Infertility

What is infertility?

Infertility is usually defined as involuntary failure to conceive after one year of unprotected sexual intercourse. In its wider sense, infertility refers to couples who are having difficulty achieving parenthood and would, therefore, include pregnancy problems such as recurrent miscarriage (Q12.9). Between 80-90% of couples who will achieve a pregnancy without assistance, succeed within the first year of unprotected intercourse and about 95% within two years. The central theme of biology is reproduction, and for those unfortunate couples who have difficulty achieving parenthood there may be feelings including anxiety, frustration and despair.

Primary infertility usually refers to patients with no history of a successful pregnancy. Secondary infertility indicates that there has been a previous successful pregnancy. It may also be appropriate to consider whether the infertility is primary or secondary for each partner as well as for the current partnership.

Infertility is perceived as a disease by less than half of people surveyed (38%), in contrast to the accepted medical opinion; (ii) awareness about the definition and incidence of infertility is relatively low, despite the fact that half of the people polled claimed to know someone affected by infertility.(2000-01)

Related Medical Abstracts

  • Public perception on infertility and its treatment: an international survey. (2000-01)
  • Estimates of human fertility and pregnancy loss (1996)
  • Background pregnancy rates in an infertile population (1996)

How Prevalent Is Infertility?

It has been estimated that one couple in six will have been concerned about their fertility and about 10% of couples are currently experiencing fertility difficulties. In a Danish study of 3,743 randomly selected women aged 15 to 44 years, 27.2% of those planning a family had experienced fertility delays.

Infertility increases with advancing age as indicated by the following two graphs:

 

Both of the line graphs are for women with normal reproductive function, after having unprotected intercourse for one year.

Source: Management of the Infertile Woman by Helen A. Carcio and The Fertility Sourcebook by M. Sara Rosenthal

 

Related Medical Abstracts

  • The epidemiology of infertility in a rural population. (1997-01)
  • Infertility prevalence, needs assessment and purchasing.(1994-01)
  • Infertility-epidemiology and referral practice (1991)

What are the causes of infertility?

The essential requirements for a couple to be fertile are healthy sperm which must be deposited at ejaculation at the cervix, ovaries that are releasing eggs (ovulation), fallopian tubes that are open and healthy and womb capable of nurturing a pregnancy (Figure 9.1).

Infertility

The three most common causes of infertility are:

  • anovulation (eggs are not being released).
  • tubal factor (Fallopian tube disease).
  • male factor infertility (Q9.21.)

Infertility remains unexplained in about 25% of couples following investigations to identify obvious problems in these three areas.

The following graph shows the main causes of infertility in those having IVF in Canada:

Primary Diagnoses for Assisted Reproductive Technology Procedures

 

This chart shows the primary diagnoses responsible for infertility among couples who had an ART (Assisted Reproductive Technology) procedure. Please note that some couples have more than one cause of infertility.

SOURCE: Society for Assisted Reproductive Technology (SART). Statistics quoted are for the year 1995.

Related Medical Abstracts

  • Epidemiological analysis of infertility in a Mexican population (2005-01)
  • Return of fertility in nulliparous women after discontinuation of the intrauterine device: Comparison with women discontinuing otherof contraception (2001)
  • Infertility-epidemiology, aetiology and effective management (1995)
  • Infertility-epidemiology and referral practice (1991-01)
  • Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). (1991-02)
  • Infertility-epidemiology and referral practice (1991)
  • An epidemiological study of 1000 sterile couples]. (1989)
  • Population study of causes, treatment, and outcome of infertility (1985)

What are the objectives of infertility investigations?

The objectives in re questing infertility investigations for you are initially to identify factors that may be contributing to delay in achieving a successful pregnancy and subsequently to monitor your response to treatment.

Folic Acid

Folic acid supplementation may reduce the incidence of spina bifida.

Have there been changes in fertility requirements?

In western society, the survival rate of babies and infants has improved and most couples avoid having large families. Quality of life rather than quantity is the pre-re Quisite. Effective family planning methods, such as the combined oral contraceptive pill, allow modern couples the facility to delay childbearing until socially convenient. In France, the average age of first pregnancy is 28 years compared to 24 years in 1970 and there has been a doubling in the proportion of women giving birth for the first time after 30 years of age since 1972. There was a 25% increase in the number of couples re questing infertility services in the USA from 1982 to 1988. The prevalence of infertility remained unaltered over a ten year period but the proportion seeking medical assistance increased. Furthermore, there has probably been an increase in the number of visits to fertility clinics per couple in association with the increasing number of available treatments. Reproductive medicine is a popular topic, and the media including magazines, newspapers, radio and television serve to inform the public of the advances in medical technology. Only fifty years ago treatment of infertility was relatively primitive. We have now reached a state where even with azospermia (absence of sperm in the man’s semen), it may be possible to aspirate (a needle is introduced into the scrotum) a few sperm and achieve fertilisation by intracytoplasmic sperm injection into the oocytes (eggs – 25).

Related Medical Abstracts

  • Allocating fertility services by medical need (2001-01)
  • Age, the desire to have a child and cumulative pregnancy rate (1997-01)

    What is the effect of age on fertility?

    Fertility declines with advancing female age. The prevalence of infertility reaches 25% in women in their late thirties and there is a rapid decline of fertility after the age of forty. There is also evidence of declining fertility with age in the male partner.

    There is evidence that complications in pregnancy and childbirth increase with advancing maternal age.

    The following graph from Australia shows evidence that women are delaying childbearing:
    The following graph shows the chance of conceiving according to female age in a donor insemination program

    Note that this graph does not specify the number of treatment cycles; the average number of treatment cycles was 6, and the range was 1 to 41

    Hum Reprod. 2001 Nov;16(11):2298-304.

    Related Medical Abstracts

    • The association of age and semen quality in healthy men (2003)
    • The effects of female age on fecundity and pregnancy outcome (2001)
    • Effects of male age on semen quality and fertility: A review of the literature (2001)
    • Human fertility does not decline: Evidence from Sweden. (1999)
    • Age-related decline in fertility: A link to degenerative oocytes? (1997)
    • The impact of the woman’s age on the success of standard and donor in vitro fertilization. (1997)
    • Female age is an important parameter to predict treatment outcome in intracytoplasmic sperm injection. (1996)
    • The age-related decline in female fecundity: a Quantitative controlled study of implanting capacity and survival of individual embryos after in vitro fertilization (1996)
    • Effect of age on sperm fertility potential: Oocyte donation as a model (1996)Delaying childbearing: Effect of age on fecundity and outcome of pregnancy (1991)
  • What is the effect of smoking on fertility?

    Cigarette smoking has an adverse effect on female and male fertility and smoking in pregnancy reduces the future fertility of the unborn child.0601

    Tobacco compounds exert a deleterious effect on the process of ovarian follicle maturation. This effect is expressed by worse in-vitro fertilization parameters in cycles performed on women with smoking habits. Also, uterine receptiveness is significantly altered by the smoking habit. In men, cigarette smoking reduces sperm production. Spermatozoa from smokers have reduced fertilizing capacity, and embryos display lower implantation rates. Even in-utero exposition to tobacco constituents leads to reduced sperm count in adult life. Couples in reproductive age should be strongly discouraged to smoke.0801

    Related Medical Abstracts

    • Cigarette smoking and reproductive function.(2008-01)
    • The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: a review. (2007-01)
    • The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: a review. (2007-02)
    • Early exposure to smoking and future fecundity among Danish twins. (2006-01)
    • Effect of smoking on semen parameters of men attending an infertility clinic. (2006-02)
    • Cigarette smoking is related to a decrease in semen volume in a population of fertile men. (2006-03)
    • What are the epidemiological data on maternal and paternal smoking? (2005-01)
    • Effects of subfertility cause, smoking and body weight on the success rate of IVF. (2005-02)
    • Does cigarette smoking increase time to conception? (2002-01)
    • Cigarette smoking and the risk of male factor subfertility: Minor association between cotinine in seminal plasma and semen morphology (2000-01)
    • Smoking and female infertility: A systematic review and meta-analysis (1998-01)
    • Does cigarette smoking impair natural or assisted fecundity? (1996-01)
    • Reduced fecundability in women with prenatal exposure to cigarette smoking (1989-01)
    • Cigarette smoking associated with delayed conception (1985-01)

      I have fibroids. Could they affect my fertility?

      Fibroids can be found in 50% of women. Many women with several large fibroids conceive without difficulty and go on to have uneventful pregnancies and deliveries. If you are found to have fibroids that are not affecting the cavity of the womb, they probably have no effect on your fertility. Uterine fibroids distorting the uterine cavity, however, may perhaps reduce the chance of pregnancy.

