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AilaTiitinen

Infertility

Essentials

  • Approximately 15% of all couples suffer from infertility at some point during their lives.
  • In most cases, the couple experiences diminished fertility (subfertility), i.e. it takes more than one year to conceive. Sterility denotes complete infertility, which is rare.
  • 80-85% of couples engaging in sexual relations without contraception will conceive within one year, if the woman is younger than 38 years of age. Of the remainder, half will conceive without treatment within the following year.
  • In about 25% of cases, infertility is caused by a female factor and in about 25% by a male factor. An infertility-causing factor is identified in both partners in about 25% of cases, and in the remaining 25% the reason for infertility remains unknown.
  • The initial infertility investigations are carried out in primary health care.
  • Assisted reproduction treatments can be used with good results in almost all causes or infertility.

Causes

  • The most common causes of infertility are ovulatory dysfunction (20-30%), tubal problems (tubal factor infertility; 10-15%), endometriosis (10-20%) and poor quality sperm (20-40%). More rare are problems originating from the uterus and sexual dysfunction. Some of the causes of subfertility will become apparent only after treatment is commenced.
  • Poorly managed systemic illnesses (e.g. diabetes, epilepsy, inflammatory bowel diseases, coeliac disease) may reduce fertility.
  • Pharmacotherapies may disturb ovary function.
    • NSAIDs, for example, may impair ovulation and embryo implantation.
    • Cytostatic therapies and lower abdominal radiotherapy are associated with the risk of ovarian damage.
  • Being overweight or underweight reduces, in particular, female fertility. At the same time the risk of miscarriage increases. Obesity decreases the quality of semen.
  • Excessive smoking impairs the functioning of the ovaries and reduces the quality of sperm.
  • Daily heavy alcohol consumption may disturb the production of sperm and may also reduce female fertility.
  • Some pharmaceuticals, such as testosterone therapy, cytostatic drugs, some antihypertensive drugs (calcium channel blockers) and long-acting sulpha drugs may hamper sperm production.
    • Anabolic steroids reduce sperm production in most users and may lead to a complete absence of sperm (azoospermia).
    • The role of occupational exposure is usually difficult to assess.

Causes of female infertility

Causes of male infertility

  • Undescended testes
  • History of orchitis
  • Varicocele
  • Hormonal causes
    • Hypogonadotropic hypogonadism
  • Genetic causes
    • Sex chromosome changes
    • Y chromosome deletions
    • Chromosome translocations
  • Occlusion of the epididymides or vasa deferetia
  • Sperm antibodies
  • Structural abnormalities of sperm
  • Sexual problems
    • Ejaculatory dysfunction
    • Impotence

Investigations

  • Investigations are started after one year of unprotected intercourse without conception. It is also possible to start the investigations earlier if the couple have a relevant history (e.g. amenorrhoea).
  • The general practitioner should obtain a medical history and carry out preliminary investigations based on which the couple may be referred for further investigations to a clinic specialized in the management of infertility. Private infertility clinics do not require a referral.
  • If either or both of the couple are abusing alcohol and/or drugs, or if they have underlying illnesses, nutritional problems or mental health problems, these should be addressed already within primary care.
  • If the woman is on continuous medication, its safety during pregnancy should be checked.

First stage (health centre, other primary health care facility)

  • The investigations are commenced, if possible, at the same time for both partners, and all preliminary investigations must be carried out (one cause does not exclude another).
    • The general health of both partners as well as their gynaecological and sexual history should be charted.
    • Any underlying illnesses, medication in use and the couple's psychosocial situation should be found out.
    • The extent and urgency of investigations is dependent on the medical history and clinical findings.
    • The aim is to evaluate whether the woman is ovulating, is the uterus healthy, are the Fallopian tubes patent and is the quality of sperm adequate.
  • Clinical examination is the most important investigation; the patient's appearance and build give a great deal of information about the hormonal state.
    • Blood pressure, height, weight, growth of body hair and secondary sexual characteristics are recorded.
    • Basic blood count with platelets, TSH, free T4 and other basic laboratory investigations as indicated, e.g. fasting blood glucose are determined.
    • A sample should be collected, if indicated, from the woman for a Pap smear and a Chlamydia test during the gynaecological examination, if there are symptoms or signs of an infection or a history of earlier infections.
  • An irregular menstrual cycle is an indication for further investigations based on other symptoms (e.g. measurement of prolactin, FSH).
  • The first-line investigation for men is semen analysis.
  • If the semen analysis is abnormal or the man has symptoms around his genital organs, a clinical examination is warranted.
    • Small and soft testes are clearly indicative of irreversible testicular disorder.
    • A varicocele Surgery or Embolisation for Varicocele in Subfertile Men is usually on the left side and is seen above the testis as soft bluish vascular dilatation.
    • A testicular ultrasound will reveal any structural defects or tumours.

