Fertility

Assessment and treatment for people with fertility problems

Clinical practice algorithm

February 2004 Developed by the National Collaborating Centre for Womens and Childrens Health

Assessment and treatment for people with fertility problems

Infertility: Failure to conceive after regular unprotected sexual intercourse for 2 years in the absence of known reproductive pathology
This guideline does not include the management of people who are outside this definition, such as those with sexual dysfunction, couples who are using contraception and couples outside the reproductive age range.

Initial advice for people concerned about delays in conception: Cumulative probability of pregnancy in general population: 84% in 1st year 92% in 2nd year Fertility declines with a womans age Lifestyle advice: Sexual intercourse every 23 days 12 units alcohol/week for women; 34 units/week for men Smoking cessation programme for smokers Body mass index of 1929 Information about prescribed, over-the-counter and recreational drugs Information about occupational hazards Offer preconceptional advice: Folic acid Rubella susceptibility and cervical screening Early investigation if: History of predisposing factors (such as amenorrhoea, oligomenorrhoea, pelvic inflammatory disease or undescended testes); womans age 35 yrs; people with HIV, hepatitis B and hepatitis C; prior treatment for cancer People preparing for cancer treatment: Follow Royal College of Physicians and Royal College of Radiologists guidance Cryostorage of gametes and/or embryos

Principles of care: Couple-centred management Access to evidence-based information (verbal and written) Counselling from someone not directly involved in management of the couples fertility problems Contact with fertility support groups Specialist teams

Clinical investigation of fertility problems and management strategies

Female Assessment of ovulation:
Check for frequency and regularity of menstrual cycles

For people who have not conceived after 1 year of regular unprotected sexual intercourse

Male

Semen analysis: If irregular:

Day 21 serum progesterone if 28 day cycle or later in long cycle to confirm ovulation Serum gonadotrophins (FSH and LH) Serum prolactin unless galactorrhoea or pituitary tumour Inhibin B Thyroid function test unless symptoms of thyroid disease Endometrial biopsy Irregular ovulation If regular ovulation, see Unexplained infertility

Tests for tubal occlusion:

The results of semen analysis and assessment of ovulation should be known before a test for tubal patency is performed. Screening for Chlamydia trachomatis before uterine examination or offer prophylactic antibiotics HSG/hysterosalpingo-contrast-ultrasonography if no history of co-morbidity (endometriosis/pelvic inflammatory disease/ ectopic pregnancy) Laparoscopy and dye if history of co-morbidity

If occlusion Consider in vitro fertilisation

Tubal surgery if mild tubal disease Tubal catheterisation or cannulation if proximal occlusion

Compare with WHO reference values: Volume 2.0 ml Liquefaction time within 60 minutes pH 7.2 Sperm concentration 20 x 106 per ml Total sperm number 40 x 106 spermatozoa per ejaculate Motility 50% (grades a and b) or 25% with progressive motility (grade a) within 60 minutes of ejaculation Vitality 75% live White blood cells: < 106 per ml Morphology: 15% or 30% Screening for anti-sperm antibodies Ideally repeat after 3 months if abnormal or as soon as possible if gross sperm deficiency

If normal Unexplained fertility problems

(Normal semen analysis, no ovulation disorders, no tubal occlusion):

WHO group I (hypothalamic pituitary failure):

Gonadotrophins with LH activity or pulsatile GnRH

If abnormal

If normal, see

Unexplained infertility

WHO group II (hypothalamic pituitary dysfunction, mainly polycystic ovary syndrome):

Clomifene citrate* or tamoxifen* (up to 12 months if ovulating) with ultrasound monitoring during at least the first cycle to adjust dose

Hypogonadotrophic hypogonadism:

Minimal/mild endometriosis:

Gonadotrophins

Mild male factor fertility problems:

Surgical ablation or resection and adhesiolysis at laparoscopy

Obstructive azoospermia:

If ovulating but not pregnant after 6 months:

Offer clomifene citrate* plus intra-uterine insemination

Surgery Sperm recovery

Unstimulated intrauterine insemination x 6 cycles

If no pregnancy:

Clomifene citrate Unstimulated intra-uterine insemination x 6 cycles Fallopian sperm perfusion Stimulated intra-uterine insemination x 6 cycles with ultrasound monitoring with risk of OHSS and multiple pregnancy

If no ovulation with clomifene citrate:

Metformin plus clomifene citrate* or hMG*, uFSH* or rFSH* with ultrasound monitoring or Ovarian drilling

Varicoceles:

Moderate/severe endometriosis: Hyperprolactinaemia:

Bromocriptine
* Risk of OHSS and multiple pregnancy

Ejaculatory failure:

Surgery

Surgery

Drug therapy Sperm recovery

Endometriomas:

