We found that this treatment offered the optimum chance of a pregnancy being established, and 20 (38.5%) of these women became pregnant. Antibodies to C. trachomatis were present in only six (30.0%) of the women becoming pregnant, whereas antibodies were found in 21 (65.6%) of those who failed to become pregnant. Thus past infection with C. trachomatis halved the success rate of in vitro fertilization in these patients. The implications of these findings are relevant to all aspects of infertility from prevention to in vitro fertilization treatment.

Adult

Pregnancy following in vitro fertilization using cryopreserved semen from a man with testicular teratoma.

Semen for cryopreservation was collected in a man with a testicular teratoma after unilateral orchidectomy but before chemotherapy which rendered him azoospermic. After two years artificial insemination using this semen in his wife failed repeatedly. The semen quality on thawing was extremely poor in terms of sperm motility. A pre-freeze motility of 90 per cent was reduced to 2 per cent, and the movement was graded as sluggish. Using the techniques of semen and oocyte preparation and in vitro fertilization, a number of cleaving embryos was produced. A pregnancy was established after four of these embryos were replaced in the wife. The pregnancy aborted spontaneously, but a subsequent course of treatment resulted in an on-going twin pregnancy. The potential of in vitro fertilization for overcoming the poor quality of semen after storage by cryopreservation from men with testicular neoplasms is discussed.

Adult

In vitro fertilization using cryopreserved donor semen in cases where both partners are infertile.

The incidence of pregnancy after in vitro fertilization (IVF) was studied in a group of 38 couples (55 cycles) where both partners were infertile. Cryopreserved donor semen (IVF-D) was used in all cycles. Results were compared with those in a control group of couples where the husband's semen was considered normal and only the wife was infertile. No significant differences were found between the IVF-D and control groups in the incidence of fertilization (80% versus 72%), pregnancy per cycle (33% versus 29%), and abortion (18% versus 20%), despite the considerably lower percentage of motile spermatozoa in the IVF-D group. Forty percent of patients, each treated unsuccessfully with at least 12 artificial inseminations with donor semen, became pregnant after one or two IVF-D cycles. It is concluded that IVF with frozen donor semen is a beneficial treatment for couples where both partners are infertile.

Female

Treatment of idiopathic infertility, cervical mucus hostility, and male infertility: artificial insemination with husband's semen or in vitro fertilization?

Couples with male infertility (n = 86), idiopathic infertility (n = 68), and cervical mucus hostility (n = 48) of a long duration were treated either by in vitro fertilization (IVF) or artificial insemination with husband's semen (AIH). The incidence of pregnancy per cycle in couples in whom the male partner was infertile was significantly (P less than 0.01) higher after IVF, compared with AIH (21% versus 5%, respectively). The differences were most apparent in couples with asthenospermia (47% versus 0%, respectively); no significant difference was found when the infertility was caused by oligospermia only (11% versus 9%, respectively). More patients with idiopathic infertility became pregnant after one cycle with IVF, compared with AIH (20% versus 8%, respectively); but, because of intragroup disparity in size, this difference was not significant. A highly significant difference (P less than 0.01) was found after one attempt with IVF, compared with AIH, in patients with cervical mucus hostility (38% versus 3%, respectively).

Cervix Mucus

Factors influencing the success of in vitro fertilization for alleviating human infertility.

The program for in vitro fertilization at Bourn Hall began in October 1980. Various types of infertility have been treated during this time using the natural menstrual cycle or stimulation of follicular growth with antiestrogens and gonadotrophins. Follicular growth and maturation are assayed by urinary estrogens and LH, monitored regularly during the later follicular stage. Many patients had an endogenous LH surge; others needed an injection of HCG to induce ovulation. All oocytes were recovered by laparoscopy. Wide variations occurred in the time interval between the start of the LH surge and oocyte recovery and between oocyte recovery and insemination. Embryos taken between the one- and the eight-cell stage were replaced into their mother, no standard procedure being adopted for all patients. The results of all treatments including patient's responses during the follicular and luteal phases, oocyte recovery, fertilization, cleavage, replacement, implantation, abortion, and birth and the effect of factors such as replacing two or more embryos, maternal age, and previous obstetric history are described in detail. The incidence of implantation after embryo replacement improved from 16.5% initially to 30% currently. More than 118 babies have been born, and many pregnancies are continuing.

Abortion, Spontaneous

Current status of in-vitro fertilisation and implantation of human embryos.

Between October, 1980, and April, 1983, embryos fertilised in vitro were replaced in the uteri of 1200 women. The "clinical" pregnancy rate rose from 16.5% from October, 1980, until September, 1982, to almost 30% in 1983. The proportion of pregnancies ending in abortion varied from 25-35%. Factors favourably modifying implantation rate were maternal age of under 40 years, priming with clomiphene alone, and the replacing of more than one embryo in the uterus. The replacing of two or more embryos, increasing maternal age, a poor obstetric history, and high levels of follicular oestrogens raised the chances of abortion.

Abortion, Spontaneous

Clinical aspects of pregnancies established with cleaving embryos grown in vitro.

Details are given of four pregnancies established by fetilization in vitro and planting cleaving embryos into the mother. The pregnancies were monitored by hormone assays in early pregnancy and by ultrasound scans. Amniocentesis was used to assess the levels of alpha-fetoprotein and the karyotype of the fetuses at 15 weeks. Placental function tests and X-rays were used to monitor late pregnancy in one patient. Three of the pregnancies began uneventfully and the fetuses were normal in all respects. Two were delivered at or near term, the third being aborted spontaneously at 21 weeks while the parents were on holiday. The fourth pregnancy did not develop normally and a triploid fetus was aborted 12 weeks after the last menstrual period. The clinical difficulties inherent in selecting patients and preparing them for treatment are described. Some possible improvements in techniques are also described.

Abortion, Spontaneous

Steroid production from 17alpha-hydroxypregnenolone and dehydroepiandrosterone by human granulosa cells in vitro.

Granulosa cells were aspirated 3--4 h before the expected time of ovulation from 10 follicles of 4 patients treated with gonadotrophins: 4 of the follicles were immediately preovulatory. The granulosa cells were cultured for 10 h with 17alpha-hydroxypregnenolone or dehydroepiandrosterone and samples of medium removed at 3 and 10 h were assayed for 6 steroids. Granulosa cells were unable to synthesize androgens from endogenous substrate or undertake conversions via the delta5 pathway, but cells from all follicles were capable of aromatizing exogenous androgens to oestrogens although this capability was reduced in cells from follicles beginning to luteinize. Granulosa cells from preovulatory follicles synthesized more progesterone from endogenous substrate than cells from follicles which had not begun to luteinize. The results provide further support for the two-cell theory of oestrogen biosynthesis whereby granulosa cells aromatize androgens which are synthesized by the thecal cells in vivo.

17-alpha-Hydroxypregnenolone