Second stage (infertility clinic, a hospital outpatient clinic)

  • Before infertility treatment is commenced, the couple must be screened for infections (hepatitis B and C, HIV).
  • A vaginal ultrasound examination gives information about the structure of the female reproductive organs and the functioning of ovaries. In unclear cases, normal saline may be instilled into the uterine cavity to assess the evaluation (hysterosonography, HSG). A mixture of air and water may be instilled into the uterus in order to assess tubal patency (hysterosalpingosonography, HSSG).
  • If the result of HSSG is abnormal, or there is a suspicion of endometriosis Laparoscopic Surgery for Subfertility Associated with Endometriosis or the patient has a history of an inflammatory condition, laparoscopy is indicated.
  • Gonadotropin levels are checked during early cycle if the cycles are irregular. AMH (anti-Müllerian hormone) concentration gives a picture of the ovarian reserve.
  • Other hormone determinations are warranted if an endocrine disorder is suspected.
  • Monitoring of the growth of the ovarian follicle gives information on ovulation. Progesterone assay during the end-cycle is used, as necessary, to confirm the ovulation and the sufficient activity of the corpus luteum.
  • Semen analysis (if not yet done within primary care or if it has been abnormal)
    • If the result is normal, further investigations are usually not needed.
    • The result of semen analysis may vary significantly according to the collection time, and an abnormal result should be rechecked after a couple of months.
    • The sperm density should be HASH(0x2f82cc8) 15 million sperm/ml, the total sperm count HASH(0x2f82cc8) 39 million and the ejaculate volume > 1.5 ml. The sample is considered normal if over 25% of sperm move forward or over 32% of sperm are motile, and the total proportion of motile sperm is HASH(0x2f82cc8) 40%.
    • Strict criteria are used to evaluate sperm morphology, but the significance of sperm morphology during initial investigations is unclear. Sperm antibodies are also determined during semen analysis (MAR, Mixed Antiglobulin Reaction test).
  • Follow-up investigations are indicated for the man if semen analysis is repeatedly abnormal (FSH, LH, testosterone, karyotype, Y chromosome microdeletion)
    • In men, hormonal causes are rarely the cause of infertility.
    • FSH concentration should be determined if no sperm are present in the semen, or their number is markedly reduced. An increased FSH concentration is suggestive of a testicular defect and chromosome assays are indicated. Klinefelter's syndrome or various translocations may be identified. Y chromosome microdeletions cause serious disturbances in the formation of sperm.
    • Normal FSH concentration and normal testes are suggestive of occluded seminiferous tubules. The diagnosis may be confirmed with testicular biopsy.

Treatment Tubal Flushing for Subfertility, Intrauterine Insemination with Ovarian Hyperstimulation Vs. Expectant Management for Unexplained Subfertility, Timed Intercourse for Couples Trying to Conceive

  • Treatment is planned according to the underlying cause, taking into account the wishes of the couple.
  • In the case of ovulatory dysfunction the treatment results are good, provided that the diagnosis is correct.
    • An underlying endocrine disease, e.g. hypothyroidism, must be treated.
    • If ovulatory dysfunction is caused by being underweight or overweight, normal weight should be attained before drug treatment is commenced.
    • Hyperprolactinaemia can be successfully treated with medication.

Hormone treatment Risk of Ovarian Cancer Associated with Ovulation Induction, Metformin Treatment Before and during Ivf or Icsi in Women with Polycystic Ovary Syndrome, Aromatase Inhibitors (Letrozole) for Infertile Women with Polycystic Ovary Syndrome

Surgical approach Surgical Treatment of Tubal Disease in Women Due to Undergo in Assisted Reproductive Technology, Laparoscopic Surgery for Subfertility Associated with Endometriosis, Surgical Treatment of Fibroids for Subfertility

Insemination and in vitro fertilisation , Number of Embryos for Transfer Following in-Vitro Fertilisation or Intra-Cytoplasmic Sperm Injection, Metformin Treatment Before and during Ivf or Icsi in Women with Polycystic Ovary Syndrome, Single Versus Double Intrauterine Insemination (Iui) in Stimulated Cycles for Subfertile Couples, Intra-Uterine Insemination for Unexplained Subfertility, Efficacy of in Vitro Fertilization and Embryo Transfer

