B. A. Lieberman

Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin's lymphoma.

BACKGROUND Infertility is a common late effect of chemotherapy and radiotherapy, and has a substantial effect on the quality of life for young survivors of cancer. For men, semen cryopreservation is a simple way of preserving reproductive potential but for women, storage of mature eggs rarely proves successful, and the alternative-immediate in vitro fertilisation with cryopreservation of embryos-is not always appropriate. Reimplantation of cryopreserved ovarian tissue has been shown to restore natural fertility in animals. We applied this technique in a woman who had received sterilising chemotherapy for lymphoma. METHODS A 36-year-old woman underwent a right oophorectomy with cryopreservation of ovarian cortical strips before receiving high-dose CBV chemotherapy for a third recurrence of Hodgkins lymphoma. 19 months later, when serum sex steroid analysis confimed a postmenopausal state, two ovarian cortical strips were thawed and reimplanted-one onto the left ovary and another at the site of the right ovary. FINDINGS 7 months after reimplantation of ovarian cortical strips, the patient reported resolution of hot flashes and, for the first time, oestradiol was detected in the serum. This finding was associated with a decrease in the concentrations of follicle-stimulating hormone and luteinising hormone, and ultrasonography revealed a 10 mm thick endometrium, a poorly visualised left ovary, and a 2 cm diameter follicular structure to the right of the midline. The patient had one menstrual period, but by 9 months after the implantation, her sex steroid concentrations had returned to those seen with ovarian failure. INTERPRETATION Orthotopic reimplantation of frozen/thawed ovarian cortical strips is a well tolerated technique for restoring ovarian function in women treated with sterilising chemotherapy for cancer.

The use of biosynthetic human growth hormone to augment ovulation induction with buserelin acetate/human menopausal gonadotropin in women with a poor ovarian response*†

The present study has demonstrated the usefulness of GH in augmenting buserelin acetate/hMG to stimulate the rate of growth of follicles in women regarded as poor responders. The PR achieved was extremely encouraging in a group of patients whose prognosis was otherwise poor. Further studies are required to confirm these preliminary data.

Pelvic pain in women.

The clinical and psychological characteristics of 18 women with pelvic pain but no demonstrable pathology have been compared with those of 17 women with a similar complaint but some form of pelvic pathology and a control group of 9 women with no gynecologic problems. The results suggest that pelvic pain can have a psychosomatic origin which is amenable to short-term psychotherapeutic measures.

Children born after intracytoplasmic sperm injection: population control study

Intracytoplasmic sperm injection is often successful for treatment of male infertility; over 20 000 children have been born as a result.1 This bypassing of natural barriers to sperm selection has raised concerns about the children conceived.2 We report a population control study of children born in the United Kingdom as a result of this treatment. Children between 12 and 24 months old who had been singleton births were identified from a list of couples who had received the treatment and their parents were invited to participate; 123 of 137 families (90%) agreed. Control children, conceived naturally, were recruited from associated nurseries (105/123) or were social peers of cases (18/123). Altogether, 123 children born after intracytoplasmic sperm injection (study children) and 123 control children were seen. Children were matched for social class, maternal educational level, region, sex, and race but not maternal age. Multiple births were excluded to avoid confounding factors. Primary outcome measures were developmental scoring on the Griffiths scales of mental development3 and rates of congenital abnormalities. The Griffiths scales are an objective method of assessing development which uses five subscales. All subscales …

THE POSSIBLE ADVERSE EFFECT OF PROPRANOLOL ON THE FETUS IN PREGNANCIES COMPLICATED BY SEVERE HYPERTENSION

A retrospective study is presented of the effect of propranolol on fetal outcome in pregnancies complicated by maternal hypertension. In nine pregnancies in which propranolol was given to markedly hypertensive women (diastolic blood pressure over 105 mm Hg) the fetal outcome was worse than in 15 patients using other hypotensive agents. The probability of fetal or neonatal death was related to the amount of proteinuria and the presence of parenchymal renal disease but was also significantly higher when the mother had been treated with propranolol. Experimental evidence suggests that beta‐adrenergic blockade is harmful to the hypoxic fetus, for these reasons the use of propranolol in hypertensive pregnancies complicated by placental insufficiency may be contraindicated unless there is no satisfactory alternative.

Outcome in children from cryopreserved embryos.

