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Infertility

Infertility

Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult organism, except notably among certain eusocial species (mostly haplodiploid insects).

In humans, infertility may describe a woman who is unable to conceive as well as being unable to carry a pregnancy to full term. There are many biological and other causes of infertility, including some that medical intervention can treat. Estimates from 1997 suggest that worldwide "between three and seven per cent of all [heterosexual] couples or women have an unresolved problem of infertility. Many more couples, however, experience involuntary childlessness for at least one year: estimates range from 12% to 28%." 20-30% of infertility cases are due to male infertility, 20-35% are due to female infertility, and 25-40% are due to combined problems in both parts. In 10-20% of cases, no cause is found. The most common cause of female infertility is ovulatory problems which generally manifest themselves by sparse or absent menstrual periods. Male infertility is most commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.

Women who are fertile experience a natural period of fertility before and during ovulation, and they are naturally infertile during the rest of the menstrual cycle. Fertility awareness methods are used to discern when these changes occur by tracking changes in cervical mucus or basal body temperature.

 

Causes

Sexually transmitted diseases

Infections with the following sexually transmitted pathogens have a negative effect on fertility: Chlamydia trachomatis and Neisseria gonorrhoeae. There is a consistent association of Mycoplasma genitalium infection and female reproductive tract syndromes. M. genitalium infection is associated with increased risk of infertility.

Genetic

Main article: Genetics of infertility

A Robertsonian translocation in either partner may cause recurrent spontaneous abortions or complete infertility.

Other causes

Factors that can cause male as well as female infertility are:

DNA damage

DNA damage reduces fertility in female ovocytes, as caused by smoking, other xenobiotic DNA damaging agents (such as radiation or chemotherapy) or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine

DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage, smoking, other xenobiotic DNA damaging agents (such as drugs or chemotherapy) or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature

General factors

Diabetes mellitus, thyroid disorders, undiagnosed and untreated coeliac disease, adrenal disease

Hypothalamic-pituitary factors

Hyperprolactinemia

Hypopituitarism

The presence of anti-thyroid antibodies is associated with an increased risk of unexplained subfertility with an odds ratio of 1.5 and 95% confidence interval of 1.1–2.0.

Environmental factors

Toxins such as glues, volatile organic solvents or silicones, physical agents, chemical dusts, and pesticides. Tobacco smokers are 60% more likely to be infertile than non-smokers.

German scientists have reported that a virus called Adeno-associated virus might have a role in male infertility, though it is otherwise not harmful. Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring (fallopian tube obstruction).

Females

Further information: Female infertility

The following causes of infertility may only be found in females. For a woman to conceive, certain things have to happen: vaginal intercourse must take place around the time when an egg is released from her ovary; the system that produces eggs has to be working at optimum levels; and her hormones must be balanced.

For women, problems with fertilisation arise mainly from either structural problems in the Fallopian tube or uterus or problems releasing eggs. Infertility may be caused by blockage of the Fallopian tube due to malformations, infections such as chlamydia and/or scar tissue. For example, endometriosis can cause infertility with the growth of endometrial tissue in the Fallopian tubes and/or around the ovaries. Endometriosis is usually more common in women in their mid-twenties and older, especially when postponed childbirth has taken place.

Another major cause of infertility in women may be the inability to ovulate. Malformation of the eggs themselves may complicate conception. For example, polycystic ovarian syndrome is when the eggs only partially developed within the ovary and there is an excess of male hormones. Some women are infertile because their ovaries do not mature and release eggs. In this case synthetic FSH by injection or Clomid (Clomiphene citrate) via a pill can be given to stimulate follicles to mature in the ovaries.

Other factors that can affect a woman's chances of conceiving include being overweight or underweight, or her age as female fertility declines after the age of 30.

Sometimes it can be a combination of factors, and sometimes a clear cause is never established.

Common causes of infertility of females include:

ovulation problems (e.g. polycystic ovarian syndrome, PCOS, the leading reason why women present to fertility clinics due to anovulatory infertility.)

tubal blockage

pelvic inflammatory disease caused by infections like tuberculosis

age-related factors

uterine problems

previous tubal ligation

endometriosis

advanced maternal age

Males

Further information: Male infertility

The main cause of male infertility is low semen quality. In men who have the necessary reproductive organs to procreate, infertility can be caused by low sperm count due to endocrine problems, drugs, radiation, or infection. There may be testicular malformations, hormone imbalance, or blockage of the man's duct system. Although many of these can be treated through surgery or hormonal substitutions, some may be indefinite. Infertility associated with viable, but immotile sperm may be caused by primary ciliary dyskinesia. The sperm must provide the zygote with DNA, Centrioles, and Activation Factor for the embryo to develop. A defect in any of these sperm structures may result in infertility that will not be detected by semen analysis.

