Infertility

Infertility is the inability to naturally conceive a child or the inability to carry a pregnancy to term. There are many reasons why a couple may not be able to conceive, or may not be able to conceive without medical assistance. (Note: although some aspects of this article may be generalizable, it deals primarily with infertility as pertains to human couples.)

Infertility causes

Definition

The International Council on Infertility Information Dissemination (INCIID) considers a couple to be infertile if¹:

• they have not conceived after 12 months of unprotected intercourse, or after 6 months if the woman is over 35 years of age. The reduced duration for women over 35 is because there is a rapid decline in fertility after this age and help should be sought sooner.
• there is incapability to carry a pregnancy to term.

Healthy couples in their mid-20s having regular sex have a one-in-four chance of getting pregnant in any given month. This is called "Fecundity".

Causes

This section deals with unintentional causes of sterility. For more information about surgical techniques for preventing procreation, see sterilization.

Primary vs. secondary

According to the American Society for Reproductive Medicine, infertility affects about 6.1 million people in the U.S., equivalent to ten percent of the reproductive age population. Female infertility accounts for one third of infertility cases, male infertility for another third, combined male and female infertility for another 15%, and the remainder of cases are "unexplained"².

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

"Secondary infertility" is difficulty conceiving after already having conceived and carried a normal pregnancy. Apart from various medical conditions (e.g. hormonal), this may come as a result of age and stress felt to provide a sibling for their first child. Technically, secondary infertility is not present if there has been a change of partners.

Female infertility

Factors relating to female infertility are:

• General factors
  • Diabetes mellitus, thyroid disorders, adrenal disease
  • Significant liver, kidney disease
  • Psychological factors
• Hypothalamic-pituitary factors:
  • Kallmann syndrome
  • Hypothalamic dysfunction
  • Hyperprolactinemia
  • Hypopituitarism
• Ovarian factors
  • Polycystic ovary syndrome
  • Anovulation
  • Diminished ovarian reserve
  • Luteal dysfunction
  • Premature menopause
  • Gonadal dysgenesis (Turner syndrome)
  • Ovarian neoplasm
• Tubal/peritoneal factors
  • Endometriosis
  • Pelvic adhesions
  • Pelvic inflammatory disease (PID, usually due to chlamydia)
  • Tubal occlusion
• Uterine factors
  • Uterine malformations
  • Uterine fibroids (leiomyoma)
  • Asherman's Syndrome
• Cervical factors
  • Cervical stenosis
  • Antisperm antibodies
  • Insufficent cervical mucus (for the travel and survival of sperm)
• Vaginal factors
  • Vaginismus
  • Vaginal obstruction
• Genetic factors
  • Various intersexed conditions, such as androgen insensitivity syndrome

Male infertility

Factors relating to male infertility include³:

• Pretesticular causes
  • Endocrine problems, i.e. diabetes mellitus, thyroid disorders
  • Hypothalamic disorders, i.e. Kallmann syndrome
  • Hyperprolactinemia
  • Hypopituitarism
  • Hypogonadism due to various causes
  • Psychological factors
  • Drugs, alcohol
• Testicular factors
  • Genetic defects on the Y chromosome
    • Y chromosome microdeletions
  • Abnormal set of chromosomes
    • Klinefelter syndrome
  • Neoplasm, e.g. seminoma
  • Idiopathic failure
  • Cryptorchidism
  • Varicocele
  • Trauma
  • Hydrocele
  • Mumps
• Posttesticular causes
  • Vas deferens obstruction
  • Infection, e.g. prostatitis
  • Retrograde ejaculation
  • Hypospadias
  • Impotence

Some causes of male infertility can be determined by analysis of the ejaculate, which contains the sperm. The analysis includes counting the number of sperm and measuring their motility under a microscope:

• Producing few sperm, oligospermia, or no sperm, azoospermia.
• A sample of sperm that is normal in number but shows poor motility, or asthenozoospermia.

In the majority of cases of male infertility and low sperm quality, no clear cause can be identified with current diagnostic methods. It has been speculated that random mutations of the Y chromosome may be an important factor. As the human Y chromosome is passed directly from father to son, it is not protected against accumulating copying errors, whereas other chromosomes are error corrected by recombining genetic information from mother and father. This may leave natural selection as the primary repair mechanism for the Y chromosome. Microdeletions in the Y chromosome have been found at a much higher rate in infertile men than in fertile controls and the correlation found may still go up as improved genetic testing techniques for the Y chromosome are developed. (Existing test kits for Y chromosome microdeletions with PCR markers cover only a tiny fraction of the chromosome's 23 million base pairs and therefore very likely still miss most mutations. The gold standard test for genetic mutation, namely complete DNA sequencing of a patient's Y chromosome, is still far too expensive for use in epidemiologic research or even clinical diagnostics.)

