The Outcome of Infertility Treatment- Chapter 11:

Q 11. 1 How successful is infertility treatment?

The ultimate objective of infertility treatment is the delivery of a healthy child into a loving and supportive family environment. Infertility affects 15% of couples and it has been estimated that half of those couples who attend infertility clinics will be successful but equally about half do not achieve the baby they seek. New treatments for infertility enhance our chance of success but couples are delaying their pregnancies (Q9.5) and this reduces fertility. Furthermore, as the reputation of infertility treatment improves, couples with a poor prognosis continue to seek treatment whereas a few years ago they would have given up earlier.

References:

Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study. (2002) 3544

Assisted reproductive technology in Europe, 1997. Results generated from European registers by ESHRE (2001) 11-01-3412

Effective treatment of subfertility: Introducing the Cochrane Menstrual Disorders and Subfertility Group. (chapter 1999) 11-01-2731

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) 11-01-2552

Success rate with repeated cycles of in vitro fertilization-embryo transfer (1998) 11-01-2199

Pregnancy and birth rates after oocyte donation (1997) 11-01-1695

Cumulative pregnancy rates and pregnancy outcome after in-vitro fertilization: > 5000 cycles at one centre (1995) 11-01-1443

Pregnancies and births resulting from in vitro fertilization: French national registry, analysis of data 1986 to 1990 (1995) 11-01-1442

The results of in vitro fertilization-embryo transfer in couples with unexplained infertility failing to conceive with superovulation and intrauterine insemination (1995) 11-01-715

Infertility-epidemiology and referral practice (1991) 11-01-2089

Observations on 767 clinical pregnancies and 500 births after human in-vitro fertilization (1986) 11-01-1429

A decade’s experience with an individualized clomiphene treatment regimen including its effect on the postcoital test (1982) 11-01-684

Q 11. 1 How successful is infertility treatment?
Q 11. 2 How can we compare infertility treatments?
Q 11. 3 How can we compare outcomes between different fertility units?
Q 11. 4 Are treatments for infertility improving?
Q 11. 5 Is there an increased chance of miscarriage following infertility treatment?
Q 11. 6 Is there an increased chance of ectopic pregnancy following infertility treatment?
Q 11. 7 What is a heterotopic pregnancy?
Q 11. 8 What problems can occur with multiple pregnancy?
Q 11. 9 What is selective termination of pregnancy?
Q 11. 10 How can the pregnancy risks following infertility treatment be reduced?
Q 11. 11 We have had infertility treatment which has been successful. How will our pregnancy be cared for?
Q 11. 12 If we have infertility treatment, will our baby be healthy?
Q 11. 13 What are the psychological effects of infertility?
Q 11. 14 Where can I obtain more information?
Q 11. 15 Could I have some useful Web sites?
Women’s Health – Home Page

Q 11. 2 How can we compare 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 – Q10.25), for example, has resulted in a fall in donor insemination treatment cycles.

References:

Cost-effective treatment of the infertile couple (1998) 11-02-2496

Reliability of league tables of in vitro fertilisation clinics: Retrospective analysis of live birth rates. (1998) 11-02-2327

Q 11. 3 How can we compare outcomes between different fertility units?

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.

References:

How do patients choose private in vitro fertilization treatment? A customer survey in a tertiary fertility center in the United Kingdom (2001) 11-03-3359

Profiling assisted reproductive technology: Outcomes and quality of infertility management. (1998) 11-03-2220

Q 11. 4 Are treatments for infertility improving?

New effective treatments arrive almost yearly. Some, such as metformin for patients with PCOS (Q7.14) are surprisingly simple to use and cost very little whereas others like ICSI (Q10.25) 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 (Q10.28) 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.

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 (Q10.23). 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.

Pregnancy following successful infertility treatment:

All parents-to-be have natural anxieties about the outcome of pregnancy. We all ask: –

• Will a miscarriage occur?

• How many babies will there be?

• Will there be any complications during the pregnancy?

• Will our baby be healthy?

• Will we be able to cope with a child and be good parents?

For couples who have experienced delays in achieving pregnancy these anxieties are understandably greater.

References:

Comparison of blastocyst transfer to day 3 transfer with assisted hatching in the older patient. (2002) 3580

The Human Rights Act (1998) and its impact on reproductive issues. 3304

Blastocyst culture: toward single embryo transfers. (2000) 3221

Blastocyst transfer for patients with multiple assisted reproduction treatment failures: Preliminary experience (2001) 11-04-3372

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) 11-04-1797

Salpingectomy improves the pregnancy rate in in-vitro fertilization patients with hydrosalpinx (1996) 11-04-1249

High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin (1994) 11-04-406

Five decades of progress in management of the infertile couple (1994) 11-04-402

Assisted hatching in the treatment of poor prognosis in vitro fertilization candidates (1994) 11-04-370

Q 11. 5 Is there an increased chance of miscarriage following infertility treatment?