      Related Medical Abstracts

      • The effect of small intramural uterine fibroids on the cumulative outcome of assisted conception. (2006-01)
      • Effect of intramural and subserous myomas on in vitro fertilization cycles and their perinatal results (2006-02)
      • Pregnancy after laparoscopic myomectomy–long-term follow up (2006-03)
      • Effects of the position of fibroids on fertility. (2006-04)
      • Myomas and assisted reproductive technologies: when and how to act? (2006-05)
      • Effect of fibroids on fertility in patients undergoing assisted reproduction. A structured literature review. (2005-01)
      • Pregnancy after uterine artery embolization for leiomyomata: the Ontario multicenter trial. (2005-02)
      • Fibroids and in-vitro fertilization: which comes first? (2005-03)
      • Hysteroscopic management in submucous fibroids to improve fertility. (2005-04)
      • Impact of subserosal and intramural uterine fibroids that do not distort the endometrial cavity on the outcome of in vitro fertilization-intracytoplasmic sperm injection. (2004-01)
      • Effect of uterine leiomyomata on the results of in-vitro fertilization treatment (1995)

      Fibroids – Treatment

      Fibroids become more common in the later years of reproductive life (15). The relationship between fibroids and infertility has been the subject of debate. Implantation and pregnancy rates have been found to be reduced only when the fibroids are distorting the endometrial cavity (submucous fibroids). Until recently, the only treatment was myomectomy at laparotomy. Developments with minimally invasive surgery and in particular transcervical hysteroscopy allow resection of submucous fibroids. Controlled trials are required to establish the benefits.

      Related Medical Abstracts

      • Myomectomy: A retrospective study to examine reproductive performance before and after surgery. (1999)
      • Abdominal myomectomy for infertility: A comprehensive review. (1998)

      I was born with an abnormal uterus. Could this affect my fertility?

      During investigation of infertility, ultrasound examination or hysterosalpingography (Q9.20 ) may demonstrate a congenital abnormality of your womb (Q3.3 ). Many women with these abnormalities achieve pregnancy without difficulty and go on to have healthy babies.

      Related Medical Abstracts

      What is the relationship between endometriosis and infertility?

      <pstyle=”text-align: justify;;=”” margin-top:5pt;=”” margin-bottom:5pt”=””>At times, tissue similar to the endometrium (lining of the uterus) may be found at other sites and this is called endometriosis.

      Severe endometriosis is uncommon but undoubtedly it may damage the Fallopian tubes and ovaries resulting in infertility. The significance of milder forms of endometriosis as a cause of infertility, however, has been the subject of debate.

      Endometriosis has been reported to be more common in infertile women although it is difficult to be certain because estimating the incidence of endometriosis in the general population must be subject to inaccuracy as the diagnosis requires an invasive procedure.

      In women with primary infertility, mild endometriosis is more common when there is a male factor problems, suggesting that, in these women, infertility predisposes to endometriosis rather than the endometriosis being a cause for the infertility.

      Mild endometriosis is extremely common: with scrutiny and appreciation of the various forms of lesions it can probably be found, at least intermittently, in the majority of women so that it should no longer be considered a pathological (disease) state. Treatment of mild endometriosis confers no improvement in pregnancy rates.

      Related Medical Abstracts

      • Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility (1998)
      • Using economics alongside medical audit. A case study of the management of endometriosis (1996)
      • Buserelin acetate versus expectant management in the treatment of infertility associated with minimal or mild endometriosis: A randomized clinical trial (1992)
      • The impact of treatment on the natural history of endometriosis (1990)
      • The relationship between endometriosis and semen analysis: A review of 490 consecutive laparoscopies (1989)
      • Successful treatment of asymptomatic endometriosis: does it benefit infertile women? (1987)

      Endometriosis – Treatment

      Mild endometriosis does not seem to be a factor in infertility and randomised trials (placebo and controlled trials) comparing medical treatments including danazol, gestrinone, medroxyprogesterone acetate and GnRH analogues with controls have shown no advantage in terms of pregnancy rates.

      When there is severe endometriosis, pregnancy rates of 50% have been achieved following restoration of normal anatomy at laparotomy and similar success rates may be possible with minimally-invasive surgery.

      After the FLUSH trial: a prospective observational study of lipiodol flushing as an innovative treatment for unexplained and endometriosis-related infertility.(2006-01)

      Can a cervical erosion or cervicitis impair fertility?

      Cervicitis and cervical ectopy ( cervical erosion) are frequently found at the time of taking a cervical smear test. There is no evidence that either reduce fertility.

      Can a retroverted uterus cause infertility?

      About one lady in five has a womb that tilts backwards (27 ). At one time it was believed that a retroverted womb was associated with virtually every kind of gynaecological symptom, including infertility, and an operation called ventrosuspension was performed to tilt the womb forward. It is now recognised that women with retroverted wombs are no less fertile than those with an anteverted (forward tilting) uterus and surgery is not beneficial.

      How does a previous ectopic pregnancy affect fertility?

      A history of ectopic pregnancy would increase your chance of infertility in the future. If you do conceive there is a one in thirty chance of another ectopic pregnancy. It would be advisable for you to have a series of ultrasound scans in your next pregnancy to check that this time the pregnancy is within the uterus.

      Related Medical Abstracts

      • Survival analysis of fertility after ectopic pregnancy (2001)
      • Ectopic pregnancy and infertility following treatment of infertile couples: A follow-up of 929 cases (1991)

        When should we seek advice about our infertility?

        Your general practitioner will be able to advise you and may be able to initiate infertility investigation. The results may influence how you proceed. Infertility investigations are usually commenced if pregnancy has not occurred within a year.

        It would be appropriate to commence infertility investigations and treatment earlier if you have an abnormal menstrual cycle, a history suggesting possible tubal disease, coital difficulties or if you have had infertility problems before.

        A semen test would indicate if there is a male factor to the infertility.

        Rubella

        Rubella (German Measles), which can damage the fetus in pregnancy, is avoidable by ensuring adequate immunity and infertility investigation provides us with an opportunity to ensure that you are immune. If a blood test shows that you have inadequate immunity, your general practitioner will arrange for you to be immunised.

        How can the cause of infertility be determined?

        Initially your doctor will wish to obtain a full history of the problem, examine you and start some investigations. (Figure 09-02) is a flowchart outlining how infertility can be investigated and treated.

        Infertility Investigation
        Infertility Investigation

        Figure 9.2 Investigation of Infertility

        Related Medical Abstracts

        Figure9.2 is a flowchart outlining how infertility can be investigated and treated.

        • Optimal use of infertility diagnostic tests and treatments. (2000)
        • Practice patterns among reproductive endocrinologists: Further aspects of the infertility evaluation (1998)

        Hostile Cervical Mucus

        Hostile cervical mucus may be more acidic than normal. Treatment with sodium bicarbonate (a level teaspoonful dissolved in half a pint of lukewarm water), and 40ml of the solution introduced into the vagina with a syringe about two hours before coitus, can significantly improve pregnancy rates. Oestrogens (e.g. Premarin 0.625) have been administered in the preovulatory phase from day 9 to day 13 of the menstrual cycle for cervical mucus factor infertility. Mucus hostility may be associated with antibodies being produced against sperm. At one time, sperm antibody tests were arranged and steroids administered if the results were positive. Steroid treatment has some dangers and these days artificial insemination (23) or IVF seem more appropriate.

        Related Medical Abstracts

        • Exogenous estrogen therapy for treatment of clomiphenecitrate-induced cervical mucus abnormalities: Is it effective? (1990)

IVF – In Vitro Fertilization (UK Fertilisation)

IVF literally means fertilisation outside the body. IVF was initially developed for women who had severe tubal disease or who had their Fallopian tubes removed but this treatment has also proved successful for unexplained infertility and male factor infertility. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed. A typical IVF treatment cycle is outlined in (Figure 10.3). Originally, eggs were collected laparoscopically (laparoscopy) but we now collect the eggs by ultrasound guidance usually through the vagina.

Please see

IVF – In Vitro Fertilisation (UK)

or

IVF – In Vitro Fertilization (USA)

Intracytoplasmic Sperm Injection (ICSI)

If there is severe male factor infertility or previous IVF with failure to fertilise, one sperm can be injected into each egg – intracytoplasmic sperm injection (ICSI) to increase the chance of success (Figure 10.4).9.2

is a flowchart outlining how infertility can be investigated and treated.

 

ICSI -Intracytoplasmic Sperm Injection

Figure 10.4 ICSI – Intracytoplasmic Sperm Injection

Some women are unable to produce healthy eggs either because they have reached their menopause early, they are approaching their menopause (Figure 10.7) or because their eggs carry abnormal genes. The only realistic chance of a successful pregnancy in these circumstances is if another woman donates some of her eggs. There are some remarkable women who, for altruistic reasons, come forward voluntarily and go through the regimen for IVF egg collection and donation. Egg donors should usually be aged 35 years or less.

