Minimizing risk in anonymous egg donation.

Assisted conception carries with it known and putative medical and surgical risks. Exposing healthy women to these risks in order to harvest eggs for donation when a safer alternative exists is morally and ethically unacceptable. Egg sharing minimizes risk and provides a source of eggs for donation. Anonymity protects all parties involved and should not be removed.

Should non-patient volunteers donate eggs?

Egg donation is associated with medical and surgical risks regardless of the source of eggs, be it through commercial, altruistic or more recent egg-share donors. Egg sharing is the only system that does not turn a healthy woman (the donor) into a patient. Using carefully selected egg-share donors, pregnancy rates for both donor and recipient are as good as any egg-donation programme, with one cohort of eggs being used with more efficiency. We propose that anonymous egg sharing, as licensed by the Human Fertilisation and Embryology Authority (HFEA), minimizes risk, is ethically sound and should be considered as the only acceptable form of anonymous egg donation.

Egg-sharing in assisted conception: ethical and practical considerations.

The present acute shortage of eggs for donation cannot be overcome unless adequate guidelines are set to alleviate the anxieties regarding payments, in cash or kind, to donors. The current Human Fertilisation and Embryology Authority (HFEA) guidelines do not allow direct payment to donors but accept the provision of lower cost or free in vitro fertilization (IVF) treatment to women in recognition of oocyte donation to anonymous recipients. Egg-sharing achieved in this way enables two infertile couples to benefit from a single surgical procedure. However, the practical guidelines related to this approach are ill-defined at the present time leading to some justifiable uncertainty. A pilot study was therefore undertaken in order to establish the place of egg-sharing in an assisted conception programme. The current HFEA guidelines on medical screening of patients, counselling, age and rigid anonymity between the donor and recipient were followed. The study involved 55 women (25 donors and 30 recipients) in 73 treatment cycles involving fresh and frozen-thawed embryos. Donors were previous IVF patients who, regardless of their ability to pay, shared their eggs equally with matched anonymous recipients. They paid only for their consultations and tests right up to the point of being matched with a recipient. The sole recipient paid the cost applicable in egg donation of a single egg collection, although both received embryo transfers. The results indicate that although the recipients were older than the donors (41.4 +/- 0.9 versus 31.6 +/- 0.5 years), and there was no difference in the mean number of eggs allocated, the percentage fertilization rates, or the mean number of embryos transferred, there were more births per patient amongst recipients than amongst donors (30 versus 20%). We conclude that providing the donors are selected carefully, this scheme whereby a sub-fertile donor helps a sub-fertile recipient is a very constructive way of solving the problem of the shortage of eggs for donation. There are also the advantages of including a group of women who would otherwise be denied treatment. Problems related to 'patient coercion' can, in our view, be fully overcome by the application of strict common-sense safeguards. The ideal of pure altruism is not without its medical and moral risk. The success of egg-sharing depends on shared interests and a degree of altruism between the donor, the recipient and the centre. The current HFEA guidelines should be applauded for enabling a highly effective concept of mutual help to develop.

Laparoscopic ovarian diathermy: an effective treatment for anti-oestrogen resistant anovulatory infertility in women with the polycystic ovary syndrome.

OBJECTIVE: To determine the long term efficacy of laparoscopic ovarian diathermy in the management of refractory anovulatory infertility in women with the polycystic ovary syndrome. DESIGN: Open study of 50 women treated over a period of 3 years and 3 months, with follow up until 18 months after the last woman was treated. SETTING: Teaching Hospital. SUBJECTS: Fifty consecutive women with refractory anovulatory infertility (mean duration 5.3 (SD 3.5) years). All had been treated unsuccessfully with anti-oestrogens and more than half with gonadotrophins. INTERVENTIONS: Laparoscopic ovarian diathermy. MAIN OUTCOME MEASURES: Ovulatory cycles and pregnancies. RESULTS: Forty-three women (86%) ovulated following ovarian diathermy; the mean time to ovulation was 23 (SD 6.2) days. Three nonresponders ovulated following anti-oestrogen treatment to which they were previously resistant. Thirty-three women have conceived 58 pregnancies; 22 had no treatment other than ovarian diathermy prior to their first post-operative conception; in seven an anti-oestrogen was given because of lengthening cycles; two were treated elsewhere with gonadotrophins without prior postdiathermy anti-oestrogen therapy and conceived; four had the operation repeated and two of these conceived. Twenty-six women conceived within the first 8 post-operative months. Forty-two pregnancies ended in the birth of normal live healthy babies, eight are ongoing and eight miscarried. Of the 22 women who had no pelvic abnormality other than polycystic ovaries, 19 (86%) have had one or more successful pregnancies. CONCLUSION: Laparoscopic ovarian diathermy is a very effective treatment for anti-oestrogen resistant anovulatory infertility in women with the polycystic ovary syndrome and should be considered as the next step in those who fail to respond to anti-oestrogen treatment.

