BRITISH JOURNAL OF ANAESTHESIA

Infertility is a common problem which affects at least one in six couples; 21 % of these are caused by failure of ovulation [1]. Ovarian activity is dependent on the secretion of luteinizing hormone (LH) or follicle-stimulating hormone (FSH) by the pituitary. Normal secretion of these gonadotrophins is controlled by pulsatile release of gonadotrophinreleasing hormone (GnRH) by the hypothalamus. Failure or other abnormalities of release of GnRH or of the secretion of LH or FSH results in disturbances of ovulation. Other causes of infertility include sperm defects, tubal damage, endometriosis, coital failure and defects in cervical mucus. Infertility is unexplained in 28% of cases [1]. Treatment of infertility is determined therefore by the underlying cause. The overall conception rate after 2 yr of treatment in a group of patients with any cause of infertility is 48 % and failure of ovulation can be treated successfully in up to 96% of cases [1]. In 1978, the first in vitro fertilization (IVF) baby was born as a result of an oocyte collected during a natural cycle but the success rate with natural cycles is low. Stimulation of the ovaries to produce numerous oocytes has greatly enhanced the success rate of such techniques and after fertilization allows preservation of surplus frozen embryos for future use. Ovulation may be induced by pharmacological stimulation of the ovary; this causes the development of multiple follicles. This therapy is the basis of treatment of infertility caused by ovulatory failure. IVF and gamete intra-fallopian tube transfer (GIFT) programmes benefit from induction of ovulation by allowing the collection of numerous oocytes, either laparoscopically or by per-vaginal ultrasound techniques. In IVF, fertilization takes place outside the body and the resulting embryos are transferred through the cervix into the uterus where implantation may occur. GIFT, which is appropriate where there are normal fallopian tubes, involves laparoscopic insemination of oocytes with spermatozoa at the end of the fallopian tube where fertilization takes place, allowing the embryo to travel down the tube to implant within the uterus. The regimens used to stimulate ovulation may vary considerably. The simplest form uses cyclical oral therapy in the form of anti-oestrogen drugs, commonly clomiphene citrate but acylofenil or tamoxifen may be used. These anti-oestrogens occupy oestrogen receptors in the hypothalamus thereby increasing the output of pituitary gonadotrophins which stimulate the ovary. More complicated regimens using injectable preparatory gonadotrophins use either pure FSH or a combination of FSH and LH to stimulate follicle development in the ovary. When the follicle has reached a certain size, human chorionic gonadotrophin (HCG) which has primarily a luteinizing action, is given to simulate the LH surge and stimulate final maturation and induce ovulation. The main serious problems with induction of ovulation are increased incidence of multiple births, increased miscarriage rate and the possibility of ovarian hyperstimulation. With the rapid development of assisted reproduction techniques, there is a need for anaesthetists to acquire some basic knowledge of the physiology and principles of treatment of infertility as anaesthetic intervention is often required in the management. General anaesthesia is necessary for GIFT procedures, and sedation or occasionally general anaesthesia for per-vaginal ultrasonic-guided oocyte retrieval. When complications such as ovarian hyperstimulation syndrome (OHSS) occur, anaesthesia is administered for either termination of pregnancy or other surgical interventions that may be necessary. Anaesthetists are also involved in the management of patients with severe OHSS, who should be cared for in an intensive therapy unit. OHSS is the most serious complication of induction of ovulation. It is characterized by marked ovarian enlargement, pleural effusion and ascites [2], and may lead to hypovolaemic shock, renal failure, adult respiratory distress syndrome, thromboembolism, liver dysfunction [3] and cerebrovascular accident [4]. With the increasing use of IVF [5] and associated techniques requiring induction of ovulation, there will be a progressively increasing number of women with this potentially lifethreatening condition. The severity of the condition may be graded according to clinical and ultrasound findings [6]. Grade 1 is a combination of abdominal distension and discomfort; in grade 2 there is in addition nausea, vomiting and/or diarrhoea; in grade 3, ascites is evident ultrasonically; in grade 4, the ascites is clinically evident and difficulty with breathing or pleural effusion may occur; in grade 5 there is clinical hypovolaemia, haemoconcentration, coagulation defects and reduced renal perfusion. The resulting electrolyte imbalance and thromboembolic phenomenon may be life threatening. OHSS usually presents 3-8 days after the administration of HCG and it persists throughout the luteal phase, starting to resolve as menstruation approaches. It occurs more frequently in the younger patient [7], in those with polycystic ovarian syndrome [8] and in cycles where conception sue-