Figure 10.7

The demand for egg donation greatly exceeds supplies. There are many women who have healthy eggs and need IVF but for economic reasons IVF is beyond them. The combined requirements of funding for IVF for the less privileged and of others for egg donors has led to the development of eggs sharing. If a woman requiring egg donation will fund the two treatments, she may receive perhaps half the eggs provided by the woman who hasQuality eggs but cannot afford the treatment.

Some women are unable to produce healthy eggs either because they have reached their menopause early, they are approaching their menopause (Figure 10.7) or because their eggs carry abnormal genes. The only realistic chance of a successful pregnancy in these circumstances is if another woman donates some of her eggs. There are some remarkable women who, for altruistic reasons, come forward voluntarily and go through the regimen for IVF egg collection and donation. Egg donors should usually be aged 35 years or less.

Selective Embryo Transfer

Selective embryo transfer is becoming an option for couples at risk of transmitting an inherited disorder. The embryos are produced by standard IVF techniques. One or two cells are removed (embryo biopsy) from the 6-10 cell embryo and evaluated for the disorder. Only embryos shown to be free of the disorder are transferred into the uterus. Although 25% of the early embryonic cells are removed, the remaining cells have been shown to survive and produce perfectly healthy babies.

The technological advances in IVF such as selective embryo transfer open up potentially serious ethical issues. It is technically possible, for example, to determine the sex of the embryos, which leads to sex selection. A couple may have several boys but no girls and some seek IVF with sex selection. Technically, IVF with embryo selection according to sex is possible although this is a difficult ethical issue that has already engendered debate in the medical literature. Most of us working with infertility feel unhappy about the concept of selection for non-medical reasons but society will have to address this option in time. In the UK it is illegal to undertake sex selection.

Tubal Surgery and IVF Compared

Information about success rates is essential for couples to make informed decisions. In vitro fertilization (IVF) provides an alternative to tubal surgery. For mild tubal disease and previous sterilisation, tubal surgery is probably the treatment of first choice. With severe tubal disease, IVF carries the better success rate. For intermediate disease, the optimum method in terms of success is less certain. IVF is becoming increasingly successful (Figure 10.5) and appropriately more popular (Figure 10.6).

Figure 10.5

Figure 10.6

The merits of tubal surgery and assisted reproduction (Assisted Reproductive Technology ART) need careful comparison. In-vitro fertilisation is becoming more readily available with a corresponding reduction in the use of tubal surgery.

IVF is associated with a higher incidence of multiple pregnancy. Perinatal mortality rates following assisted conception procedures are treble that of spontaneous conception although most of the increase is related to multiple pregnancy. There is a five-fold increase in perinatal mortality (stillbirths and first week losses) with triplets compared with singletons. The predicted costs associated with delivery of each baby for a singleton pregnancy in the USA in 1991 was $9,845, for a twin pregnancy $18,974 and for triplets $36,588. Between 1986 and 1991, assisted reproduction techniques were found to be responsible for 35% of twins and 77% of higher order pregnancies.

In the NHS only about 25% of purchasing authorities are currently supporting IVF treatment and the number is falling. There can be little doubt, that from a purely economic point of view, a greater number of pregnancies could be achieved with a given amount of funding using low tech treatments. Many couples would prefer tubal surgery in the first instance and the opportunity to conceive naturally, only resorting to IVF if this fails.

Failed Infertility Treatment

Although there have been tremendous advances in the treatment of infertility, it is a matter of frustration for all concerned that a successful outcome cannot be guaranteed. Sometimes with IVF, fertilisation failure may occur and this could explain for the couple concerned why other treatments have been unsuccessful. The majority of human embryos are lost as a result of implantation failure and any treatment that may reduce this problem would be a major advance in infertility treatment. Low dose aspirin (75 mg daily) improves pregnancy rates in patients with increased antiphospholipid antibody (Q12.17).

It may be difficult to know how long to continue with your infertility treatment. Sometimes a counsellor may provide assistance. It can be particularly difficult if one partner is keen to continue and the other is not. There are times in life when it is helpful to have a plan. You may, for example, decide that you will continue for another six months or a year and then stop. One of the difficulties for you will be that inevitably, with current rates of progress, you may live in hope that a new treatment will prove effective. The medical profession never gives up and is always seeking to improve. Rest assured that however busy your carers may be, they will always have your best interests at heart and they will share with you in any success as well as failures.

Infertility Treatment and Stress

Inevitably the longer people try for a baby the greater the stress that they endure. Friends and family seem to produce babies without difficulty and the media highlight happy couples with their families. There has been quite a lot of research in this area. Surprisingly, no consistent relationship between stress and fertility has been found.

  • The fertility problem inventory: Measuring perceived infertility-related stress. (1999)
  • Distress and reduced fertility: A follow-up study of first-pregnancy planners.(1999)
  • The experiences of couples who have had infertility treatment in the United Kingdom: Results of a survey performed in 1997. (1999)

Finding the best fertility and IVF Unit

Society and purchasers, in all walks of life, are being trained to believe in effectiveness measurements often using arbitrary league tables. The success rates of infertility treatments are difficult to compare as there is a variety of factors associated with infertility with couples having a spectrum of severity. These factors include:

  • age of each partner.
  • cause of the infertility.
  • duration of infertility.
  • previous treatments.

There is a rapidly increasing number of treatments and a variety of protocols for each treatment. Finally, success may be reported in terms of biochemical pregnancy (a positive pregnancy test that may be performed between 9 and 21 days after the possible conception day), clinical pregnancy (evidence of a viable pregnancy on early ultrasound), ongoing pregnancy, and live births. Live birth rates may overstate success as this may include multiple births.

These problems are well recognised and useful attempts to satisfy the need for an overview have been made. Whilst high-tech assisted conception techniques may provide higher success rates per cycle, they are completely unnatural and highly invasive. Furthermore, assisted conception has a high incidence of multiple pregnancies that are prone to obstetric and neonatal complications.

We believe that couples must be provided with unbiased information so that they can, as far as economic restrictions allow, follow the treatment path of their choice. There is a need for better organisation and integration of resources to ensure that simple, less invasive and more economical investigations and treatments are fully utilised before resorting to ‘high-tech’ options simply because they may be more modern and receive wider media coverage.

In the UK, HFEA provides details of the results for all IVF Units.

Finally, when choosing a fertility unit, it should be remembered that whereas ultimate success is a fundamental objective, the care provided by the fertility team is important and you may find that your general practitioner, friends or family are able to advise you.

Comparison of success rates is extremely difficult as different units may have varying exclusion policies. The Human Fertilisation and Embryology Authority (HFEA) allows for adverse factors that could influence the results of the British assisted conception units by providing an adjusted live birth rate.

Comparing Infertility Treatments

When comparing outcomes of various infertility treatments, we must make allowance for a variety of confounding factors. Couples seeking infertility treatment are likely to be slightly older and this confers a negative bias. Those who follow all possible treatment options including IVF tend to be educated and of higher socio-economic status and these confer a more positive influence. Treatment regimens using ovulation induction drugs and particularly gonadotrophins, are more likely to result in multiple pregnancy resulting in a higher birth rate but greater obstetric (childbirth) risks.

Results reported from individual departments are more likely to be from pioneers or those achieving the best results. National statistics and meta-analyses (Q33.23) indicate a more appropriate reflection of the situation. Treatment advances are occurring so frequently that trends are difficult to interpret. Intracytoplasmic sperm injection (ICSI – 25), for example, has resulted in a fall in donor insemination treatment cycles.

Are Infertility Treatments Improving?

New effective treatments arrive almost yearly. Some, such as mletrozole (12A) are surprisingly simple to use and cost very little whereas others like ICSI (25) are extremely complex and expensive.

Until the 1960s treatment options were very limited. Anovulatory infertility (Q9.17) has only been treatable by drugs since the early 1960s; success rates from medication are high. If investigation showed evidence of blocked Fallopian tubes, surgery may prove successful for between ten and twenty percent. If there was evidence of severe male infertility, donor insemination was a possibility; until the last few years no more than 2% of men with severe infertility problems could be treated by other means. The arrival of IVF twenty years ago and the subsequent development of ICSI seven years ago have changed the picture completely now only 2% of couples with severe male factor infertility cannot be treated. Cryopreservation (freezing for storage and later thawing and utilisation) of embryos and ova, and embryo biopsy (28) are remarkable technical achievements that merit consideration. The latest development involves culturing the embryos for five days to the blastocyst stage. Implantation of blastocysts provides higher implantation rates than with embryo transfer at two days. It is hoped that eventually only one embryo will be transferred on the fifth day with a 70% chance of an ongoing pregnancy. Each development requires scientific analysis and raises difficult ethical questions.

Sadly, a successful outcome from infertility treatment cannot be guaranteed. Even with IVF there is only an average 20% success rate per cycle or about 50% with three treatment cycles. The emotional toll during treatment cycles cannot be adequately estimated and, when there is failure, devastation and at times despair are inevitable. Some couples will give up relatively early. For others parenthood seems their only purpose in life and they travel the world seeking success.

