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Biomedical subjects

M G Hull

Publications and source records attributed to M G Hull.

At least 109 records · Page 6Linked to original sources

Osteoporosis and amenorrhea in young women.

Bone density of the radius was measured using both standard photon absorptiometry and X-ray computed tomography (CT) scanning, and of the femur using CT, in 21 young women with amenorrhea and estrogen deficiency due to hyperprolactinemia, 8 due to ovarian failure or weight loss, 17 postmenopausal women with bone fractures presumed to be due to osteoporosis, and 36 young normal controls. Bone density in the postmenopausal women was reduced by 18-20% in the radius and 11% in the femur (p less than 0.001). In the hyperprolactinemic group bone density was significantly reduced only in the femur (by 4%, p less than 0.01). Bone density appeared to be reduced in the other young amenorrheic women both in the radius (by 2-5%) and the femur (3%) but the difference was not significant, although the group was small. This and other studies of bone density suggest the need for prophylactic treatment to prevent osteoporosis in young women with amenorrhea and estrogen deficiency, whatever the cause.

Absorptiometry, Photon↗

Borderline hyperprolactinemia in infertile women: evaluation of the prolactin response to thyrotropin releasing hormone and double-blind placebo-controlled treatment with bromocriptine.

Twenty-two women with on average more than 3 years unexplained infertility including normal menstrual cycles were studied because of borderline hyperprolactinemia (repeated serum prolactin concentrations 400-1000 mU/l). Randomized double-blind treatment with bromocriptine 5 mg daily (leading to adequate prolactin suppression) or matching placebo, each for 4 cycles, resulted in a cumulative rate after 4 months of 14.3 +/- 10.6% (SE) in both groups. Also, the results of treatment were not significantly related to the serum prolactin response to an intravenous injection of thyrotropin releasing hormone, whether the response was blunted (ratio of peak to basal prolactin within 60 minutes of injection no greater than 2), intermediate (greater than 2 to 4) or normal (greater than 4).

Adult↗

Norethisterone treatment to control timing of the IVF cycle.

The use of norethisterone to control the timing of the preceding menstrual cycle and in consequence the timing of the in-vitro fertilization (IVF) cycle has been evaluated in a therapeutic IVF programme in which oocyte recovery was limited to 2 days each week. A consecutive series of 181 cycles after norethisterone and 29 untreated controls were compared. Menstruation occurred 2-3 days after norethisterone as planned in 82% of patients overall and in 87% of patients whose menstrual cycle length varied by no more than 2 days about the median. Norethisterone treatment did not significantly affect the outcome of IVF treatment compared with the controls in respect to cycles abandoned (12 versus 0%, respectively), peak follicular diameter (mean 18.1 mm versus 18.3 mm 48 h before laparoscopy), oocyte recovery rate (4.6 versus 4.5 per patient), oocyte morphology (63% versus 52% mature), or fertilization rate (72 versus 65% of mature oocytes). Clinical pregnancies were too few for comparison (rates 27 versus 9% per laparoscopy) but the overall rate (23%) indicated effectiveness of the methods. Prior norethisterone treatment appears to be an effective and useful means of controlling the timing of the oocyte recovery in IVF treatment.

Female↗

Identification of relaxin immunoreactivity in human follicular fluid.

Relaxin immunoreactivity has been found in samples of human follicular fluid collected from artificially stimulated pre-ovulatory follicles. The crude extract caused a reduction in the height of the contractions in a rat uterine strip bioassay. The reactive material eluted from Sephadex G50 in two major peaks. The first contained approximately 60% of the immunoreactivity and had an elution position corresponding to that of porcine relaxin, indicating a mol. wt of approximately 6000 daltons. The second peak was of a lower mol. wt, but its exact size and significance are unknown. A possible role for relaxin in the process of follicular rupture is suggested.

Biological Assay↗

Results of donor insemination related to specific male infertility and unsuspected female infertility.

Apparently normal but infertile women were treated by artificial insemination using fresh donor semen. In 228 couples in which the male partner was azoospermic the average monthly conception rate was 13.3% and the 12-month cumulative rate was 82.2% (SE 2.7%). In 116 couples in which the partner was oligospermic the monthly rate was 8.7% and the 12-month rate 66.6% (SE 5.0%, P less than 0.01). Previous smaller studies have given rise to conflicting or inconclusive results, but the reduced conception rates in the partners of oligospermic men in this large study suggests that unexplained female factors, discussed in the paper, contribute to their infertility in up to a third of patients.

