Infertility and spontaneous abortion

National Institute for Clinical Excellence. Fertility: assessment and treatment for people with fertility problems [Internet]. London: RCOG Press; 2004 Feb [cited 2009 March 8]. 216 p. Available from: http://www.rcog.org.uk/womens-health/clinical-guidance/fertility-assessment-and-treatment-people-fertility-problems

Recommendations grade A

(Evidence from meta-analysis of randomised controlled trials, or at least one randomised controlled trial)

Initial advice to people concerned about delays in conception

  • Women who smoke should be offered referral to a smoking cessation programme to support their efforts in stopping smoking.
  • Women should be informed that participating in a group programme involving exercise and dietary advice leads to more pregnancies than weight loss advice alone.
  • Women intending to become pregnant should be informed that dietary supplementation with folic acid before conception and up to 12 weeks’ gestation reduces the risk of having a baby with neural tube defects. The recommended dose is 0.4 mg per day. For women who have previously had an infant with a neural tube defect or who are receiving antiepileptic medication, a higher dose of 5 mg per day is recommended.

Investigation of fertility problems and management strategies

  • Where appropriate expertise is available, screening for tubal occlusion using hysterosalpingo-contrast-ultrasonography should be considered because it is an effective alternative to hysterosalpingography for women who are not known to have co-morbidities.
  • The routine use of post-coital testing of cervical mucus in the investigation of fertility problems is not recommended because it has no predictive value on pregnancy rate.

Medical and surgical management of male factor fertility problems

  • Men with idiopathic semen abnormalities should not be offered anti-oestrogens, gonadotrophins, androgens, bromocriptine or kinin-enhancing drugs because they have not been shown to be effective.
  • Men should be informed that the significance of antisperm antibodies is unclear and the effectiveness of systemic corticosteroids is uncertain.
  • Men with leukocytes in their semen should not be offered antibiotic treatment unless there is an identified infection because there is no evidence that this improves pregnancy rates.
  • Men should not be offered surgery for varicoceles as a form of fertility treatment because it does not improve pregnancy rates.

Ovulation induction

  • Women with World Health Organization Group II ovulation disorders (hypothalamic pituitary dysfunction) such as polycystic ovary syndrome should be offered treatment with clomifene citrate (or tamoxifen) as the first line of treatment for up to 12 months because it is likely to induce ovulation.
  • Women with unexplained fertility problems should be informed that clomifene citrate treatment increases the chance of pregnancy, but that this needs to be balanced by the possible risks of treatment, especially multiple pregnancy.
  • Anovulatory women with polycystic ovary syndrome who have not responded to clomifene citrate and who have a body mass index of more than 25 should be offered metformin combined with clomifene citrate because this increases ovulation and pregnancy rates.
  • Women with polycystic ovary syndrome who have not responded to clomifene citrate should be offered laparoscopic ovarian drilling because it is as effective as gonadotrophin treatment and is not associated with an increased risk of multiple pregnancy.
  • Women with World Health Organization Group II ovulation disorders such as polycystic ovary syndrome who do not ovulate with clomifene citrate (or tamoxifen) can be offered treatment with gonadotrophins. Human menopausal gonadotrophin, urinary follicle-stimulating hormone and recombinant follicle-stimulating hormone are equally effective in achieving pregnancy and consideration should be given to minimising cost when prescribing.
  • Women with World Health Organization Group II ovulation disorders such as polycystic ovary syndrome who ovulate with clomifene citrate but have not become pregnant after 6 months of treatment should be offered clomifene citrate-stimulated intra-uterine insemination.
  • Human menopausal gonadotrophin, urinary folliclestimulating hormone and recombinant follicle-stimulating hormone are equally effective in achieving a live birth when used following pituitary down-regulation as part of in vitro fertilisation treatment. Consideration should be given to minimising cost when prescribing.
  • Women with polycystic ovary syndrome who are being treated with gonadotrophins should not be offered treatment with gonadotrophin-releasing hormone agonist concomitantly because it does not improve pregnancy rates, and it is associated with an increased risk of ovarian hyperstimulation.
  • For pituitary down-regulation as part of in vitro fertilisation treatment, using gonadotrophin-releasing hormone agonist in addition to gonadotrophin stimulation facilitates cycle control and results in higher pregnancy rates than the use of gonadotrophins alone. The routine use of gonadotrophin-releasing hormone agonist in long protocols during in vitro fertilisation is therefore recommended.
  • The use of gonadotrophin-releasing hormone antagonists is associated with reduced pregnancy rates and is therefore not recommended outside a research context.
  • The use of adjuvant growth hormone treatment with gonadotrophin-releasing hormone agonist and/or human menopausal gonadotrophin during ovulation induction in women with polycystic ovary syndrome who do not respond to clomifene citrate is not recommended because it does not improve pregnancy rates.
  • The effectiveness of pulsatile gonadotrophin-releasing hormone in women with clomifene citrate-resistant polycystic ovary syndrome is uncertain and is therefore not recommended outside a research context.
  • Women with ovulatory disorders due to hyperprolactinaemia should be offered treatment with dopamine agonists such as bromocriptine. Consideration should be given to safety for use in pregnancy and minimising cost when prescribing.