The latest data from the USA shows that

Overall, 42% of ART transfer procedures resulted in a pregnancy, and 35% resulted in a live-birth delivery (delivery of one or more live-born infants).2006-01In the 1990s typical pregnancy rates were in the order of 20%.

A couple I have known for many years were found to have male factor infertility. They chose to wait for a miracle rather than accept AID (23). Now aged fifty the lady poured her heart out to me. The miracle never happened. For this couple, developments including ICSI have come too late. I explained that even if they had elected to pursue donor insemination, success would not have been guaranteed but they are left with an empty feeling, as they never tried.

For those unfortunate couples who do not meet with success from treatment they will at least know that they tried although it was not to be. There may be an option for them to pursue adoption.

  • Assisted reproductive technology surveillance–United States, 2003. (2006-01)
  • Comparison of blastocyst transfer to day 3 transfer with assisted hatching in the older patient. (2002)
  • Blastocyst transfer for patients with multiple assisted reproduction treatment failures: Preliminary experience (2001)
  • The Human Rights Act (1998) and its impact on reproductive issues (2001).?
  • Blastocyst culture: toward single embryo transfers. (2000)
  • Assisted hatching increases the implantation and pregnancy rate of in vitro fertilization (IVF)-embryo transfer (ET), but not that of IVF-tubal ET in patients with repeated IVF failures (1997)
  • Salpingectomy improves the pregnancy rate in in-vitro fertilization patients with hydrosalpinx (1996)?
  • High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin (1994)
  • Five decades of progress in management of the infertile couple (1994)?
  • Assisted hatching in the treatment of poor prognosis in vitro fertilization candidates (1994)

Infertility Treatment and the risk of miscarriage

Miscarriage (Miscarriage) is estimated to occur in between 10 and 20% of pregnancies. A meta-analysis of assisted conception found a spontaneous miscarriage incidence of 22%. In a study in Ireland the outcome of pregnancies achieved by IVF were compared to those conceived spontaneously whilst awaiting treatment. There were 16.5% miscarriages in the IVF group compared to 5% in the spontaneous pregnancy group. The psychological effects of miscarriage following infertility treatment cannot be underestimated. There is evidence that 50% of male partners suffer significant disturbance.

Obese and underweight women have an increased risk of miscarriage, and hormonally substituted frozen embryo transfer is associated with an even higher miscarriage rate.0801

  • High and low BMI increase the risk of miscarriage after IVF/ICSI and FET.(2008-01)
  • Incidence of spontaneous abortion among pregnancies produced by assisted reproductive technology. (2004-01)
  • The lived experience of miscarriage after infertility. (2003-01)
  • Polycystic ovarian syndrome and the risk of spontaneous abortion following assisted reproductive technology treatment. (2001-01)
  • Pregnancy and miscarriage rates in 3978 donor insemination cycles: effect of age, parity and partner’s infertility status on pregnancy outcome. (2000-01)
  • Course and outcome of IVF pregnancies and spontaneous conceptions within an IVF setting (1995)
  • Incidence of fetal loss in infertility patients after detection of fetal heart activity with early transvaginal ultrasound (1993)

Infertility Treatment and the risk of ectopic pregnancy

Disorders of the Fallopian tube are more common in women with reduced fertility and there is an increased risk of ectopic pregnancy in those with a history of infertility. Even when embryos are transferred into the uterine cavity following IVF there is still a 4.5% chance of an ectopic compared to 1% in the general population.

  • Risk factors for ectopic pregnancy: a case-control study. (2006-01)
  • Ectopic Pregnancy Risk With Assisted Reproductive Technology Procedures (2006-02)
  • Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France. (2003-01)
  • Risk factors for ectopic pregnancy in assisted reproduction. (1999-01)

What is a heterotopic pregnancy and is it related to infertility treatment?

This is a multiple pregnancy with one embryo implanting in the uterine cavity and another is simultaneously ectopic. The natural incidence of heterotopic pregnancy is one in 30, 000. Infertility is associated with an increased risk of ectopic pregnancy and infertility treatment involving ovulation induction drugs increases the chance of multiple pregnancy. As a result of assisted conception, the incidence of heterotopic pregnancy has increased.

Ultrasound can assist early diagnosis of heterotopic pregnancy. In one study, two-thirds of the intrauterine pregnancies resulted in live births.

  • A comparison of heterotopic and intrauterine-only pregnancy outcomes after assisted reproductive technologies in the United States from 1999 to 2002. (2006-01)
  • Heterotopic pregnancy (2006-02)
  • Heterotopic pregnancy: two cases and a comparative review. (2006-03)
  • Ruptured heterotopic pregnancy with successful obstetrical outcome: a case report and review of the literature. (2005-01)
  • Heterotopic pregnancy after in vitro fertilization-embryo transfer. (2004-01)

Infertility and Multiple Pregnancy – The Risks

Infertility treatments involving ovulation induction are associated with an increased incidence of twins and higher order multiple pregnancy . The natural incidence of twins is one in eighty pregnancies and for triplets it is one in six thousand. Ovulation induction alone increases the incidence of twins four-fold. A study of twenty-four thousand IVF pregnancies found a 25-fold increase in the incidence of twins and a 350-fold increase in triplets.

zz

Figure 11.1

Multiple pregnancy is regarded as ‘high-risk’ in obstetrics as all the potential complications of pregnancy occur more frequently. These include maternal problems such as anaemia, urinary tract infection, high blood pressure and bleeding. Miscarriage, premature delivery, poor placental function reducing the growth rate of the babies, perinatal mortality (stillbirths and babies dying in their first week) are all more frequent in twins. These problems are disproportionately more likely to occur with higher order pregnancies (Figure 11.2).

Figure 11.2

  • Preterm birth in twins after subfertility treatment: population based cohort study. (2005-01)
  • Perinatal outcomes of in vitro fertilization twins: a systematic review and meta-analyses. (2005-02)
  • The risk of mortality or cerebral palsy in twins: a collaborative population-based study. (2002-01)
  • Comparison of risk factors for cerebral palsy in twins and singletons. (2002-02)
  • Assisted reproductive technologies: Estimates of their contribution to multiple births and newborn hospital days in the United States (1996)
  • Perinatal outcome of twin pregnancies obtained after in vitro fertilization: Comparison with twin pregnancies obtained spontaneously or after ovarian stimulation (1996)
  • Perinatal outcome of triplet pregnancies following assisted reproduction (1994)
  • Triplets and quadruplets born in Victoria between 1982 and 1990: The impact of IVF and GIFT on rising birthrates (1993)
  • Outcome of twin, triplet, and quadruplet in vitro fertilization pregnancies: The Norfolk experience (1992)
  • Births in Israel resulting from in-vitro fertilization/embryo transfer, 1982-1989: National registry of the Israeli association for fertility research (1992)

Selective Termination of Pregnancy

Most pregnancies with three early gestation sacs (each sac usually contains one embryo) reduce spontaneously. In one study, there were 38 pregnancies with three gestation sacs between three and four weeks after IVF/embryo transfer. At delivery there were seven single babies, twelve twins and eighteen sets of triplets.

Selective termination is a procedure usually employed when one fetus is found to have a significant abnormality with the objective of allowing the pregnancy to continue with the expectation of delivery of the remaining healthy infant(s). Multifetal pregnancy reduction is the termination of one or more seemingly healthy fetuses with the objective of reducing the risks of higher order multiple pregnancies. Recent analysis of data from North East London showed that the neonatal death rate (babies dying in the first four weeks per 1000 live births) for a singleton pregnancy is 3.4, for twins 25.4 and for higher order it is 93.8. Multifetal pregnancy reduction has been shown to improve the perinatal outcome for pregnancy with four or more fetuses, although there is a 9% risk of losing the entire pregnancy.

The ethical issues associated with selective termination of a fetus with significant abnormality are identical to those pertaining when there is only one fetus. The ethical issues relating to multifetal pregnancy reduction are far more complex as it involves the sacrifice of one or more normal fetuses for the benefit of the remainder. Interestingly, a psychological assessment of surviving offspring and their parents in Holland found no adverse effects.

    • Information-sharing among couples considering multifetal pregnancy reduction. (2007-01)
  • Risks of miscarriage and early preterm birth in trichorionic triplet pregnancies with embryo reduction versus expectant management: new data and systematic review. (2006-01)
  • Lived experiences of Taiwanese women with multifetal pregnancies who receive fetal reduction. (2006-02)
  • Two hundred ninety consecutive cases of multifetal pregnancy reduction: comparison of the transabdominal versus the transvaginal approach. (2004-01)
  • Embryo reduction versus expectant management in triplet pregnancies. (2004-02)
  • Obstetric outcome and psychological follow-up of pregnancies after embryo reduction. (1999-01)
  • Multifetal reduction increases the risk of preterm delivery and fetal growth restriction in twins: A case-control study (1997)
  • Psychological reactions after multifetal pregnancy reduction: A 2-year follow-up study (1997)
  • The current status of multifetal pregnancy reduction (1996)
  • Pregnancy outcome after multifetal pregnancy reduction to twins compared with spontaneously conceived twins (1996)
  • Follow-up of pregnancies, infants, and families after multifetal pregnancy reduction (1994)
  • Improved results in multifetal pregnancy reduction: A report of 72 cases (1994)

How can the pregnancy risks following infertility treatment be reduced?

