Human (Female) Reproduction - Infertility

Infertility

primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term. There are many biological causes of infertility, some which may be bypassed with medical intervention. 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.

Definition

There are strict definitions of infertility used by many doctors. However, there are also similar terms, e.g. subfertility for a more benign condition and fecundity for the natural improbability to conceive. Infertility in a couple can be due to either the woman or the man, not necessarily both.

Infertility

Reproductive endocrinologists, the doctors specializing in infertility, consider a couple to be infertile if:

  1. the couple has not conceived after 12 months of contraceptive-free intercourse if the female is under the age of 34.                                                                                                                                       
  2. the couple has not conceived after 6 months of contraceptive-free intercourse if the female is over the age of 35 (declining egg quality of females over the age of 35 account for the age-based discrepancy as when to seek medical intervention).                                                                                                                                                                                                                                            
  3. the female is incapable of carrying a pregnancy to term.

Subfertility

A couple that has tried unsuccessfully to have a child for a year or more is said to be subfertile meaning less fertile than a typical couple. The couple`s fecundability rate is approximately 3-5%. Many of its causes are the same as those of infertility. Such causes could be endometriosis, or polycystic ovarian syndrome.

Primary vs. secondary infertility

Couples with primary infertility have never been able to conceive, while, on the other hand, secondary infertility is difficulty conceiving after already having conceived (and either carried the pregnancy to term, or had a miscarriage). Technically, secondary infertility is not present if there has been a change of partners.

Prevalence

  1. Generally, worldwide it is estimated that one in seven couples have problems conceiving, with the incidence similar in most countries independent of the level of the country`s development.                          
  2. Fertility problems affect one in seven couples in the UK. Most couples (about 84 out of every 100) who have regular sexual intercourse (that is, every 2 to 3 days) and who do not use contraception will get pregnant within a year. About 92 out of 100 couples who are trying to get pregnant do so within 2 years.                                                                                                                                                   
  3. Women become less fertile as they get older. For women aged 35, about 94 out of every 100 who have regular unprotected sexual intercourse will get pregnant after 3 years of trying. For women aged 38, however, only 77 out of every 100 will do so. The effect of age upon men s fertility is less clear.                                                                                                                                                                
  4. 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 have no clear diagnosed cause                                                                                                                                                                                                                                      
  5. 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                      
  6. In Sweden, approximately 10% of couples 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.

Causes

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

  1. Ovulation problems
  2. tubal blockage
  3. male associated infertility
  4. age-related factors
  5. uterine problems
  6. previous tubal ligation
  7. previous vasectomy
  8. unexplained infertility
  9. Tuberculosis (TB)
  10. Male Hypospadias

Virus/Mutation

German scientists have reported that a virus called Adeno-associated virus might have a role in male infertility, though it is otherwise not harmful. Mutation that alters human DNA adversely can cause infertility, the human body thus preventing the tainted DNA from being passed on. This could explain why some radiation victims from Chernobyl incident could not produce children.

Causes in either sex

For a woman to conceive, certain things have to happen: intercourse must take place around the time when an egg is released from her ovary; the systems that produce eggs and sperm have to be working at optimum levels; and her hormones must be balanced. There are several possible reasons why it may not be happening naturally. In one-third of cases, it can be because of male problems such as low sperm count. 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. Problems affecting women include endometriosis or damage to the fallopian tubes (which may have been caused by infections such as chlamydia). Other factors that can affect a woman`s chances of conceiving include being over- or underweight for her age female fertility declines sharply after the age of 35. Sometimes it can be a combination of factors, and sometimes a clear cause is never established. Factors that can cause male as well as female infertility are:

  1. Genetic Factors
    1. A Robertsonian translocation in either partner may cause recurrent spontaneous abortions or complete infertility.
  2. General factors
    1. Diabetes mellitus, thyroid disorders, adrenal disease
  3. Hypothalamic-pituitary factors
    1. Kallmann syndrome
    2. Hyperprolactinemia
    3. Hypopituitarism
  4. Environmental Factors
    • Toxins such as glues, volatile organic solvents or silicones, physical agents, chemical dusts, and pesticides.

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.

Assessment

If both partners are young and healthy, and have been trying for a baby for 12 months to two years without success, a visit to the family doctor could help to highlight potential medical problems earlier rather than later. The doctor may also be able to suggest lifestyle changes to increase the chances of conceiving. Women over the age of 35 should see their family doctor 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 family doctor will take a medical history and give 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 yet. If necessary, they can refer patients to a fertility clinic or a local hospital for more specialized tests. The results of these tests will help determine which is the best fertility treatment.

