It could be said that the first instance of assisted reproductive technology (ART) was when an eminent surgeon, John Hunter (1728–1793) of London (Figure 1.1), assisted a woman in becoming pregnant by taking a semen sample produced by her husband, who had hypospadias, and inseminating her with that specimen. This was an “assisted conception,” although it is not strictly within the definition of the present-day ARTs, which involve the manipulation of sperm, oocytes and embryos in vitro

Introduction

Sperm preparation methods developed for in-vitro fertilization and embryo transfer (IVF-ET), such as the wash, swim-up and swim-down techniques, and the use of density gradients, have led to a resurgence of interest in intrauterine insemination (IUI). The use of washed prepared sperm for IUI has also resulted in a significant reduction in the side effects associated with the use of neat semen for IUI (which never should be used), such as painful uterine cramps, collapse and infection. In view of the fact that IUI is a relatively simple procedure compared with in-vitro fertilization (IVF), its popularity as a treatment option for certain diagnostic groups of infertile couples is increasing, since it is intermediate between the simpler ovulation induction (OI) and the more “high tech” IVF. This is particularly so in developing countries, where facilities for IVF may be limited and the cost of treatment by IVF is a major issue.

The term “artificial insemination” (AI) covers a range of techniques for insemination: it may be intra-vaginal, intracervical, intrafallopian, intraperitoneal or intrauterine. AI has been used for many years for a number of different indications, and either the husband/partner's sperm (AIH) or donor sperm (AID) may be used. It is almost 200 years since John Hunter advised a man with hypospadias to inject his seminal fluid into his wife's vagina with a syringe, resulting in a normal pregnancy. In the nineteenth century, Sims artificially inseminated six women who had negative postcoital tests. He used their husbands' semen obtained from the vagina after intercourse; one pregnancy was achieved. The first reported case of human donor insemination was by William Pankhurst from Philadelphia in the United States in 1884.

Introduction

Insemination technique has changed greatly during the past 40 years, from a simple vaginal technique that was little different than that used by John Hunter in 1785 to intracervical (ICI), intrauterine (IUI), fallopian tube sperm perfusion (FSP) and direct intraperitoneal insemination (DIPI) techniques. When Nachtigall et al. reviewed the status of artificial insemination in 1979, nearly all inseminations were vaginal and pregnancy rates were generally satisfactory when donor sperm was used or insemination with partner sperm was performed because of physical problems, but very poor when insemination with partner sperm was performed because of low sperm count. The semen specimen was usually fresh for both donor and partner insemination, except in rare cases where multiple samples of poor-quality sperm were cryopreserved in the hope that sufficient “good” sperm would be available when the accumulated specimens were thawed. Those cases were nearly always unsuccessful.

Successful pregnancies following intrauterine insemination of 10 minims (0.6 mL) of fresh unprocessed sperm were reported in 1920, but the procedure was abandoned because of concern about infection. Furthermore, the amount inseminated had to be kept small to reduce uterine cramping, so it was not helpful in cases where the sperm count was low. When insemination techniques were compared in 1957, pregnancy rates for IUI were worse than when the entire sperm specimen was placed in a cervical cup applied to the cervix, or simply deposited in the vagina.

In the present day, insemination with both donor and partner semen is nearly always performed by the intrauterine insemination (IUI) technique.

Introduction

The incidence of female infertility is age- and parity-related. In a national government survey conducted in 2002, 7.4% of all married women in the United States, aged 15–44, reported difficulty becoming pregnant during the previous year. The incidence of infertility ranged from a low of 4% in previously pregnant women aged under 30, to 27% in never-pregnant women aged 40–44. In a previous survey of the same population, 35% of women who sought medical help were treated with ovulation induction (OI), 13% with husband or donor intrauterine insemination (IUI) and 1.7% with in-vitro fertilization (IVF) or other advanced assisted reproductive technology (ART). Similar infertility rates are reported elsewhere in the Western world, with the availability of infertility treatment facilities and the use of IVF varying both between and within countries. In 2003, IVF was responsible for 6.5% of live births in Denmark and 3% of all live births in Europe, compared to 1.2% of live births in the United States. Patients in the United States with private health insurance were four times more likely to receive OI and three times more likely to have IUI than patients without insurance, but no more likely to have IVF than patients without insurance.