The greatest risks are associated with multiple pregnancy and this is largely dependent on the use of ovulation induction agents (4). A common reason for anovulation is PCOS (Q7.2) and ovulation induction agents have frequently been employed. The arrival of metformin as an effective treatment that reverses the underlying cause of PCOS may reduce the need for ovulation induction.

IVF is associated with increased incidence of multiple pregnancy. The success of IVF has given it an element of glamour. Ultimately it is a matter of patient choice but it is my own view that there is a place for fully exhausting lower-tech treatments before resorting to IVF. Fertility units are compared by their pregnancy rates and ‘take-home’ baby rates. There is an understandable temptation to put back as many embryos as possible to achieve positive results (Figure 11.1). Those of us who are involved in the care of the resultant pregnancies see the joys of successful outcomes but our views are chastened when we see things go wrong (see Q11.8). In the UK, the number of embryos that can be transferred into the uterus has been limited to three and there is current debate suggesting that we should further reduce to two. This is a move that many of us obstetricians would favour.

There is an advantage in pregnancies following infertility treatment being cared for by a team with a special interest in this area. Whilst I have no doubt that even greater vigilance is given in the care provided for pregnancies resulting from infertility treatment, there is evidence that successful outcomes occur slightly less frequently when compared with pregnancies achieved naturally. Doctors in general, and obstetricians in particular, are better placed than most to contemplate the miracles of nature. We do not intervene unless we believe that there is a definite advantage. When a pregnancy reaches term, there is no advantage for the baby to await events or to experience passage through the birth canal. An increasing proportion of women who have experienced infertility elect to be delivered by caesarean section.

There is a perceptible pressure to reduce obstetric intervention albeit mainly from those who have not experienced the occasional downside of natural childbirth. For those women who have experienced prolonged infertility and successful treatment, natural childbirth may seem less important than for others. There is an element of risk in every aspect of our lives and sadly there are times when even particularly precious pregnancies go wrong at the last moment. Usually, although not always, it is an unavoidable event of nature.

  • A two- versus three-embryo transfer: The oocyte donation model (2001)
  • Obstetric and perinatal outcome of pregnancies after intrauterine insemination. (1999)
  • Obstetric outcome in 232 ovum donation pregnancies. (1998)
  • Triplets and embryo transfer policy. (1997)
  • The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence (1994)

If we have infertility treatment, will our baby be healthy?

In spontaneous conception, the one follicle that has become dominant that cycle is fertilised by the sperm that has beaten all the others in a race. There have been millions of sperm released during the ejaculation. The concept of natural selection is dependent on the idea that the fittest survive. Infertility treatment, particularly IVF, ICSI and cryopreservation circumvent natural selection. There has been understandable concern that these infertility treatments may be associated with an increased risk of congenital abnormality. Reassuringly, however, results reported from around the world indicate that there is no major increase in the rate of babies being born with abnormality.

  • Follow-up of children born after ICSI. (2002)
  • Outcome and follow-up of children born after IVF-surrogacy (2001)
  • Pregnancy and child outcome after oocyte donation (2001)
  • Follow-up studies of children born after frozen sperm donation (2001)
  • Review: Parent-child relationships and child development in donor insemination families (2001)
  • Health of 227 children born after controlled ovarian stimulation for in vitro fertilization using the luteinizing hormone-releasing hormone antagonist cetrorelix (2001)
  • Obstetric outcome and follow-up of children born after in vitro fertilization (IVF) (2000)
  • Incidence of congenital malformations in children born after ICSI. (2000)information?
  • The psychological status at school age of children conceived by in-vitro fertilization. (1999)
  • Infants conceived using in-vitro fertilization do not over-utilize health care resources after the neonatal period. (1998)
  • Stigma, disclosure, and family functioning among parents of children conceived through donor insemination (1997)
  • Follow-up of a cohort of 422 children aged 6 to 13 years conceived by in vitro fertilization (1997)
  • Donor insemination: Child development and family functioning in lesbian mother families (1997)
  • Obstetric and perinatal outcome of pregnancies following intracytoplasmic sperm injection (1996)
  • Intelligence and behaviour in children born after in-vitro fertilization treatment (1996)
  • Growth and physical outcome of children conceived by in vitro fertilization (1996)
  • Assisted reproduction: A reassuring picture (1996)
  • The European study of assisted reproduction families: Family functioning and child development (1996)
  • Pregnancy outcome following exposure to gonadotrophin-releasing hormone analogue during early pregnancy: Comparisons in patients with normal or elevated luteinizing hormone (1995)
  • Outcome in children from cryopreserved embryos (1995)
  • Birth characteristics and perinatal outcome of babies conceived from cryopreserved embryos (1994)
  • A controlled study of the psycho-social development of children conceived following insemination with donor semen (1993)
  • Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer (1991)
  • Perinatal outcome and congenital malformations in in-vitro fertilization babies from the Bourn-Hallam group (1991)

What are the psychological effects of infertility treatment?

For those who have difficulty achieving parenthood, there is a feeling of unhappiness and reduced well-being. There are studies that confirm that infertile women in particular are particularly prone to psychological disturbance after long-term infertility. Anxiety, depression, a variety of health complaints and lack of self-esteem are more prevalent and may require support counselling and even supportive psychotherapy. Men do not escape psychological disturbance although this is more often repressed but subsequently leads to greater risk of psychosomatic illness (2).

  • Life after infertility treatment: A long-term investigation of marital and sexual function. (1998)information?
  • Psychological consequences of having triplets: A 4-year follow-up study (1997)information?
  • Facing the unacceptable: The emotional response to infertility (1997)information?
  • Long-term infertile couples: A study of their well-being (1993)information?
  • Quality of parenting in families created by the new reproductive technologies: A brief report of preliminary findings (1993)information?
  • The impact of infertility on psychological functioning (1992)information?
  • Successful parents of in vitro fertilization (IVF): The social repercussions (1992)

Comparing Infertility Units

  • How do patients choose private in vitro fertilization treatment? A customer survey in a tertiary fertility center in the United Kingdom (2001)
  • Profiling assisted reproductive technology: Outcomes and quality of infertility management. (1998)

Comparing Infertility Treatments

When comparing outcomes of various infertility treatments, we must make allowance for a variety of confounding factors. Couples seeking infertility treatment are likely to be slightly older and this confers a negative bias. Those who follow all possible treatment options including IVF tend to be educated and of higher socio-economic status and these confer a more positive influence. Treatment regimens using ovulation induction drugs and particularly gonadotrophins, are more likely to result in multiple pregnancy resulting in a higher birth rate but greater obstetric (childbirth) risks.

Results reported from individual departments are more likely to be from pioneers or those achieving the best results. National statistics and meta-analyses (Q33.23) indicate a more appropriate reflection of the situation. Treatment advances are occurring so frequently that trends are difficult to interpret. Intracytoplasmic sperm injection (ICSI – 25), for example, has resulted in a fall in donor insemination treatment cycles.

  • Cost-effective treatment of the infertile couple (1998)
  • Reliability of league tables of in vitro fertilisation clinics: Retrospective analysis of live birth rates. (1998)

Internet Use by Infertile Couples

  • Use of the Internet by infertile couples.

How successful is infertility treatment?

  • Assisted reproductive technology in Europe, 2002. Results generated from European registers by ESHRE. (2006-01)
  • Intra-uterine insemination for unexplained subfertility.(2006-02)
  • A new era in ovulation induction.(2006-03)
  • Letrozole induction of ovulation in women with clomiphene citrate-resistant polycystic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle-stimulating hormone ratio.(2006-04)
  • Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. (2006-05)
  • Clomiphene citrate–end of an era? A mini-review. (2005-01)
  • Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination. (2004-01)
  • Case series of a single centre’s treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination in 2002. (2004-02)
  • Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study. (2002)
  • Assisted reproductive technology in Europe, 1997. Results generated from European registers by ESHRE (2001)
  • Effective treatment of subfertility: Introducing the Cochrane Menstrual Disorders and Subfertility Group. (1999-01)
  • Cumulative probability of clinical pregnancy and live birth after a multiple cycle IVF package: A more realistic assessment of overall and age-specific success rates? (1999-02)
  • Pregnancy and birth rates after oocyte donation (1997)
  • Cumulative pregnancy rates and pregnancy outcome after in-vitro fertilization: > 5000 cycles at one centre (1995)
  • Pregnancies and births resulting from in vitro fertilization: French national registry, analysis of data 1986 to 1990 (1995)
  • The results of in vitro fertilization-embryo transfer in couples with unexplained infertility failing to conceive with superovulation and intrauterine insemination (1995)
  • Observations on 767 clinical pregnancies and 500 births after human in-vitro fertilization (1986)

What are the chances of us conceiving?

