M. G. R. Hull

Impaired implantation after in vitro fertilisation treatment associated with hydrosalpinx

Objective To study whether the presence of hydrosalpinx affected success after in vitro fertilisation (IVF) in women with inflammatory tubal damage.

Relative influence of serum follicle stimulating hormone, age and other factors on ovarian response to gonadotrophin stimulation

Objective To determine the relative value of the womans age, basal follicle stimulating hormone (FSH), basal luteinising hormone (LH) and menstrual cycle pattern (all denned prior to treatment) in predicting the ovarian response to gonadotrophin stimulation for in vitro fertilisation.

Ovarian Dysfunction in Endometriosis-Associated and Unexplained Infertility

Purpose: The impact of endometriosis and unexplained infertility on follicular function and fertilization of oocytes in cycles totally unperturbed by exogenous gonadotrophins, when compared with controls with tubal damage, were examined.Methods: In natural cycles, without any exogenous gonadotropins, endocrine and ultrasonographic studies of follicular maturation in 18 women with minor endometriosis (41 cycles), 15 women with unexplained infertility (31 cycles), and 34 women with tubal damage (88 cycles) were performed.Results: The endometriosis group had a significantly longer follicular phase (median: 15,13, and 13 days). Both endometriosis and unexplained infertility had significantly reduced LH concentrations in follicular fluid compared with tubal damage (median: 12.1, 11.5, and 15.9 IU/L, respectively). Endometriosis was associated with a significantly reduced fertilization rate compared with unexplained infertility or tubal damage (46, 65, and 69%, respectively).Conclusions: These data show continuing evidence of ovulatory dysfunction leading to reduced fertilization rates in women with minor endometriosis.

Smoking and decreased fertilisation rates in vitro

To examine possible mechanisms for the association between cigarette smoking and reduced fertility, we have measured the concentration of the nicotine metabolite cotinine in ovarian follicular fluid collected at the time of oocyte recovery during treatment for in-vitro fertilisation. In a group of women in whom follicular fluid cotinine could not be detected (limit of accurate measurement 20 ng/ml) 116 oocytes were collected, of which 84 became fertilised (72%), whereas among women with cotinine concentration greater than 20 ng/ml 20/45 (44%) oocytes did so (p < 0.01). The median fertilisation rates for individuals (range 1-8 eggs each) in the high and low cotinine groups were 57% and 75%, respectively (p < 0.05). These findings suggest that infertile women should be advised to stop or reduce smoking generally, and especially before treatment by in-vitro fertilisation.

Onset of the preovulatory luteinizing hormone surge: diurnal timing and critical follicular prerequisites

OBJECTIVEnTo determine the diurnal variation in the onset of the preovulatory LH surge in women.nnnDESIGNnProspective open cohort study.nnnSETTINGnUniversity hospital research program.nnnPATIENT(S)nThirty-five women with infertility resulting from tubal damage that was associated with minor endometriosis or with infertility of prolonged unexplained etiology.nnnINTERVENTION(S)nWomen underwent transvaginal ultrasonography and serum E2 estimation daily during monitored cycles before unstimulated natural cycle IVF: exogenous gonadotropins were not administered.nnnMAIN OUTCOME MEASURE(S)nSerum E2 concentration, follicle diameter, and endometrial thickness.nnnRESULTSnOf 169 cycles. 155 progressed to an ovulatory LH surge, of which 146 occurred within 8 hours of assessment of the outcome measures. The relationship between follicle diameter and E2 was weak, but an abnormal value for one always was countered by a normal value for the other.nnnCONCLUSIONSnMost women begin the preovulatory LH surge between midnight and 8:00 A.M., but with no particular variation by day of the week. The relationship between follicle size and serum E2 is not sufficiently strong to predict the LH surge confidently on the basis of only one variable, but the LH surge is unlikely to occur before either the follicle diameter has reached 15 mm and/or the serum E2 level has reached 600 pmol/L.

Relationship between midcycle luteinizing hormone surge quality and oocyte fertilization

OBJECTIVEnTo determine whether alterations in preovulatory follicular fluid (FF) levels of LH, FSH, and steroids are associated with the probability of fertilization.nnnDESIGNnRetrospective analysis of prospective study results.nnnSETTINGnReproductive medicine clinic of a university teaching hospital.nnnPATIENT(S)nInfertile women, with unstimulated, apparently regular cycles in an IVF research program.nnnINTERVENTION(S)nMeasurement of preovulatory FF levels of LH, FSH, E2, and P and serum LH levels by fluoroimmunometry.nnnMAIN OUTCOME MEASUREnOocyte fertilization.nnnRESULT(S)nThere were 84 transferable embryos (rate of normal fertilization and cleavage, 67%), and 41 oocytes (33%) failed to fertilize. Analysis of the matched FF showed that the median concentration of FF LH was significantly higher for cleaving embryos than for unfertilized oocytes (14.6 vs. 10.4 IU/L). Serum LH concentrations were similarly higher in cycles with cleaving embryos. There were no statistically significant differences in FF concentrations of FSH, E2, or P in the two groups.nnnCONCLUSIONnReduced preovulatory FF LH levels are associated with impaired fertilization of oocytes in vitro, despite normal FF FSH and steroid levels.