The causes of infertility in 14,141 couples, from reports compiled in 1995, were ovulatory disorder 27%, abnormal semen 25%, tubal occlusion 22%, endometriosis 5% and unexplained 17%.

Th is manual is intended for the general or family practitioner, as well as for gynecologists and specialists in infertility treatment. While treatment by in-vitro fertilization (IVF) and other advanced techniques attract the most attention and shape the public perception of infertility treatment, far more infertile couples achieve pregnancies with ovulation induction (OI) or combined ovarian stimulation and intrauterine insemination (IUI), the two techniques described in detail in this book, and which form the first line of infertility treatment. Moreover, they can be performed in almost any office or clinic, thus allowing patients to be treated by physicians and nurses already familiar with their general health, without the need to travel to distant specialty clinics. Many practitioners believe, from their time in training, that evaluation of infertile couples is too time-consuming and unrewarding, and that treatment is too complex to be part of their general or obstetric and gynecological practices. Nothing could be further from the truth. Infertility should be viewed, not as a diagnosis, but as a symptom of an underlying medical problem, affecting either one or both partners, which, if left untreated, will eventually affect their general health and emotional well-being.

Introduction

Use of gonadotropins for ovulation induction (OI) in intrauterine insemination (IUI) cycles increases pregnancy rates per cycle compared to IUI alone or with clomiphene (CC-IUI); however, whether pregnancy rates per couple are increased is less certain. Gonadotropin use for OI may be complicated by multiple pregnancies, particularly triplets and higher orders, and by ovarian hyperstimulation syndrome (OHSS). Their use as first-line treatment should be limited to those women who have hypopituitary or hypothalamic amenorrhea not correctable by other treatment. Gonadotropins should not be used in the treatment of “unexplained infertility” for patients who ovulate, but fail to conceive, until a minimum of three cycles of CC with IUI have been tried first. Gonadotropins should not be used in place of CC because of its anti-estrogen effect on endometrial thickness and cervical mucus before first trying tamoxifen (TMX) 40–60 mg for five days instead of CC. These proscriptions will, if followed, significantly reduce the risk of multiple pregnancy and the risk of OHSS.

The risk of multiple pregnancy is related to the number of preovulatory follicles (more with gonadotropins, fewer with CC and TMX), patient's age and initial cycle of treatment.

Surrogacy

Until recently, women born with severe abnormalities of development of the Müllerian duct system have been unable to have their own genetic children. Adoption or childlessness have been their only options. The introduction of gestational or in vitro fertilization (IVF) surrogacy during the 1990s as a treatment option has changed the prognosis for women in this situation. Now, women with congenital absence or severe malformations of the uterus, or hysterectomy and abnormalities of the uterus incurred as a result of trauma or cancer treatment, have a chance of having their own genetic child, albeit gestated by another woman. As IVF surrogacy has become increasingly acceptable as a treatment option, both to the medical profession and to the general public (British Medical Association, 1996; Bromham, 1992, 1995), these young women can now have their own children, provided, as most of them do, they have normally functioning ovaries. However, some who have survived the treatment of a malignancy in childhood may have lost not only their uterine function, but also their ovarian function. This section reviews the indications for IVF surrogacy and the selection and management of women seeking this treatment, particularly relating to those with congenital abnormalities. The following section discusses the use of egg donation.

Indications

The main indications for considering treatment by IVF surrogacy are:

• congenital absence or abnormality of the uterus

• hysterectomy following malignancy or haemorrhage

• recurrent abortion

• severe medical problems precluding pregnancy and childbirth

• repeated IVF failure.

Congenital absence of the uterus and following hysterectomy are the commonest indications for surrogacy.