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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 - Click on the paper title:-
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:
Source: Management of the Infertile Woman by Helen A. Carcio and The Fertility Sourcebook by M. Sara Rosenthal
Related Medical Abstracts - Click on the paper title:-
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).
The three most common causes of infertility are: 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 - Click on the paper title:-
What are the objectives of infertility investigations? The objectives in requesting 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.
If a couple have had a pregnancy where the baby or foetus had
a neural tube defect (NTD- spina-bifida type problem) they have an
increased risk of a similar problem recurring in the order of
one in a hundred. Controlled trials (placebo
& controlled trials) have demonstrated that folic acid
supplements (4 or 5mg daily) reduces this risk by 75% and it is
believed that benefit is likely even if you have never
experienced such a problem. The folic acid is not specifically
recommended because of infertility but would be advised for any
woman planning to conceive. During 2000 and 2002, all of the
women having pregnancies with birth defects and women whose
pregnancies were without any birth defects were interviewed.
Nine NTDs were recorded from 25,444 pregnancies (NTD birth
prevalence = 0.35/1,000 pregnancies) in the intervention
group and 48 NTDs among 26,599 pregnancies (NTD birth
prevalence = 1.80/1,000 pregnancies) in the control group.
The protective rate was 80.4%. The study suggests that
multivitamin supplement containing folic acid taken from a
time point of 2 months before conception and continuing
until completion of the second month after conception and
taken more than five times per week can significantly reduce
the risks of NTDs.0801
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 requesting 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 -
Q10.25). Related Medical Abstracts - Click on the paper title:-
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. Results of 6139 artificial insemination cycles with donor spermatozoa. Related Medical Abstracts - Click on the paper title:-
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 - Click on the paper title:-
I have fibroids. Could they affect my
fertility?
Fibroids (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 - Click on the paper title:-
Fibroids
- Treatment
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Figure 9.2 Investigation of Infertility
Related Medical Abstracts - Click on the paper title:-
- Optimal use of infertility diagnostic tests and treatments. (2000)
- Practice patterns among reproductive endocrinologists: Further aspects of the infertility evaluation (1998)
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 (Q10.23) or IVF seem more appropriate.
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.
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). 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.
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).
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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.
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.
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 - Q10.25), 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 (Q10.12A) 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.
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% (Figure 10.5)
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.
- 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)
Recommended Book:
Fertility and Infertility for Dummies (For Dummies)
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)
Recommended Book:
This page was last updated 12th December 2006
Making Babies the Hard Way: Living with Infertility and Treatment
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.
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).