  • The reasons behind poor quality sperm are often not known and, therefore, treatment forms to manage male subfertility are few. If the quality of sperm is only moderately affected insemination or in vitro fertilisation is used.
  • During intra-uterine insemination (IUI), sperm are injected into the uterine cavity. Before insemination the sperm must be separated (”washed”) from seminal plasma. The chance of pregnancy is usually improved by inducing ovulation during the cycle Intra-Uterine Insemination for Unexplained Subfertility.
  • In vitro fertilisation Efficacy of in Vitro Fertilization and Embryo Transfer, using either the couple's own sperm or donor sperm, may be used in almost all types of infertility. During the last few years, intracytoplasmic sperm injection (ICSI) has become the treatment of choice in male infertility. The results of IVF and ICSI treatments are dependent on the age of the woman, the reason for treatment, previous fertility history and the number of treatment attempts.
  • Find out about the local availability of assisted reproduction treatments with donated gametes in primary health care and about relevant local policies and guidance.

Ovarian hyperstimulation syndrome as a complication Dopamine Agonists for Preventing Ovarian Hyperstimulation Syndrome

  • Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of infertility treatment.
    • In OHSS, the response of the ovaries to hormone medication is excessive.
    • OHSS is most common in in vitro fertilization therapy when a gonadotropin-releasing hormone (GnRH) analogue has been used with gonadotropins.
    • The symptoms usually start 3-10 days after the induction of ovulation (the administration of human chronionic gonadotropin, hCG).
    • Symptoms include abdominal pain, swelling and nausea.
    • The risk is increased in women aged less than 35 years and in women with low body weight or polycystic ovaries.
    • If OHSS is suspected, ovarian ultrasound examination is the first-line investigation Gynaecological Ultrasound Examination; the diameter of the ovaries is usually more than 8 cm, and in severe hyperstimulation, fluid is present in the abdominal cavity.
    • An early referral to a hospital, or to the care of the treating specialist, is indicated.
    • Severe OHSS may be associated with thromboembolic complications, breathing difficulties or renal insufficiency.

Prevention of infertility

  • Reproductive health may be improved by the prevention and optimal treatment of chlamydial infection, maintaining normal body weight, recognising the effect of age on fertility and by refraining from smoking. In addition to measures taken to encourage healthy lifestyles, sex and fertility education at schools and further education facilities should be increased.
  • A woman planning pregnancy should follow a well-balanced diet. A basically healthy woman does usually not need particular dietary supplements. Vitamin B12 is recommended for women following strict vegetarian diet. Folic acid 400 µg/day and vitamin D 10-20 µg/day are recommended for all. Multivitamin products are not harmful if used according to instructions.

Psychosocial issues

  • Infertility will unavoidably raise various feelings: shame, grief and feelings of worthlessness and humiliation. Feelings of worthlessness are common as is resentfulness that outside help is needed with the most intimate part of the couple's life. It is difficult to cope with the sorrow and anguish caused by childlessness. Both partners should be encouraged, either together or separately, to seek new interests in life.
  • Almost everyone faced with involuntary childlessness will undergo an infertility crisis of some degree. Having to abandon the hope of having a child will trigger a crisis. The person will need to be allowed to mourn; remaining childless may be compared to the grief caused by a death of a close relative. An involuntarily childless person loses the unborn children who had lived in his/her imagination. There is no definite starting point to the crisis, and the couple may face it at different times. Likewise, the end of the crisis is gradual.
  • Infertility treatment is demanding both physically and psychologically. Despite the treatment aiming towards a positive outcome the couple may find it difficult to persevere with it, and this may produce conflicting feelings which will only add to the underlying problem of infertility. The couple may be asked to take difficult decisions which will have far reaching consequences as regards their own lives and that of a child born as the result of the treatment, for example when donor sperm treatment is considered. However, modern treatment modalities do bring hope and help most couples to conceive.
  • The most difficult task faced by an infertility specialist is the stopping of treatment. All treatment and investigations carried out must be carefully reviewed and explained to the couple. At the same time, the possible reasons for treatment failure should be evaluated and the likelihood of a later pregnancy without further treatment should also be estimated. If the couple so wish, they should be given information about the possibility of adopting a child. After treatment failure, it must be assessed whether the couple is in need of psychological support and counselling.
  • Infertility is a psychosocial problem, and when faced with it the health care provider must not concentrate only on the medical aspects of the problem. Professional expertise is necessary in order to help with possible sexual problems as well as feelings of guilt, anger, grief and loss.
  • Peer group support may be significant. Peer groups welcome couples going through infertility investigations and treatment, those who have either conceived a child as a result of treatment or have adopted a child, couples who have started the adoption process and those who have decided to remain childless.

Evidence Summaries ⬆