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

In about 15% of cases the infertility investigation will show no abnormalities. 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.

Treatment

• Fertility medication which stimulates the ovaries to "ripen" and release eggs (e.g. clomifene citrate, which stimulates ovulation)
• Surgery to restore patency of obstructed fallopian tubes (tuboplasty)
• Donor insemination which involves the woman being artificially inseminated with donor sperm.
• In vitro fertilization (IVF) in which eggs are removed from the woman, fertilized and then placed in the woman's uterus, bypassing the fallopian tubes. Variations on IVF include:
  • Use of donor eggs and/or sperm in IVF. This happens when a couple's eggs and/or sperm are unusable, or to avoid passing on a genetic disease.
  • Intracytoplasmic sperm injection (ICSI) in which a single sperm is injected directly into an egg; the fertilized egg is then placed in the woman's uterus as in IVF.
  • Zygote intrafallopian transfer (ZIFT) in which eggs are removed from the woman, fertilized and then placed in the woman's fallopian tubes rather than the uterus.
  • Gamete intrafallopian transfer (GIFT) in which eggs are removed from the woman, and placed in one of the fallopian tubes, along with the man's sperm. This allows fertilization to take place inside the woman's body.
• Other assisted reproductive technology (ART):
  • Assisted hatching
  • Fertility preservation
  • Freezing (cryopreservation) of sperm, eggs, & reproductive tissue
  • Frozen embryo transfer (FET)
• Alternative and complimetary treatments
  • Acupuncture Recent controlled trials published in Fertility and Sterility have shown acupuncture to increase the success rate of IVF by as much as 60%. Acupuncture was also reported to be effective in the treatment of female anovular infertility, World Health Organisation, Acupuncture: Review and Analysis of Reports on Controlled Trials (2002).
  • Diet and supplements
  • Healthy lifestyle

Costs

Not everyone in the U.S. has insurance coverage for fertility investigations and treatments, especially when a couple already has children. Many states are starting to mandate coverage.

2005 approximate treatment/diagnosis costs (United States, costs in US$):

• Initial workup: hysteroscopy, hysterosalpingogram, blood tests ~$2,000
• Artificial insemination ~ $500- 900 per. trial
• Sonohysterogram (SHG) ~ $600 - 1,000
• Clomiphene citrate cycle ~ $ 200 - 500
• IVF cycle ~ $10,000 -14,000
• Use of a surrogate mother to carry the child - dependent on arrangements

Another way to look at costs is to determine the cost of establishing a pregnancy. Thus if a clomiphene treatment has a chance to establish a pregnancy in 8% of cycles and costs $500, it will cost ~ $6,000 to establish a pregnancy, compared to an IVF cycle (cycle fecundity 40%) with a corresponding cost of ($12,000/40%) $30,000.

In the UK all patients have the right to preliminary testing, provided free of charge by the National Health Service. However, treatment is not widely available on the NHS and there can be long waiting lists. Most patients therefore seek help from private clinics⁴.

Ethics

There are many ethical issues associated with infertility and its treatment.

• High-cost treatments are out of financial reach for some couples.
• Debate over whether health insurance companies should be forced to cover infertility treatment.
• The legal status of embryos fertilized in vitro and not transferred in vivo.
• Pro-life opposition to the destruction of embryos not transferred in vivo.
• IVF and other fertility treatments have resulted in an increase in multiple births, provoking ethical analysis because of the link between multiple pregnancies, premature birth, and a host of health problems.
• Religious leaders' instructions on fertility treatments.
• Infertility caused by DNA defects on the Y chromosome is passed on from father to son. If natural selection is the primary error correction mechanism that prevents random mutations on the Y chromosome, then fertility treatments for men with abnormal sperm (in particular ICSI) only defer the underlying problem to the next male generation.

Psychological impact

Infertility may have profound psychological effects. Partners may become more anxious to conceive, ironically increasing sexual dysfunction. Marital discord often develops in infertile couples, especially when they are under pressure to make medical decisions. Women trying to conceive often have clinical depression rates similar to women who have heart disease or cancer⁵.

Social impact

In many cultures, inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment.

There are also legal ramifications as well. Infertility has begun to gain more exposure to legal domains. An estimated 4 million workers in the U.S. used the Family and Medical Leave Act (FMLA) in 2004 to care for a child, parent or spouse, or because of their own personal illness. Many treatments for infertility, including diagnostic tests, surgery and therapy for depression, can qualify one for FMLA leave.

External links

• International Council on Infertility Information Dissemination (INCIID)
• RESOLVE: U.S. infertility nonprofit since 1974
• "'Infertility time bomb' warning" at BBC News
• Infertility: Causes, Treatment Options and More (womenshealthchannel)
• CBC Digital Archives - Fighting Female Infertility
• How To Get Pregnant-The classic guide to overcoming infertility by Dr. Sherman Silber

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