It is impossible to give an accurate prognosis. Some couples who seem to have everything going against them succeed whereas others who seem to have a good prognosis do not. Several specialists have suggested formulae to provide some assistance in answering this central question. We have devised the following formula:

Prognostic Fertility Index =  [50- Female Partner Age] x Male Factor x Tubal Factor

/ Years of Infertility

The Male factor is the number of millions of actively motile sperm per ml of semen

(Maximum = 5)

The Tubal Factor is assessed as follows:

5 – No known tubal disease.

4 – History of pelvic inflammatory disease both tubes patent.

3 – One tube patent and one blocked.

2 – One tube removed (e.g. For ectopic pregnancy) and the other tube patent.

1 – Both tubes blocked.

0 – Both tubes have been removed.

The number of years is calculated counting the current year as one. For examples:

trying for less than one year = 1.

trying for two years and six months = 3.

Our index does not include ovulation as ovulation induction treatment can usually overcome most ovulatory problems.

Examples of calculating the Prognostic Fertility Index are provided in Table 9.2.

Table 9.2 Examples of calculations of the Prognostic Fertility Index.

Age (Female) Male Factor (Q9.21) Tubal Factor Years of Infertility Prognostic Fertility Index
25 5 5 2 1/2 35

 

Related Medical Abstracts

  • Pregnancy is predictable: a large-scale prospective external validation of the prediction of spontaneous pregnancy in subfertile couples.(2007-01)
  • Evaluation of pregnancy rates after intrauterine insemination according to indication, age, and sperm parameters. (1998)
  • First and subsequent pregnancies after tubal microsurgery: Evaluation of the fertility index. (1997)
  • Prognosis for fertility analyzing different variables in men and women. (1996)
  • Score prognosis for the infertile couple based on historical factors and sperm analysis. (1994)
  • Fertility prognosis for infertile couples. (1993)
  • Age of the female partner is a prognostic factor in prolonged unexplained infertility: A multicentre study. (1989)
  • Duration of involuntary infertility and subsequent pregnancy. (1987-01)
  • Simple model and empirical method for the estimation of spontaneous pregnancies in couples consulting for infertility. (1987-02)

Infertility Support Groups

Members of a support group, provide each other with various types of help and information for a particular shared difficulty.

The support may take the form of providing relevant information,

  • relating personal experiences,
  • listening to others’ experiences,
  • providing sympathetic understanding and
  • establishing social networks.

A support group may also provide ancillary support, such as serving as a voice for the public or engaging in advocacy.

Support groups maintain interpersonal contact among their members in a variety of ways.

Support groups also maintain contact through printed information rich newsletters, telephone chains, internet forums, and mailing lists.

Support groups offer companionship and information for people coping with diseases or disabilities. Support groups may not be appropriate for everyone, and some find that a support group actually adds to their stress rather than relieving it.
There are some support groups specifically for people experiencing infertility, some of which have local groups and/or sub-groups specialising in particular issues.

Evaluation of the quality of Web sites is discussed in (internet information). You may find that several general women’s health sites may help you (internet information). The following are more specialised relevant Web sites:-

http://www.nor.com. Au/community/aisg/ Australian Infertility Support Group
http://www. Theafa.org The American Fertility Association, 305 Madison Avenue  Suite 449, New York, NY 10165
http://www.drwoolcott.com. Au
www.epigee.org/guide/infert.html
fertilethoughts.net Infertility Support Group Forums
http://www. Inciid.org/ The InterNational Council on Infertility Information Dissemination (INCIID ? pronounced “inside”) is a nonprofit organization that helps individuals and couples explore their family-building options.
www. Indiaparenting.com/fertility/index.htm
http://www. Infertility-info.com/ The IFC Resource Centre was set up as an independent facility to provide graphical information, books and CD-ROMs in the field of Reproductive Medicine.
http://www. Ivfconnections.com/
www.noah-health.org/en/pregnancy/fertility
Resolve RESOLVE: The National Infertility Association, established in 1974, is a non-profit organization with the only established, nationwide network of chapters mandated to promote reproductive health and to ensure equal access to all family building options for men and women experiencing infertility or other reproductive disorders.Headquarters: 8405 Greensboro Drive, Suite 800, McLean, VA 22102-5120
http://www. Acebabes.co.uk/
http://www. Advancedfertility.com
http://www.bica.net British Infertility Counselling Association, 69 Division Street, Sheffield, S1 4GE
http://www.bounty.com/Default. Aspx ISSUE (The National Fertility Association), 114 Litchfield Street, Walsall, WS1 1SZ

Are Infertility Treatments Improving?

New effective treatments arrive almost yearly. Some, such as letrozole (12A) are surprisingly simple to use and cost very little whereas others like ICSI (25) are extremely complex and expensive.

Until the 1960s treatment options were very limited. Anovulatory infertility (Q9.17) has only been treatable by drugs since the early 1960s; success rates from medication are high. If investigation showed evidence of blocked Fallopian tubes, surgery may prove successful for between ten and twenty percent. If there was evidence of severe male infertility, donor insemination was a possibility; until the last few years no more than 2% of men with severe infertility problems could be treated by other means. The arrival of IVF twenty years ago and the subsequent development of ICSI seven years ago have changed the picture completely now only 2% of couples with severe male factor infertility cannot be treated. Cryopreservation (freezing for storage and later thawing and utilisation) of embryos and ova, and embryo biopsy (28) are remarkable technical achievements that merit consideration. The latest development involves culturing the embryos for five days to the blastocyst stage. Implantation of blastocysts provides higher implantation rates than with embryo transfer at two days. It is hoped that eventually only one embryo will be transferred on the fifth day with a 70% chance of an ongoing pregnancy. Each development requires scientific analysis and raises difficult ethical questions.

Sadly, a successful outcome from infertility treatment cannot be guaranteed. Even with IVF there is only an average 20% success rate per cycle or about 50% with three treatment cycles. The emotional toll during treatment cycles cannot be adequately estimated and, when there is failure, devastation and at times despair are inevitable. Some couples will give up relatively early. For others parenthood seems their only purpose in life and they travel the world seeking success.

The latest data from the USA shows that

Overall, 42% of ART transfer procedures resulted in a pregnancy, and 35% resulted in a live-birth delivery (delivery of one or more live-born infants).2006-01In the 1990s typical pregnancy rates were in the order of 20%.

A couple I have known for many years were found to have male factor infertility. They chose to wait for a miracle rather than accept AID (23). Now aged fifty the lady poured her heart out to me. The miracle never happened. For this couple, developments including ICSI have come too late. I explained that even if they had elected to pursue donor insemination, success would not have been guaranteed but they are left with an empty feeling, as they never tried.

For those unfortunate couples who do not meet with success from treatment they will at least know that they tried although it was not to be. There may be an option for them to pursue adoption.

  • Assisted reproductive technology surveillance–United States, 2003. (2006-01)
  • Comparison of blastocyst transfer to day 3 transfer with assisted hatching in the older patient. (2002)
  • Blastocyst transfer for patients with multiple assisted reproduction treatment failures: Preliminary experience (2001)
  • The Human Rights Act (1998) and its impact on reproductive issues (2001).?
  • Blastocyst culture: toward single embryo transfers. (2000)
  • Assisted hatching increases the implantation and pregnancy rate of in vitro fertilization (IVF)-embryo transfer (ET), but not that of IVF-tubal ET in patients with repeated IVF failures (1997)
  • Salpingectomy improves the pregnancy rate in in-vitro fertilization patients with hydrosalpinx (1996)?
  • High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin (1994)
  • Five decades of progress in management of the infertile couple (1994)?
  • Assisted hatching in the treatment of poor prognosis in vitro fertilization candidates (1994)

Infertility Treatment and the risk of miscarriage

Miscarriage (Miscarriage) is estimated to occur in between 10 and 20% of pregnancies. A meta-analysis of assisted conception found a spontaneous miscarriage incidence of 22%. In a study in Ireland the outcome of pregnancies achieved by IVF were compared to those conceived spontaneously whilst awaiting treatment. There were 16.5% miscarriages in the IVF group compared to 5% in the spontaneous pregnancy group. The psychological effects of miscarriage following infertility treatment cannot be underestimated. There is evidence that 50% of male partners suffer significant disturbance.