Laparoscopic cystectomy

If no pregnancy with azoospermia, bilateral tubal occlusion or 3 years infertility and the woman is aged 2339 years, offer up to 3 stimulated cycles of in vitro fertilisation treatment
Procedures for in vitro fertilisation treatment: 1. Offer screening:
HIV, hepatitis B, hepatitis C; specialist referral if positive

Additional principles of care for people undergoing in vitro fertilisation treatment: 2. Ovulation induction:

Access to evidence-based information (verbal and written) on risks/implications of assisted reproduction, including health of resulting children; genetic counselling; consideration of welfare of the child

3. Embryo transfer:
No more than 2 embryos to be transferred during any 1 cycle Offer cryostorage of supernumerary embryos if more than 2 embryos Frozen embryos to be transferred before further stimulated cycles Ultrasound-guided embryo transfer on day 2 or 3, or on day 5 or 6

Factors affecting the outcome of in vitro fertilisation treatment:

4. Luteal support:
Progesterone

Natural cycle Pituitary down-regulation with GnRH agonist long protocol GnRH agonist with gonadotrophins with consideration to minimising cost GnRH antagonists Growth hormone adjuvant Monitor follicular development with ultrasound: clinics should have protocols for management of OHSS Oocyte maturation with human chorionic gonadotrophins Oocyte retrieval: offer conscious sedation (follow Academy of Medical Royal Colleges guidance) Follicle flushing Assisted hatching

Salpingectomy before in vitro fertilisation treatment for women with hydrosalpinges Optimal womans age is 2339 years at time of treatment Increased success with previous pregnancy and/or live birth Ideal body mass index is 1930 Increased success with low alcohol/caffeine intake Increased success in non-smokers Consistent for first 3 cycles of treatment, effectiveness after 3 cycles is uncertain

Women should be informed of the risks of OHSS and multiple pregnancy

Management options associated with in vitro fertilisation treatment and other forms of assisted reproduction
Donor insemination:
Time insemination with either urinary luteinising hormone or basal body temperature changes If regular ovulation, offer 6 unstimulated cycles

Intracytoplasmic sperm injection for couples with:

Donor insemination for couples with:

Oocyte donation for women with:

Premature ovarian failure Gonadal dysgenesis including Turner syndrome Bilateral oophorectomy Ovarian failure following chemotherapy or radiotherapy Certain cases of in vitro fertilisation treatment failure Genetic disorder transmission to offspring

Severe semen quality deficits Azoospermia Poor in vitro fertilisation treatment response

Azoospermia Genetic/infectious disease in male partner Severe rhesus isoimmunisation Severe semen deficits

Screening:

Screening of sperm donors:

Oocyte donors: Screening of oocyte donors:

Follow Human Fertilisation and Embryology Authority guidance Risks of ovarian stimulation and oocyte collection Egg sharing: counselling

Male karyotype

Follow British Andrology Society guidance

Assessment of female partner:

Confirm ovulation HSG if no pregnancy after 3 cycles

This algorithm should, where necessary, be interpreted with reference to the full guideline

Key: FSH follicle-stimulating hormone; GnRH gonadotrophin-releasing hormone; HIV human immunodeficiency virus; hMG human menopausal gonadotrophin; HSG hysterosalpingography; LH luteinising hormone; OHSS ovarian hyperstimulation syndrome; rFSH recombinant FSH; uFSH urinary FSH; WHO World Health Organization

Clinical Guideline 11 Fertility Assessment and treatment for people with fertility problems Issue date: February 2004 The algorithm on this poster forms part of the NICE guideline on fertility (see above). Copies of the NICE guideline can be obtained free of charge from the NICE website (www.nice.org.uk) and from the NHS Response Line (phone 0870 1555 455 and quote reference number N0465). A version for people who want to understand what NICE has told the NHS, called Assessment and treatment for people with fertility problems, is also available from the Response Line; quote reference number N0466 for an English only version and N0467 for an English and Welsh version.

Information on the full guideline produced by the National Collaborating Centre for Womens and Childrens Health, from which the NICE guideline has been prepared, is given in Section 5 of the NICE guideline.

This guidance is written in the following context: This guidance represents the view of the Institute, which was arrived at after careful consideration of the evidence available. Health professionals are expected to take it fully into account when exercising their clinical judgement. The guidance does not, however, override the individual responsibility of health professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.

National Institute for Clinical Excellence

MidCity Place 71 High Holborn London WC1V 6NA www.nice.org.uk Copyright National Institute for Clinical Excellence, February 2004. All rights reserved. This material may be freely reproduced for educational and not-for-profit purposes within the NHS. No reproduction by or for commercial organisations is allowed without the express written permission of the National Institute for Clinical Excellence. ISBN: 1-84257-546-5 Published by the National Institute for Clinical Excellence, February 2004 Artwork by LIMA Graphics Ltd, Frimley, Surrey Printed by Abba Litho Limited, London

N0465 1P 80k Feb 04 (ABA)