A cohort of 91 children from cryopreserved embryos and 83 control children who were conceived normally had their development assessed using the Griffithss scales of mental development. The controls (81 singletons and two twins) of a similar age, sex, and social class were selected from siblings, cousins, and peers of the cryopreserved embryo group (68 singleton, 20 twins, and three triplets). Children from cryopreserved embryos had a lower mean birth weight and mean gestational age and a higher proportion were born by caesarean section. One child from the cryopreserved embryo group had Downs syndrome, three had squints, and four had conductive hearing loss while in the control children, six had squints, and nine had conductive hearing loss. In both groups, including the child with Downs syndrome, the mean Griffithss quotient was greater than the standard 100. In the children from cryopreserved embryos, the singleton and multiple birth subgroups had statistically similar assessment results. The mean (SD) Griffithss quotient was 105.69 (13.55) in children from cryopreserved embryos and 108.18 (9.80) in controls at a chronological age of 25.08 (12.86) and 29.19 (14.65) months respectively. Overall, the development in children from cryopreserved embryos did not cause concern though formal testing had highlighted small differences compared with other children conceived normally and of a similar social class.

Expression of genes involved in early cell fate decisions in human embryos and their regulation by growth factors

Little is understood about the regulation of gene expression in human preimplantation embryos. We set out to examine the expression in human preimplantation embryos of a number of genes known to be critical for early development of the murine embryo. The expression profile of these genes was analysed throughout preimplantation development and in response to growth factor (GF) stimulation. Developmental expression of a number of genes was similar to that seen in murine embryos (OCT3B/4, CDX2, NANOG). However, GATA6 is expressed throughout preimplantation development in the human. Embryos were cultured in IGF-I, leukaemia inhibitory factor (LIF) or heparin-binding EGF-like growth factor (HBEGF), all of which are known to stimulate the development of human embryos. Our data show that culture in HBEGF and LIF appears to facilitate human embryo expression of a number of genes: ERBB4 (LIF) and LIFR and DSC2 (HBEGF) while in the presence of HBEGF no blastocysts expressed EOMES and when cultured with LIF only two out of nine blastocysts expressed TBN. These data improve our knowledge of the similarities between human and murine embryos and the influence of GFs on human embryo gene expression. Results from this study will improve the understanding of cell fate decisions in early human embryos, which has important implications for both IVF treatment and the derivation of human embryonic stem cells.

THE INFLUENCE OF MATERNAL ANALGESIA ON NEONATAL BEHAVIOUR: I. PETHIDINE

Neonatal behaviour in a group of infants whose mothers received pethidine during labour was assessed at delivery and during the first six weeks of life by means of the Brazelton Neonatal Behavioural Assessment Scale. The influence of the total maternal dose of pethidine and umbilical cord blood concentration of the drug on such behaviour has been examined with the confounding effects of all other variables controlled. Higher cord blood levels of pethidine were associated with babies who were more prone to respiratory difficulties, drowsy and unresponsive immediately after delivery. Throughout the six weeks in which the assessments were made, depressed attention and social responsiveness were found in infants with high drug levels. At three and six weeks, the infant whose exposure to pethidine had been high tended to change state more frequently, to cry during the test and to be less capable of quieting himself. These findings suggest that the newborn infant responds to pethidine in the same way as the adult, but the changes observed were relatively subtle, and comparison of these infants with a control group whose mothers had received no drugs revealed no between‐group differences in behaviour.

Semen cryopreservation, utilisation and reproductive outcome in men treated for Hodgkin's disease

Between 1978 and 1990, 122 men underwent semen analysis before starting sterilising chemotherapy for Hodgkins disease. Eighty-one (66%) had semen quality within the normal range, 25 were oligospermic (<20×106 sperm per ml) and five were azoospermic (no sperm in the ejaculate). Semen from 115 men was cryopreserved and after a median follow-up time of 10.1 years, 33 men have utilised stored semen (actuarial rate 27%) and nine partners have become pregnant resulting in 11 live births and one termination for foetal malformation. Actuarial 10 year rates of destruction of semen before death or utilisation and death before utilisation are 19% and 13% respectively. This retrospective cohort study demonstrates that approximately one-quarter of men utilising cryopreserved semen after treatment for Hodgkins disease obtain a live birth. The high non-utilisation rate is intriguing and warrants further investigation.

Does elective cryopreservation of all embryos from women at risk of ovarian hyperstimulation syndrome reduce the incidence of the condition

Objectives To analyse the incidence and factors associated with the ovarian hyper‐stimulation syndrome (OHS) in our IVF/GIFT programme before and after the introduction of a strategy to cryopreserve all embryos from women judged to be at risk.