Treatment

Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods.

At-home conception kit

In 2007 the FDA cleared the first at home tier one medical conception device to aid in conception. The key to the kit are cervical caps for conception. This at home [cervical cap] insemination method allows all the semen to be placed up against the cervical os for six hours allowing all available sperm to be placed directly on the cervical os. For low sperm count, low sperm motility, or a tilted cervix using a cervical cap will aid in conception. This is a prescriptive medical device.

At-home assessment

Prior to undergoing expensive fertility procedures, many women and couples will turn to online sources to determine their estimate chances of success. A take-home baby assessment can provide a best guess estimate compared with women who have succeeded with in vitro fertilization, based on variables such as maternal age, duration of infertility and number of prior pregnancies.

Medical treatments

Medical treatment of infertility generally involves the use of 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) physicians may start by prescribing a course of ovarian stimulating medication. The physician 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, intrauterine insemination (IUI), in which the doctor 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 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. Recently, a hormone-antioxidant combination therapy was suggested to improve sperm count and motility in infertile men, according to an Egyptian study. Ghanem H et al. Combination clomiphene citrate and antioxidant therapy for idiopathic male infertility: A randomized controlled trial. Fertil Steril 2009 Mar 5; [e-pub ahead of print]. Published in Journal Watch General Medicine March 31, 2009 The study included 60 men who were randomly selected to take either the combination treatment of clomiphene citrate and vitamin E or a placebo for six months. The pregnancy rate was about 37 percent among men who had taken the combination therapy, compared with 13 percent for those in the placebo group. The men in the treatment group also had a greater increase in sperm concentration and an improvement in sperm progression, the Cairo University researchers found. Clomiphene citrate is an anti-estrogen drug designed as a fertility medicine for women but sometimes used to boost sperm production in men with low sperm counts and poor sperm motility. Vitamin E helps counter oxidative stress, which is associated with sperm DNA damage and reduced sperm motility. The results of this study will be encouraging to male factor patients and their doctors, Dr. R. Dale McClure, president of the American Society for Reproductive Medicine, said in a society news release. However, more research is needed to determine how the components of the combination therapy affect the different semen parameters observed and the advantages of using these drugs singly or in combination with other drugs not used in this study.

Complementary and alternative treatments

Three complementary or alternative female infertility treatments have been scientifically tested, with results published in peer-reviewed medical journals.

  1. Group psychological intervention: A 2000 Harvard Medical School study examined the effects of group psychological intervention on infertile women (trying to conceive a duration of one to two years). The two intervention groups a support group and a cognitive behavior group had statistically significant higher pregnancy rates than the control group.

  2. Acupuncture: Acupuncture performed 25 minutes before and after IVF embryo transfer increased IVF pregnancy rates in a German study published in 2002. In a 2006 similar study conducted by The University of South Australia, the acupuncture group s odds (although not statistically significant) were 1.5 higher than the control group. Although definitive results of the effects of acupuncture on embryo transfer remain a topic of discussion, study authors state that it appears to be a safe adjunct to IVF.

  3. Manual physical therapy: The Wurn Technique, a manual manipulative physical therapy treatment, was shown in peer reviewed publications to improve natural and IVF pregnancy rates in infertile women in a 2004 study, and to open and return function to blocked fallopian tubes in a 2008 study. The therapy was designed to address adhesions restricting function and mobility of the reproductive organs.

Ethics

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

  1. High-cost treatments are out of financial reach for some couples.
  2. Debate over whether health insurance companies should be forced to cover infertility treatment.
  3. Allocation of medical resources that could be used elsewhere
  4. The legal status of embryos fertilized in vitro and not transferred in vivo.
  5. Anti-abortion opposition to the destruction of embryos not transferred in vivo.
  6. 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.
  7. Religious leaders` opinions on fertility treatments.
  8. 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.

Many countries have special frameworks for dealing with the ethical and social issues around fertility treatment.

  1. One of the best known is the HFEA The UK`s regulator for fertility treatment and embryo research. This was set up on 1 August 1991 following a detailed commission of enquiry led by Mary Warnock in the 1980s
  2. A similar model to the HFEA has been adopted by the rest of the countries in the European Union. Each country has its own body or bodies responsible for the inspection and lisencing of fertility treatment under the EU Tissues and Cells directive

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 cancer. Even couples undertaking IVF face considerable stress. Emotional stress and marital difficulties are greater in couples where the infertility lies with the man.

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. Some respond by actively avoiding the issue altogether; middle-class men are the most likely to respond in this way There are 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.