Combined infertility

In some cases, both the man and woman may be infertile or sub-fertile, and the couple's infertility arises from the combination of these conditions. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile but the couple cannot conceive together without assistance.

Unexplained infertility

Main article: Unexplained infertility

In the US, up to 20% of infertile couples have unexplained infertility. In these cases abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. However, a growing body of evidence suggests that epigenetic modifications in sperm may be partially responsible.

 

Diagnosis

If both partners are young and healthy and have been trying to conceive for one year without success, a visit to a physician or women's health nurse practitioner (WHNP) could help to highlight potential medical problems earlier rather than later. The doctor or WHNP may also be able to suggest lifestyle changes to increase the chances of conceiving.

Women over the age of 35 should see their physician or WHNP after six months as fertility tests can take some time to complete, and age may affect the treatment options that are open in that case.

A doctor or WHNP takes a medical history and gives a physical examination. They can also carry out some basic tests on both partners to see if there is an identifiable reason for not having achieved a pregnancy. If necessary, they refer patients to a fertility clinic or local hospital for more specialized tests. The results of these tests help determine the best fertility treatment.

 

Treatment

Treatment depends on the cause of infertility, but may include counselling, fertility treatments, which include in vitro fertilization. According to ESHRE recommendations, couples with an estimated live birth rate of 40% or higher per year are encouraged to continue aiming for a spontaneous pregnancy. Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods. Drugs used for both women and men include clomiphene citrate, human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) analogues, aromatase inhibitors, and metformin.

Medical treatments

Medical treatment of infertility generally involves the use of fertility medication, medical device, surgery, or a combination of the following. If the sperm are of good quality and the mechanics of the woman's reproductive structures are good (patent fallopian tubes, no adhesions or scarring), a course of ovarian stimulating medication maybe used. The physician or WHNP may also suggest using a conception cap cervical cap, which the patient uses at home by placing the sperm inside the cap and putting the conception device on the cervix, or intrauterine insemination (IUI), in which the doctor or WHNP introduces sperm into the uterus during ovulation, via a catheter. In these methods, fertilization occurs inside the body.

If conservative medical treatments fail to achieve a full term pregnancy, the physician or WHNP may suggest the patient undergo in vitro fertilization (IVF). IVF and related techniques (ICSI, ZIFT, GIFT) are called assisted reproductive technology (ART) techniques.

ART techniques generally start with stimulating the ovaries to increase egg production. After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman's reproductive tract, in a procedure called embryo transfer.

Other medical techniques are e.g. tuboplasty, assisted hatching, and Preimplantation genetic diagnosis.

Tourism

Main article: Fertility tourism

Fertility tourism is the practice of traveling to another country for fertility treatments. It may be regarded as a form of medical tourism. The main reasons for fertility tourism are legal regulation of the sought procedure in the home country, or lower price. In-vitro fertilization and donor insemination are major procedures involved.

Epidemiology

Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the failure to conceive.

Infertility rates have increased by 4% since the 1980s, mostly from problems with fecundity due to an increase in age.

Fertility problems affect one in seven couples in the UK. Most couples (about 84%) who have regular sexual intercourse (that is, every two to three days) and who do not use contraception get pregnant within a year. About 92 out of 100 couples who are trying to get pregnant do so within two years.

Women become less fertile as they get older. For women aged 35, about 94% who have regular unprotected sexual intercourse get pregnant after three years of trying. For women aged 38, however, only about 77%. The effect of age upon men's fertility is less clear.

In people going forward for IVF in the UK, roughly half of fertility problems with a diagnosed cause are due to problems with the man, and about half due to problems with the woman. However, about one in five cases of infertility has no clear diagnosed cause.

In Britain, male factor infertility accounts for 25% of infertile couples, while 25% remain unexplained. 50% are female causes with 25% being due to anovulation and 25% tubal problems/other.

In Sweden, approximately 10% of couples wanting children are infertile. In approximately one third of these cases the man is the factor, in one third the woman is the factor, and in the remaining third the infertility is a product of factors on both parts.