Early experience with in vitro fertilization-embryo transfer and gamete intrafallopian transfer in a Nigerian hospital.

We present our early experience with in vitro fertilisation-embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT) in a Nigerian Hospital. Twenty-one patients were recruited, 11 patients for the IVF-ET program and 10 for the GIFT program. In the IVF program the oocyte recovery rate was 100%, the fertilization rate was 66% and the cleavage rate was 97% but no live pregnancies were achieved. In contrast, one live delivery was achieved with GIFT. These results suggest that both IVT-ET and GIFT are feasible in developing countries.

Laparoscopic ovarian diathermy in the management of anovulatory infertility in women with polycystic ovaries: endocrine changes and clinical outcome.

Twenty-one nulliparous oligomenorrheic women with polycystic ovaries, complaining of infertility (mean duration 6 years) refractory to medical treatment, underwent laparoscopic ovarian diathermy. Eleven had adhesions and/or endometriosis. Regular ovulatory cycles ensued in 17 women (81%). In 9 responders there was a transient rise in mean follicle-stimulating hormone from 5.0 +/- 0.4 (standard error of the mean [SEM]) to 6.7 +/- 0.5 mIU/mL on postoperative day 1 and a fall in testosterone from 2.6 +/- 0.2 to 1.9 +/- 0.2 nmol/L by day 8. Luteinizing hormone fell from 19 +/- 1.2 to 10.4 +/- 1.2 mIU/mL by the follicular phase of the next cycle. Eleven women have conceived 13 pregnancies; 3 miscarried, 7 were delivered at term and 3 are ongoing. Ovarian diathermy is a useful option in women with polycystic ovaries complaining of refractory anovulatory infertility.

One hundred pregnancies after treatment with pulsatile luteinising hormone releasing hormone to induce ovulation.

OBJECTIVE: To review treatment with pulsatile luteinising hormone releasing hormone in infertile women who do not ovulate and are resistant to clomiphene after 100 pregnancies achieved with this treatment. DESIGN: Retrospective analysis of 146 courses of treatment over 434 cycles. SETTING: Infertility clinic. PATIENTS: 118 Women whose failure to ovulate was due to idiopathic hypogonadotrophic hypogonadism (n = 39), amenorrhoea related to low weight (n = 17), organic pituitary disease (n = 15), or polycystic ovaries (n = 47). INTERVENTIONS: Dose of 15 micrograms luteinising hormone releasing hormone/pulse subcutaneously every 90 minutes given with a miniaturised pump throughout cycle monitored by ultrasound. Women with hypogonadotrophic hypogonadism had 48 courses, women with amenorrhoea related to low weight 23, women with organic pituitary disease 18, and women with polycystic ovaries 57. END POINT: Follow up of 100 pregnancies achieved in 77 women during six years after introducing treatment. MEASUREMENTS and main results--One hundred pregnancies (seven multiple, 28 miscarriages). Cumulative rates of pregnancy were 93-100% at six months in women with idiopathic hypogonadotrophic hypogonadism, amenorrhoea related to low weight, and organic pituitary disease. In women with polycystic ovaries (cumulative rate of pregnancy 74%) adverse prognostic factors were obesity, hyperandrogenism, and high luteinising hormone concentrations, which were also associated with a high rate of early pregnancy loss. CONCLUSIONS: Treatment with pulsatile luteinising hormone releasing hormone is safe, simple, and effective, and the preferred method of inducing ovulation in appropriately selected patients. Compared with exogenous gonadotrophin treatment there is little need for monitoring, no danger of hyperstimulation, and a low rate of multiple pregnancies.

Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome.

Women with the polycystic ovary syndrome do not respond well to treatment with luteinising hormone releasing hormone. To determine whether this might be due to an underlying endocrine disturbance basal concentrations of luteinising hormone were measured in 54 infertile women treated with pulsatile luteinising hormone releasing hormone and concentrations at the time of maximum follicular growth were measured in 23 of the patients. Forty one patients ovulated. Forty one patients ovulated and 27 conceived, but nine pregnancies terminated within four weeks after ovulation. Basal luteinising hormone concentrations were significantly lower in those who conceived (12.4 (range 1.3-29.0) IU/l) than in those who did not (19.0 (3.5-50.0) IU/l) and in those whose pregnancy progressed (9.6 (1.3-29.0) IU/l) than in those with early loss of pregnancy (17.9 (7.0-29.0) IU/l). Concentrations at the time of maximum follicular growth were significantly lower in women who ovulated (9.4 (2.9-35.4) IU/l) than in those who did not (29.0 (7.0-50.0) IU/l) and in those who conceived (6.2 (2.9-8.5) IU/l) than in those who did not (17.9 (4.0-50.0) IU/l). These results indicate that high concentrations of luteinising hormone during the follicular phase in women with polycystic ovaries have a deleterious effect on rates of conception and may be a causal factor in early pregnancy loss.

Pulsatile luteinizing hormone-releasing hormone therapy in women with polycystic ovary syndrome.

Induction of ovulation with pulsatile luteinizing hormone-releasing hormone (LH-RH) therapy was attempted in 48 women with polycystic ovary disease (PCOD) and clomiphene citrate (CC) resistant anovulation. Fourteen women ovulated regularly, 23 ovulated variably, but 11 did not ovulate at all. Fifty-two of the 108 cycles of pulsatile LH-RH therapy alone (15 mu gm per pulse, one pulse every 90 minutes) administered through the subcutaneous route were ovulatory. In patients who did not ovulate on subcutaneous LH-RH, treatment with CC (100 mg per day for 5 days) was added to the LH-RH therapy in an additional 33 cycles, of which 21 were ovulatory. In those who did not respond to the combination of treatments, the same dose of LH-RH was administered intravenously: 14 of 29 cycles of intravenous therapy were ovulatory. The overall cumulative conception rate after 6 months of therapy was 60%. When recalculated for ovulatory cycles alone it was 90%, indicating that failure of ovulation was the only cause of the failure of conception. Analysis of the clinical and endocrine findings indicated that failure to ovulate was associated with obesity and hyperandrogenization. Ten of the 23 conceptions ended in miscarriage, 8 within 4 weeks of ovulation. The authors conclude that infertility in patients with PCOD is not optimally corrected by pulsatile LH-RH therapy.

Synergism of pulsatile LHRH therapy with oral clomiphene treatment.

Eighteen anovulatory patients who were resistant to induction of ovulation with clomiphene and with subcutaneous pulsatile LHRH were treated with these two agents given simultaneously. Twelve of the 14 patients with polycystic ovary syndrome, 1 patient with weight-related amenorrhea and 1 of 3 patients with intrinsic pituitary disease responded to the combined treatment. Serial determinations of serum gonadotropin concentrations showed that these remained unchanged by clomiphene treatment, suggesting a direct action on the ovary. For induction of ovulation for in vivo fertilization, the combination of oral clomiphene with subcutaneous pulsatile LHRH is worth trying before proceeding to intravenous LHRH or hMG therapy.

Practical aspects of pulsatile LHRH therapy.

The availability of miniaturized portable infusion devices has enabled the development of another important method of inducing ovulation in women with clomiphene-resistant anovulatory infertility (Labrie et al, 1984; Mason et al, 1984; Armar et al, 1986a). When cases are carefully selected and accurate ultrasound monitoring is used, very impressive conception rates are achieved (Armar et al, 1986a). The treatment is simple, effective and safe.