Miscarriage (Q12.1) 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.

References:

Course and outcome of IVF pregnancies and spontaneous conceptions within an IVF setting (1995) 11-05-1422

Incidence of fetal loss in infertility patients after detection of fetal heart activity with early transvaginal ultrasound (1993) 11-05-1413

Q 11. 6 Is there an increased chance of ectopic pregnancy following infertility treatment?

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 0.5% in the general population.

Q 11. 7 What is a heterotopic pregnancy?

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.

References:

Heterotopic pregnancy after ovulation induction and assisted reproductive technologies: A literature review from 1971 to 1993 (1996) 11-07-1394

Q 11. 8 What problems can occur with multiple pregnancy?

Infertility treatments involving ovulation induction are associated with an increased incidence of twins and higher order multiple pregnancy (Q10.4; Figure 11.1). 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).

References:

Assisted reproductive technologies: Estimates of their contribution to multiple births and newborn hospital days in the United States (1996) 11-08-1176

Perinatal outcome of twin pregnancies obtained after in vitro fertilization: Comparison with twin pregnancies obtained spontaneously or after ovarian stimulation (1996) 11-08-1395

Perinatal outcome of triplet pregnancies following assisted reproduction (1994) 11-08-1444

Triplets and quadruplets born in Victoria between 1982 and 1990: The impact of IVF and GIFT on rising birthrates (1993) 11-08-1437

Outcome of twin, triplet, and quadruplet in vitro fertilization pregnancies: The Norfolk experience (1992) 11-08-1052

Births in Israel resulting from in-vitro fertilization/embryo transfer, 1982-1989: National registry of the Israeli association for fertility research (1992) 11-08-1450

Q 11. 9 What is 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.

References:

Obstetric outcome and psychological follow-up of pregnancies after embryo reduction. (1999 ) 11-09-2764

Multifetal reduction increases the risk of preterm delivery and fetal growth restriction in twins: A case-control study (1997) 11-09-1616

Psychological reactions after multifetal pregnancy reduction: A 2-year follow-up study (1997) 11-09-1876

The current status of multifetal pregnancy reduction (1996) 11-09-1398

Pregnancy outcome after multifetal pregnancy reduction to twins compared with spontaneously conceived twins (1996) 11-09-1513

Follow-up of pregnancies, infants, and families after multifetal pregnancy reduction (1994) 11-09-1417

Improved results in multifetal pregnancy reduction: A report of 72 cases (1994) 11-09-358

Q 11.10 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 (Q10.4). 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.

References:

A two- versus three-embryo transfer: The oocyte donation model (2001) 11-10-3248.htm

Obstetric and perinatal outcome of pregnancies after intrauterine insemination. (1999) 11-10-2762.htm

Obstetric outcome in 232 ovum donation pregnancies. (1998) 11-10-2537.htm

Triplets and embryo transfer policy. (1997) 11-10-2912.htm

The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence (1994) 11-10-1129

Q 11. 11 We have had infertility treatment which has been successful. How will our pregnancy be cared for?

Every pregnancy and baby is precious to the professionals privileged to care for you during pregnancy and childbirth and we recognise that a pregnancy following successful infertility treatment is particularly precious. Obstetricians must walk a tight-rope between allowing nature to take its course and intervention when this is to the benefit of mother or baby. When infertility treatment has been necessary, increased vigilance and intervention are necessary. We believe that there is a self-evident advantage when the team involved in your infertility treatment can continue care through the pregnancy.

The decision to undertake a Caesarean section is usually reached by taking into account a combination of factors. A history of infertility, particularly when pregnancy has been achieved after many years and with high-tech treatment, is considered to be one factor in favour of operative delivery. Maternal age tends to be higher and there may be concern about the function of the placenta. Multiple pregnancy may be an additional reason for opting for Caesarean section. The Caesarean section rate for women conceiving with IVF in the Irish study (Q11.5) was 55.7% compared to 10.9% in the group conceiving spontaneously whilst awaiting IVF.

The question of whether obstetricians undertake too many or too few Caesarean sections can never be resolved as it is impossible to define the ideal operative delivery rate. Ultimately it is for the individual informed couple, together with their obstetrician, to decide on their preferred type of delivery. Safety and patient satisfaction are the quality measures that matter. There has been a notable increase in the number of women electing to be delivered by Caesarean section.

Bibliography:

Perinatal outcome and developmental studies on children born after IVF.. 11-11-3529

Q 11. 12 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.