  • Incidence of spontaneous abortion among pregnancies produced by assisted reproductive technology. (2004-01)
  • The lived experience of miscarriage after infertility. (2003-01)
  • Polycystic ovarian syndrome and the risk of spontaneous abortion following assisted reproductive technology treatment. (2001-01)
  • Pregnancy and miscarriage rates in 3978 donor insemination cycles: effect of age, parity and partner’s infertility status on pregnancy outcome. (2000-01)
  • Course and outcome of IVF pregnancies and spontaneous conceptions within an IVF setting (1995)
  • Incidence of fetal loss in infertility patients after detection of fetal heart activity with early transvaginal ultrasound (1993)

Infertility Treatment and the risk of ectopic pregnancy

Disorders of the Fallopian tube are more common in women with reduced fertility and there is an increased risk of ectopic pregnancy in those with a history of infertility. Even when embryos are transferred into the uterine cavity following IVF there is still a 4.5% chance of an ectopic compared to 1% in the general population.

  • Risk factors for ectopic pregnancy: a case-control study. (2006-01)
  • Ectopic Pregnancy Risk With Assisted Reproductive Technology Procedures (2006-02)
  • Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France. (2003-01)
  • Risk factors for ectopic pregnancy in assisted reproduction. (1999-01)

What is a heterotopic pregnancy and is it related to infertility treatment?

This is a multiple pregnancy with one embryo implanting in the uterine cavity and another is simultaneously ectopic. The natural incidence of heterotopic pregnancy is one in 30, 000. Infertility is associated with an increased risk of ectopic pregnancy and infertility treatment involving ovulation induction drugs increases the chance of multiple pregnancy. As a result of assisted conception, the incidence of heterotopic pregnancy has increased.

Ultrasound can assist early diagnosis of heterotopic pregnancy. In one study, two-thirds of the intrauterine pregnancies resulted in live births.

  • A comparison of heterotopic and intrauterine-only pregnancy outcomes after assisted reproductive technologies in the United States from 1999 to 2002. (2006-01)
  • Heterotopic pregnancy (2006-02)
  • Heterotopic pregnancy: two cases and a comparative review. (2006-03)
  • Ruptured heterotopic pregnancy with successful obstetrical outcome: a case report and review of the literature. (2005-01)
  • Heterotopic pregnancy after in vitro fertilization-embryo transfer. (2004-01)

Infertility and Multiple Pregnancy – The Risks

Infertility treatments involving ovulation induction are associated with an increased incidence of twins and higher order multiple pregnancy . The natural incidence of twins is one in eighty pregnancies and for triplets it is one in six thousand. Ovulation induction alone increases the incidence of twins four-fold. A study of twenty-four thousand IVF pregnancies found a 25-fold increase in the incidence of twins and a 350-fold increase in triplets.

 

Multiple pregnancy is regarded as ‘high-risk’ in obstetrics as all the potential complications of pregnancy occur more frequently. These include maternal problems such as anaemia, urinary tract infection, high blood pressure and bleeding. Miscarriage, premature delivery, poor placental function reducing the growth rate of the babies, perinatal mortality (stillbirths and babies dying in their first week) are all more frequent in twins. These problems are disproportionately more likely to occur with higher order pregnancies (Figure 11.2).

Figure 11.2

  • Preterm birth in twins after subfertility treatment: population based cohort study. (2005-01)
  • Perinatal outcomes of in vitro fertilization twins: a systematic review and meta-analyses. (2005-02)
  • The risk of mortality or cerebral palsy in twins: a collaborative population-based study. (2002-01)
  • Comparison of risk factors for cerebral palsy in twins and singletons. (2002-02)
  • Assisted reproductive technologies: Estimates of their contribution to multiple births and newborn hospital days in the United States (1996)
  • Perinatal outcome of twin pregnancies obtained after in vitro fertilization: Comparison with twin pregnancies obtained spontaneously or after ovarian stimulation (1996)
  • Perinatal outcome of triplet pregnancies following assisted reproduction (1994)
  • Triplets and quadruplets born in Victoria between 1982 and 1990: The impact of IVF and GIFT on rising birthrates (1993)
  • Outcome of twin, triplet, and quadruplet in vitro fertilization pregnancies: The Norfolk experience (1992)
  • Births in Israel resulting from in-vitro fertilization/embryo transfer, 1982-1989: National registry of the Israeli association for fertility research (1992)

Selective Termination of Pregnancy

Most pregnancies with three early gestation sacs (each sac usually contains one embryo) reduce spontaneously. In one study, there were 38 pregnancies with three gestation sacs between three and four weeks after IVF/embryo transfer. At delivery there were seven single babies, twelve twins and eighteen sets of triplets.

Selective termination is a procedure usually employed when one fetus is found to have a significant abnormality with the objective of allowing the pregnancy to continue with the expectation of delivery of the remaining healthy infant(s). Multifetal pregnancy reduction is the termination of one or more seemingly healthy fetuses with the objective of reducing the risks of higher order multiple pregnancies. Recent analysis of data from North East London showed that the neonatal death rate (babies dying in the first four weeks per 1000 live births) for a singleton pregnancy is 3.4, for twins 25.4 and for higher order it is 93.8. Multifetal pregnancy reduction has been shown to improve the perinatal outcome for pregnancy with four or more fetuses, although there is a 9% risk of losing the entire pregnancy.

The ethical issues associated with selective termination of a fetus with significant abnormality are identical to those pertaining when there is only one fetus. The ethical issues relating to multifetal pregnancy reduction are far more complex as it involves the sacrifice of one or more normal fetuses for the benefit of the remainder. Interestingly, a psychological assessment of surviving offspring and their parents in Holland found no adverse effects.

    • Information-sharing among couples considering multifetal pregnancy reduction. (2007-01)
  • Risks of miscarriage and early preterm birth in trichorionic triplet pregnancies with embryo reduction versus expectant management: new data and systematic review. (2006-01)
  • Lived experiences of Taiwanese women with multifetal pregnancies who receive fetal reduction. (2006-02)
  • Two hundred ninety consecutive cases of multifetal pregnancy reduction: comparison of the transabdominal versus the transvaginal approach. (2004-01)
  • Embryo reduction versus expectant management in triplet pregnancies. (2004-02)
  • Obstetric outcome and psychological follow-up of pregnancies after embryo reduction. (1999-01)
  • Multifetal reduction increases the risk of preterm delivery and fetal growth restriction in twins: A case-control study (1997)
  • Psychological reactions after multifetal pregnancy reduction: A 2-year follow-up study (1997)
  • The current status of multifetal pregnancy reduction (1996)
  • Pregnancy outcome after multifetal pregnancy reduction to twins compared with spontaneously conceived twins (1996)
  • Follow-up of pregnancies, infants, and families after multifetal pregnancy reduction (1994)
  • Improved results in multifetal pregnancy reduction: A report of 72 cases (1994)

How can the pregnancy risks following infertility treatment be reduced?

The greatest risks are associated with multiple pregnancy and this is largely dependent on the use of ovulation induction agents (4). A common reason for anovulation is PCOS (Q7.2) and ovulation induction agents have frequently been employed. The arrival of metformin as an effective treatment that reverses the underlying cause of PCOS may reduce the need for ovulation induction.

IVF is associated with increased incidence of multiple pregnancy. The success of IVF has given it an element of glamour. Ultimately it is a matter of patient choice but it is my own view that there is a place for fully exhausting lower-tech treatments before resorting to IVF. Fertility units are compared by their pregnancy rates and ‘take-home’ baby rates. There is an understandable temptation to put back as many embryos as possible to achieve positive results (Figure 11.1). Those of us who are involved in the care of the resultant pregnancies see the joys of successful outcomes but our views are chastened when we see things go wrong (see Q11.8). In the UK, the number of embryos that can be transferred into the uterus has been limited to three and there is current debate suggesting that we should further reduce to two. This is a move that many of us obstetricians would favour.

There is an advantage in pregnancies following infertility treatment being cared for by a team with a special interest in this area. Whilst I have no doubt that even greater vigilance is given in the care provided for pregnancies resulting from infertility treatment, there is evidence that successful outcomes occur slightly less frequently when compared with pregnancies achieved naturally. Doctors in general, and obstetricians in particular, are better placed than most to contemplate the miracles of nature. We do not intervene unless we believe that there is a definite advantage. When a pregnancy reaches term, there is no advantage for the baby to await events or to experience passage through the birth canal. An increasing proportion of women who have experienced infertility elect to be delivered by caesarean section.

There is a perceptible pressure to reduce obstetric intervention albeit mainly from those who have not experienced the occasional downside of natural childbirth. For those women who have experienced prolonged infertility and successful treatment, natural childbirth may seem less important than for others. There is an element of risk in every aspect of our lives and sadly there are times when even particularly precious pregnancies go wrong at the last moment. Usually, although not always, it is an unavoidable event of nature.