Adult↗

Population study of causes, treatment, and outcome of infertility.

Specialist infertility practice was studied in a group of 708 couples within a population of residents of a single health district in England. They represented an annual incidence of 1.2 couples for every 1000 of the population. At least one in six couples needed specialist help at some time in their lives because of an average of infertility of 21/2 years, 71% of whom were trying for their first baby. Those attending gynaecology clinics made up 10% of new and 22% of all attendances. Failure of ovulation (amenorrhoea or oligomenorrhoea) occurred in 21% of cases and was successfully treated (two year conception rates of 96% and 78%). Tubal damage (14%) had a poor outlook (19%) despite surgery. Endometriosis accounted for infertility in 6%, although seldom because of tubal damage, cervical mucus defects or dysfunction in 3%, and coital failure in up to 6%. Sperm defects or dysfunction were the commonest defined cause of infertility (24%) and led to a poor chance of pregnancy (0-27%) without donor insemination. Obstructive azoospermia or primary spermatogenic failure was uncommon (2%) and hormonal causes of male infertility rare. Infertility was unexplained in 28% and the chance of pregnancy (overall 72%) was mainly determined by duration of infertility. In vitro fertilisation could benefit 80% of cases of tubal damage and 25% of unexplained infertility--that is, 18% of all cases, representing up to 216 new cases each year per million of the total population.

Adolescent↗

Endometriosis and ovulatory disorder: reduced fertilisation in vitro compared with tubal and unexplained infertility.

In-vitro fertilisation (IVF) was carried out once for each of 104 couples who had a single cause of infertility. The group with tubal damage was used as the reference for normal fertilising capacity of both oocytes and sperms: the IVF rates were 68% (71/105) per mature oocyte and 88% (37/42) for couples from whom mature oocytes were recovered. Couples with poor sperm/mucus penetration had reduced IVF rates: 32% (12/38) per oocyte and 60% (9/15) per couple. Sperm function, which was judged normal by means of standard seminal analysis and mucus penetration, was confirmed by normal IVF in unexplained infertility: 63% (37/59) per oocyte and 90% (18/20) per couple. Despite favourable sperm function in their partners, women with endometriosis (without tubal damage) had reduced IVF rates: 33% (19/58) per oocyte and 60% (9/15) per couple. These findings indicate that ovulatory disorder is present in endometriosis and suggest that it causes the associated infertility.

Adult↗

Ultrasound Doppler flow studies of the ovarian and uterine arteries.

The feasibility of studying ovarian arterial blood flow has been demonstrated, using an ultrasonic method combining real-time imaging and pulsed Doppler (the 'duplex' method). Results using a percutaneous full-bladder technique were validated by comparison with use of an ultrasound probe applied directly to the arteries at laparotomy. The ovarian arteries demonstrated qualitatively and quantitatively distinct flow patterns compared with the internal and external iliac arteries. From recorded waveforms a pulsatility index (PI) reflecting vascular impedance was calculated. The PI was found to be lower, indicating increased blood flow, in the artery supplying the ovary carrying the dominant follicle or corpus luteum. Serial studies suggest that this change occurs at an early stage of the menstrual cycle, possibly before the dominant follicle can be recognized by its size or increased hormone production. Uterine arterial flow was also detectable, more accurately abdominally than vaginally, and the changes typical of late pregnancy were already found to be present, though to a lesser degree, in the first trimester.

Arteries↗

Effectiveness of vaginal administration of progesterone.

Vaginal administration of 200 or 400 mg of progesterone in a wax suppository every 12 h in normal women was effective in rapidly achieving and maintaining serum progesterone concentrations at physiological levels appropriate to the midluteal phase of the ovarian cycle and early pregnancy. Given in the follicular phase for 5 days in five subjects at each of two doses, progesterone reached concentrations in serum after 4 and 12 h of 21-105 nmol/l (mean 46.4 nmol/l SD 17.2, n = 50) with 200 mg dosage and 21-101 nmol/l (mean 53.8 nmol/l SD 16.6, n = 49) with 400 mg dosage. There was no significant reduction in levels between 4 and 12 h after administration, in contrast to previously reported findings, suggesting that the wax base led to slow release of the hormone. The uptake of progesterone in the midluteal phase was assessed in 10 subjects by comparing successive cycles treated with progesterone or placebo in a randomized double-blind manner. Using only the 400 mg dosage, the mean serum progesterone level was raised by 69%, the untreated level being normal (38.17 SD 10.01 compared with 64.49 SD 23.22 nmol/l, n = 10). This was despite an assumed concomitant fall in endogenous hormone production as suggested by a 28% reduction in oestradiol-17 beta levels. Thus vaginal administration of progesterone in wax appears to be effective and convenient, and preferable to the use of other progestogens in various circumstances in which a fetus may be exposed to the drug.