References:

Follow-up of children born after ICSI. 11-12-3528

Outcome and follow-up of children born after IVF-surrogacy (2001) 11-12-3300

Pregnancy and child outcome after oocyte donation (2001) 11-12-3301

Follow-up studies of children born after frozen sperm donation (2001) 11-12-3302

Review: Parent-child relationships and child development in donor insemination families (2001) 11-12-3303

Health of 227 children born after controlled ovarian stimulation for in vitro fertilization using the luteinizing hormone-releasing hormone antagonist cetrorelix (2001) 11-12-3243

Obstetric outcome and follow-up of children born after in vitro fertilization (IVF) (2000) 11-12-3032

Incidence of congenital malformations in children born after ICSI. (2000) 11-12-3062

The psychological status at school age of children conceived by in-vitro fertilization. (1999) 11-12- 2763

Infants conceived using in-vitro fertilization do not over-utilize health care resources after the neonatal period. (1998) 11-12-2325

Stigma, disclosure, and family functioning among parents of children conceived through donor insemination (1997) 11-12-1803

Follow-up of a cohort of 422 children aged 6 to 13 years conceived by in vitro fertilization (1997) 11-12-2022

Donor insemination: Child development and family functioning in lesbian mother families (1997) 11-12-1858

Obstetric and perinatal outcome of pregnancies following intracytoplasmic sperm injection (1996) 11-12-1349

Intelligence and behaviour in children born after in-vitro fertilization treatment (1996) 11-12-1461

Growth and physical outcome of children conceived by in vitro fertilization (1996) 11-12-1475

Assisted reproduction: A reassuring picture (1996) 11-12-1483

The European study of assisted reproduction families: Family functioning and child development (1996) 11-12-1598

Pregnancy outcome following exposure to gonadotrophin-releasing hormone analogue during early pregnancy: Comparisons in patients with normal or elevated luteinizing hormone (1995) 11-12-1170

Outcome in children from cryopreserved embryos (1995) 11-12-1476

Birth characteristics and perinatal outcome of babies conceived from cryopreserved embryos (1994) 11-12-1451

A controlled study of the psycho-social development of children conceived following insemination with donor semen (1993) 11-12-1482

Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer (1991) 11-12-688

Perinatal outcome and congenital malformations in in-vitro fertilization babies from the Bourn-Hallam group (1991) 11-12-1448

Pregnancy complications and short-term follow-up of infants born after in vitro fertilization and embryo transfer (IVF/ET) (1991) 11-12-1449

Pregnancy outcome, health of children, and family adjustment after donor insemination (1990) 11-12-1447

Q 11. 13 What are the psychological effects of infertility?

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 (Q23.2).

References:

Life after infertility treatment: A long-term investigation of marital and sexual function. (1998) 11-13-2488

Psychological consequences of having triplets: A 4-year follow-up study (1997) 11-13-1720

Facing the unacceptable: The emotional response to infertility (1997) 11-13-2072

Long-term infertile couples: A study of their well-being (1993) 11-13-1425

Quality of parenting in families created by the new reproductive technologies: A brief report of preliminary findings (1993) 11-13-1477

The impact of infertility on psychological functioning (1992) 11-13-1055

Successful parents of in vitro fertilization (IVF): The social repercussions (1992) 11-13-1414

Q 11. 14 Where can I obtain more information?

Multiple Births Foundation

Queen Charlotte’s & Chelsea Hospital.

Q 11. 15 Could I have some useful Web sites?

Evaluation of the quality of Web sites is discussed in Q4.27. You may find that several general women’s health sites may help you (Q4.28). The following are more specialised Web sites on topics found in this chapter:-

This page was last updated on 19-Jun-2002

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Q 11. 1 How successful is infertility treatment?

References:

Q 11. 2 How can we compare infertility treatments?

References:

Q 11. 3 How can we compare outcomes between different fertility units?

References:

Q 11. 4 Are treatments for infertility improving?

References:

Q 11. 5 Is there an increased chance of miscarriage following infertility treatment?

References:

Q 11. 6 Is there an increased chance of ectopic pregnancy following infertility treatment?

Q 11. 7 What is a heterotopic pregnancy?

References:

Q 11. 8 What problems can occur with multiple pregnancy?

References:

Q 11. 9 What is selective termination of pregnancy?

References:

Q 11.10 How can the pregnancy risks following infertility treatment be reduced?

References:

Q 11. 11 We have had infertility treatment which has been successful. How will our pregnancy be cared for?

Bibliography:

Q 11. 12 If we have infertility treatment, will our baby be healthy?

References:

Q 11. 13 What are the psychological effects of infertility?

References:

Q 11. 14 Where can I obtain more information?

Q 11. 15 Could I have some useful Web sites?

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