  • A two- versus three-embryo transfer: The oocyte donation model (2001)
  • Obstetric and perinatal outcome of pregnancies after intrauterine insemination. (1999)
  • Obstetric outcome in 232 ovum donation pregnancies. (1998)
  • Triplets and embryo transfer policy. (1997)
  • The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence (1994)

If we have infertility treatment, will our baby be healthy?

In spontaneous conception, the one follicle that has become dominant that cycle is fertilised by the sperm that has beaten all the others in a race. There have been millions of sperm released during the ejaculation. The concept of natural selection is dependent on the idea that the fittest survive. Infertility treatment, particularly IVF, ICSI and cryopreservation circumvent natural selection. There has been understandable concern that these infertility treatments may be associated with an increased risk of congenital abnormality. Reassuringly, however, results reported from around the world indicate that there is no major increase in the rate of babies being born with abnormality.

  • Follow-up of children born after ICSI. (2002)
  • Outcome and follow-up of children born after IVF-surrogacy (2001)
  • Pregnancy and child outcome after oocyte donation (2001)
  • Follow-up studies of children born after frozen sperm donation (2001)
  • Review: Parent-child relationships and child development in donor insemination families (2001)
  • Health of 227 children born after controlled ovarian stimulation for in vitro fertilization using the luteinizing hormone-releasing hormone antagonist cetrorelix (2001)
  • Obstetric outcome and follow-up of children born after in vitro fertilization (IVF) (2000)
  • Incidence of congenital malformations in children born after ICSI. (2000)information?
  • The psychological status at school age of children conceived by in-vitro fertilization. (1999)
  • Infants conceived using in-vitro fertilization do not over-utilize health care resources after the neonatal period. (1998)
  • Stigma, disclosure, and family functioning among parents of children conceived through donor insemination (1997)
  • Follow-up of a cohort of 422 children aged 6 to 13 years conceived by in vitro fertilization (1997)
  • Donor insemination: Child development and family functioning in lesbian mother families (1997)
  • Obstetric and perinatal outcome of pregnancies following intracytoplasmic sperm injection (1996)
  • Intelligence and behaviour in children born after in-vitro fertilization treatment (1996)
  • Growth and physical outcome of children conceived by in vitro fertilization (1996)
  • Assisted reproduction: A reassuring picture (1996)
  • The European study of assisted reproduction families: Family functioning and child development (1996)
  • Pregnancy outcome following exposure to gonadotrophin-releasing hormone analogue during early pregnancy: Comparisons in patients with normal or elevated luteinizing hormone (1995)
  • Outcome in children from cryopreserved embryos (1995)
  • Birth characteristics and perinatal outcome of babies conceived from cryopreserved embryos (1994)
  • A controlled study of the psycho-social development of children conceived following insemination with donor semen (1993)
  • Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer (1991)
  • Perinatal outcome and congenital malformations in in-vitro fertilization babies from the Bourn-Hallam group (1991)

What are the psychological effects of infertility treatment?

For those who have difficulty achieving parenthood, there is a feeling of unhappiness and reduced well-being. There are studies that confirm that infertile women in particular are particularly prone to psychological disturbance after long-term infertility. Anxiety, depression, a variety of health complaints and lack of self-esteem are more prevalent and may require support counselling and even supportive psychotherapy. Men do not escape psychological disturbance although this is more often repressed but subsequently leads to greater risk of psychosomatic illness (2).

  • Life after infertility treatment: A long-term investigation of marital and sexual function. (1998)information?
  • Psychological consequences of having triplets: A 4-year follow-up study (1997)information?
  • Facing the unacceptable: The emotional response to infertility (1997)information?
  • Long-term infertile couples: A study of their well-being (1993)information?
  • Quality of parenting in families created by the new reproductive technologies: A brief report of preliminary findings (1993)information?
  • The impact of infertility on psychological functioning (1992)information?
  • Successful parents of in vitro fertilization (IVF): The social repercussions (1992)

Infertility Treatment and Stress

  • The fertility problem inventory: Measuring perceived infertility-related stress. (1999)
  • Distress and reduced fertility: A follow-up study of first-pregnancy planners.(1999)
  • The experiences of couples who have had infertility treatment in the United Kingdom: Results of a survey performed in 1997. (1999)

Comparing Infertility Units

  • How do patients choose private in vitro fertilization treatment? A customer survey in a tertiary fertility center in the United Kingdom (2001)
  • Profiling assisted reproductive technology: Outcomes and quality of infertility management. (1998)

Internet Use by Infertile Couples

  • Use of the Internet by infertile couples.

How successful is infertility treatment?

  • Assisted reproductive technology in Europe, 2002. Results generated from European registers by ESHRE. (2006-01)
  • Intra-uterine insemination for unexplained subfertility.(2006-02)
  • A new era in ovulation induction.(2006-03)
  • Letrozole induction of ovulation in women with clomiphene citrate-resistant polycystic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle-stimulating hormone ratio.(2006-04)
  • Comparison of letrozole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation. (2006-05)
  • Clomiphene citrate–end of an era? A mini-review. (2005-01)
  • Systematic review of the treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination. (2004-01)
  • Case series of a single centre’s treatment of ovulatory infertility with clomiphene citrate and intrauterine insemination in 2002. (2004-02)
  • Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study. (2002)
  • Assisted reproductive technology in Europe, 1997. Results generated from European registers by ESHRE (2001)
  • Effective treatment of subfertility: Introducing the Cochrane Menstrual Disorders and Subfertility Group. (1999-01)
  • Cumulative probability of clinical pregnancy and live birth after a multiple cycle IVF package: A more realistic assessment of overall and age-specific success rates? (1999-02)
  • Pregnancy and birth rates after oocyte donation (1997)
  • Cumulative pregnancy rates and pregnancy outcome after in-vitro fertilization: > 5000 cycles at one centre (1995)
  • Pregnancies and births resulting from in vitro fertilization: French national registry, analysis of data 1986 to 1990 (1995)
  • The results of in vitro fertilization-embryo transfer in couples with unexplained infertility failing to conceive with superovulation and intrauterine insemination (1995)
  • Observations on 767 clinical pregnancies and 500 births after human in-vitro fertilization (1986)

Comparing Infertility Treatments

  • Cost-effective treatment of the infertile couple (1998)
  • Reliability of league tables of in vitro fertilisation clinics: Retrospective analysis of live birth rates. (1998)

Infertility Support Groups

Members of a support group, provide each other with various types of help for a particular shared difficulty. The support may take the form of providing relevant information, relating personal experiences, listening to others’ experiences, providing sympathetic understanding and establishing social networks. A support group may also provide ancillary support, such as serving as a voice for the public or engaging in advocacy. Support groups maintain interpersonal contact among their members in a variety of ways. Support groups also maintain contact through printed newsletters, telephone chains, internet forums, and mailing lists.

Support groups offer companionship and information for people coping with diseases or disabilities. Support groups may not be appropriate for everyone, and some find that a support group actually adds to their stress rather than relieving it.

http://www. Asrm.org/ The American Society for Reproductive Medicine is a voluntary, non-profit organization devoted to advancing knowledge and expertise in reproductive medicine, including infertility, menopause, contraception, and sexuality.
http://www.nor.com. Au/community/aisg/ The Australian Infertility Support Group
http://www. Theafa.org/ American Fertility Association
http://www.epigee.org/guide/infert.html Epigee – Natural Fertility
http://www.fertilethoughts.net/ Infertility Pregnancy Adoption Parenting Surrogacy
http://www. Inciid.org/ International Council on Infertility Information Dissemination
http://www. Indiaparenting.com India Fertility Issues, Preconception, Adoption, Baby Names
http://www. Infertility-info.com Tim Appleton – doctorates in cell biology, is an ordained Anglican Priest, and has been an independent Fertility Counsellor
http://www.noah-health.org Fertilty, Infertility, Surrogacy
http://www.resolve.org The National Infertility Association
http://www.fertilitynetwork.com Find Infertility specialists, fertility doctors, who perform advanced Infertility treatment, like IVF and ICSI,
http://www.hfea.gov.uk The Human Fertilisation and Embryology Authority is the UK’s independent regulator overseeing safe and appropriate practice in fertility treatment and embryo research.
http://www. Infertilitynetworkuk.com Infertility Network UK – Advice, Support and Understanding
http://www. Ivfglossary.org.uk Glossary of Infertility and IVF Terminology
http://www.dcnetwork.org/ A self-help network of over 1,000 families created with the help of donated eggs, sperm or embryos; couples and individuals seeking to found a family this way; and adults conceived using a donor.
http://www.ngdt.co.uk/ Clear and practical information mainly for those considering becoming an egg or sperm donor but also for health professionals and those requiring treatment with donor eggs or sperm.
http://www. Acebabes.co.uk/ ACeBabes was established as a UK charity in 1998 to support the growing number of people who were using assisted conception as a way to bring about their longed for family
  • Male Factor Infertility
  • Female Tubal Factor
  • Anovulation – Ovulation Induction
  • Unexplained Infertility

 

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