Medical and surgical management of endometriosis

  • Medical treatment of minimal and mild endometriosis does not enhance fertility in subfertile women and should not be offered.
  • Women with minimal or mild endometriosis who undergo laparoscopy should be offered surgical ablation or resection of endometriosis plus laparoscopic adhesiolysis because this improves the chance of pregnancy.
  • Women with ovarian endometriomas should be offered laparoscopic cystectomy because this improves the chance of pregnancy.
  • Post-operative medical treatment does not improve pregnancy rates in women with moderate to severe endometriosis and is not recommended.

Intra-uterine insemination

  • Couples with mild male factor fertility problems, unexplained fertility problems or minimal to mild endometriosis should be offered up to six cycles of intra-uterine insemination because this increases the chance of pregnancy.
  • Where intra-uterine insemination is used to manage male factor fertility problems, ovarian stimulation should not be offered because it is no more clinically effective than unstimulated intra-uterine insemination and it carries a risk of multiple pregnancy.
  • Where intra-uterine insemination is used to manage unexplained fertility problems, both stimulated and unstimulated intra-uterine insemination are more effective than no treatment. However, ovarian stimulation should not be offered, even though it is associated with higher pregnancy rates than unstimulated intra-uterine insemination, because it carries a risk of multiple pregnancy.
  • Where intra-uterine insemination is used to manage minimal or mild endometriosis, couples should be informed that ovarian stimulation increases pregnancy rates compared with no treatment, but that the effectiveness of unstimulated intra-uterine insemination is uncertain.
  • Where intra-uterine insemination is undertaken, single rather than double insemination should be offered.
  • Where intra-uterine insemination is used to manage unexplained fertility problems, fallopian sperm perfusion for insemination (a large-volume solution, 4 ml) should be offered because it improves pregnancy rates compared with standard insemination techniques.

Factors affecting the outcome of in vitro fertilisation treatment

  • Women with hydrosalpinges should be offered salpingectomy, preferably by laparoscopy, before in vitro fertilisation treatment because this improves the chance of a live birth.
  • There is insufficient evidence to recommend the use of gamete intrafallopian transfer or zygote intrafallopian transfer in preference to in vitro fertilisation in couples with unexplained fertility problems or male factor fertility problems.

Procedures used during in vitro fertilisation treatment

  • Natural cycle in vitro fertilisation has lower pregnancy rates per cycle of treatment than clomifene citratestimulated and gonadotrophin-stimulated in vitro fertilisation and is therefore not recommended, except in the rare circumstances where gonadotrophin use is contraindicated.
  • The use of adjuvant growth hormone with gonadotrophins during in vitro fertilisation cycles does not improve pregnancy rates and is therefore not recommended.
  • Couples should be informed that, in effecting oocyte maturation, recombinant human chorionic gonadotrophin achieves similar results to urinary human chorionic gonadotrophin in terms of pregnancy rates and incidence of ovarian hyperstimulation syndrome. Consideration should be given to minimising cost when prescribing.
  • Monitoring oestrogen levels during ovulation induction as part of in vitro fertilisation treatment is not recommended as a means of improving in vitro fertilisation treatment success rates because it does not give additional information with regard to live birth rates or pregnancy rates compared with ultrasound monitoring.
  • Women who have a significant risk of developing ovarian hyperstimulation syndrome should not be offered oocyte maturation (or luteal support) using human chorionic gonadotrophin.
  • Women undergoing transvaginal retrieval of oocytes should be offered conscious sedation because it is a safe and acceptable method of providing analgesia.
  • Women who have developed at least three follicles before oocyte retrieval should not be offered follicle flushing because this procedure does not increase the numbers of oocytes retrieved or pregnancy rates, and it increases the duration of oocyte retrieval and associated pain.
  • Assisted hatching is not recommended because it has not been shown to improve pregnancy rates.
  • Women undergoing in vitro fertilisation treatment should be offered ultrasound-guided embryo transfer because this improves pregnancy rates.
  • Women should be informed that bed rest of more than 20 minutes’ duration following embryo transfer does not improve the outcome of in vitro fertilisation treatment.
  • Women who are undergoing in vitro fertilisation treatment using gonadotrophin-releasing hormone agonists for pituitary down-regulation should be informed that luteal support using human chorionic gonadotrophin or progesterone improves pregnancy rates.
  • The routine use of human chorionic gonadotrophin for luteal support is not recommended because of the increased likelihood of ovarian hyperstimulation syndrome.

Intracytoplasmic sperm injection

  • Couples should be informed that intracytoplasmic sperm injection improves fertilisation rates compared to in vitro fertilisation alone, but once fertilisation is achieved the pregnancy rate is no better than with in vitro fertilisation.

Donor insemination

  • Couples using donor sperm should be offered intra-uterine insemination in preference to intra-cervical insemination because it improves pregnancy rates.

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Edited by Aldo Campana,