Intrauterine insemination: is it an effective treatment for male factor infertility?

Results were collected from 11 studies comparing intrauterine insemination (IUI) with intracervical insemination (ICI) of frozen donor semen, 10 studies comparing IUI with timed natural intercourse (NI) or ICI in couples with semen defects and seven studies comparing ICI with NI or ICI in couples with unexplained infertility. IUI significantly increased the pregnancy rate relative to favourably timed ICI in donor insemination (DI) with frozen semen both with and without gonadotrophin stimulation of the female partner (odds ratios (95% confidence interval) 1.92 (1.02–3.61) and 2.63 (1.52–4.54) respectively). The benefit of IUI tended to be less when the pregnancy rate for ICI was high and IUI had no benefit with fresh donor semen. Overall IUI was of significant benefit in the male factor couples compared with NI-ICI (odds ratio 2.20 (1.43–3.39) and the advantage appeared to be maintained when comparison was confined to properly timed ICI although the odds ratios were not significantly greater than 1. IUI had no benefit relative to favourably timed NI-ICI for couples with unexplained infertility; an apparent advantage overall was produced by studies where NI was late. None of the studies on male factor used a sperm function test to define male subfertility and three only included couples with good mucus penetration by sperm. The range of semen defects defined was such that many couples would have had a good chance of conceiving naturally given a normal female partner but nevertheless the overall pregnancy rate (4.8%) was considerably less than in the unexplained group (11.6%), suggesting that some sperm dysfunction was present. We conclude that the available evidence suggests that IUI is valuable for DI with cryopreserved semen and for couples with mild to moderately impaired semen quality and postulate that it overcomes failure to fertilize due to impaired mucus penetration and poor survival in the female reproductive tract.

Complications of pregnancy after infertility treatment: awareness and prevention

In subfertility practice there is a tendency not to think beyond the starting of a pregnancy as the index of success, yet the real objective is the birth of a baby, indeed a healthy baby. It is an especially cruel blow to a subfertile woman who miscarries or loses her baby at a late stage of pregnancy. By far the biggest risk of pregnancy loss is miscarriage, which is often related to the cause of infertility. Also of major concern is fetal or neonatal damage due to growth retardation and prematurity associated with multiple pregnancy. It is of practical importance to appreciate that many of these risks can be prevented or minimised. Apart from ovum donation, nothing can be done about a woman’s age, but the major impact of unavoidable miscarriage is not until the woman is over 38 to 40 years. Infertility practice should be organised efficiently to avoid delays that sometimes lead to definitive treatment too late. Also, in general gynaecological and surgical practice there should be awareness of the need to avoid unnecessary ovarian destruction which can lead to premature ageing effects.

Experience Using Preparations of Follicle-Stimulating Hormone Alone to Stimulate the Ovaries for Assisted Conception after Pituitary Desensitisation and Simplified Management of Treatment

The results are reported of 2,204 cycles of treatment started for in vitro fertilisation and embryo transfer or gamete intrafallopian transfer, during 5 years, 1990-1994, using only follicle-stimulating hormone (FSH) preparations to stimulate the ovaries following pituitary desensitisation, combined with greatly simplified scheduling and monitoring of treatment. The physiological principles underlying these choices are discussed. In all women under 40 years of age and men with normal sperm, the use of unpurified urinary FSH in 1990-1993 resulted in oocyte collection in 94% of cycles started, pregnancy in 29% and live births in 23%. Using highly purified urinary FSH (uFSH-HP; Metrodin HP) during 1994, the rate for oocyte collection was 97% and pregnancy 25% (birth rates not yet available). The difference compared with previous years was not significant. A study of 93 first cycles using uFSH-HP showed that the dosage required was usually (expressed as medians) 24 ampoules over 12 days (2 ampoules/day) resulting in 9 oocytes (range 2-36) of which 93% were mature and 64% resulted in cleaving embryos. The results are comparable with the best using human menopausal gonadotropin or unpurified FSH and classical detailed monitoring.

Osteoporotic fractures in young amenorrheic women

Two cases of osteoporotic fractures in young women are presented, which highlight the risks and need for prophylactic therapy.