Adult↗

Oestrogen measurement to predict multiple pregnancy from gonadotrophin therapy in amenorrhoea.

Twenty-four hour urinary oestrogen results obtained in 20 amenorrhoeic patients undergoing human menopausal gonadotrophin (hMG) therapy have been analysed in detail in an attempt to improve their value in predicting multiple conception. Of 96 treatment cycles 88 were acceptably stimulated including 76 presumed ovulatory (midluteal serum progesterone concentration greater than or equal to 30 nmol/l). Conception occurred in 27 (26% of all, 33% of ovulatory cycles), of which 10 were multiple (37%). The chance of conception or multiple conception could not be related to luteal progesterone or preovulatory peak urinary oestrogen levels (at least within the clinically imposed limits of the oestrogen values). Discriminant analysis applied to all oestrogen results in individual cycles failed to predict conception, but in the conception cycles was 86% successful in predicting a single or multiple conception. Multiple conceptions were associated with an earlier but slower rise in oestrogen excretion during the last 5 days of hMG therapy, although the starting and final oestrogen levels were approximately the same. Unfortunately, the differences were small and as conception cycles were in the minority and could not be distinguished from non-conception cycles the oestrogen results could not be used reliably in practice to predict multiple pregnancy.

Amenorrhea↗

Infertility.

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Family Practice↗

Human in-vitro fertilisation, in-vivo sperm penetration of cervical mucus, and unexplained infertility.

Oocytes were recovered at routine diagnostic laparoscopy for infertility after stimulation with clomiphene and human chorionic gonadotropin. The results of in-vitro fertilisation (IVF) with the husband's semen were compared in 3 distinct groups of fully investigated infertile couples. Those with bilateral tubal occlusion (36) were combined with fertile controls undergoing sterilisation (6) to form a "tubal" group for normal reference. In this tubal group 48/88 (55%) oocytes were fertilised, at least one oocyte being fertilised in each of 33/42 couples (79%). In couples with a negative or poor postcoital test (PCT), despite mostly normal semen analysis, 8/50 (16%) oocytes were fertilised in 6/21 (29%) couples. In couples with unexplained infertility and a positive PCT, 22/61 (36%) oocytes were fertilised in 17/25 (68%) couples. The results show that spermatozoa unable to penetrate preovulatory cervical mucus are generally also unable to fertilise the human oocyte. They emphasise the biological and prognostic importance of the PCT, and the hidden frequency of defective sperm function as a cause of unexplained infertility. Human IVF is likely to be a more helpful diagnostic investigation than hamster egg penetration testing because it is specific for individual couples. If IVF is to offer therapeutic hope to couples with impaired sperm/mucus penetration the fertilisation rates and the numbers of mature oocytes stimulated for recovery will both have to be high.

Cervix Mucus↗

Chlamydial serology in fertile and infertile women.

Species-specific circulating antibodies to Chlamydia trachomatis were found in 75% of 48 infertile women with damaged fallopian tubes, 47.5% of 40 parous women seeking sterilisation, 46% of 63 women seeking termination of pregnancy, 31% of 75 infertile women with normal fallopian tubes, and 24% of 72 women using barrier contraception. High titres of antibody (greater than or equal to 1/1024) were found in 46%, 15%, 16%, 8%, and 7% of these groups, respectively, and were common in those women with a history of pelvic inflammatory disease or use of an intrauterine device. Thus, although the presence of antibody to C trachomatis was correlated with tubal damage, it was not diagnostic of tubal disease, since a substantial number of pregnant or potentially fertile women also had serological evidence of chlamydial infection. However, the results show that high titres of chlamydial antibodies in infertile women indicate the need for early laparoscopy to assess tubal status.

Adult↗