Evidence categories (1a-4) and recommendation grades (A-D) are defined at the end of the "Major Recommendations" field.
In addition to evidence-based recommendations, the guideline development group (GDG) also identifies good practice points (GPP).
Initial Advice to People Concerned about Delays in Conception
Natural conception
D - People who are concerned about their fertility should be informed that about 84% of couples in the general population will conceive within 1 year if they do not use contraception and have regular sexual intercourse. Of those who do not conceive in the first year, about half will do so in the second year (cumulative pregnancy rate 92%).
C - People who are concerned about their fertility should be informed that female fertility declines with age, but that the effect of age on male fertility is less clear. With regular unprotected sexual intercourse, 94% of fertile women aged 35 years, and 77% of those aged 38 years, will conceive after 3 years of trying.
Frequency and timing of sexual intercourse
C - People who are concerned about their fertility should be informed that sexual intercourse every 2 to 3 days optimises the chance of pregnancy. Timing intercourse to coincide with ovulation causes stress and is not recommended.
Alcohol
D - Women who are trying to become pregnant should be informed that drinking no more than one or two units of alcohol once or twice per week and avoiding episodes of intoxication reduces the risk of harming a developing fetus.
GPP - Men should be informed that alcohol consumption within the Department of Health's recommendations of three to four units per day for men is unlikely to affect their fertility.
B - Men should be informed that excessive alcohol intake is detrimental to semen quality.
Smoking
B - Women who smoke should be informed that this is likely to reduce their fertility.
A - Women who smoke should be offered referral to a smoking cessation programme to support their efforts in stopping smoking.
B - Women should be informed that passive smoking is likely to affect their chance of conceiving.
GPP - Men who smoke should be informed that there is an association between smoking and reduced semen quality (although the impact of this on male fertility is uncertain), and that stopping smoking will improve their general health.
Caffeinated beverages
B - People who are concerned about their fertility should be informed that there is no consistent evidence of an association between consumption of caffeinated beverages (tea, coffee and colas) and fertility problems.
Body weight
B - Women who have a body mass index of more than 29 should be informed that they are likely to take longer to conceive.
B - Women who have a body mass index of more than 29 and who are not ovulating should be informed that losing weight is likely to increase their chance of conception.
A - Women should be informed that participating in a group programme involving exercise and dietary advice leads to more pregnancies than weight loss advice alone.
C - Men who have a body mass index of more than 29 should be informed that they are likely to have reduced fertility.
B - Women who have a body mass index of less than 19 and who have irregular menstruation or are not menstruating should be advised that increasing body weight is likely to improve their chance of conception.
Tight underwear for men
B - Men should be informed that there is an association between elevated scrotal temperature and reduced semen quality, but that it is uncertain whether wearing loose-fitting underwear improves fertility.
Occupation
B - Some occupations involve exposure to hazards that can reduce male or female fertility, and therefore a specific enquiry about occupation should be made to people who are concerned about their fertility and appropriate advice should be offered.
Prescribed, over-the-counter and recreational drug use
B - A number of prescription, over-the-counter and recreational drugs interfere with male and female fertility, and therefore a specific enquiry about these should be made to people who are concerned about their fertility and appropriate advice should be offered.
Complementary therapy
GPP - People who are concerned about their fertility should be informed that the effectiveness of complementary therapies for fertility problems has not been properly evaluated and that further research is needed before such interventions can be recommended.
Folic acid supplementation
A - 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.
Susceptibility to rubella
D - Women who are concerned about their fertility should be offered rubella susceptibility screening so that those who are susceptible to rubella can be offered rubella vaccination. Women who are susceptible to rubella should be offered rubella vaccination and advised not to become pregnant for at least 1 month following vaccination.
Cervical cancer screening
GPP - To avoid delay in fertility treatment a specific enquiry about the timing and result of the most recent cervical smear test should be made to women who are concerned about their fertility. Cervical screening should be offered in accordance with the national cervical screening programme guidance.
Defining Infertility, Assessment and Referral
Defining infertility
D - Infertility should be defined as failure to conceive after regular unprotected sexual intercourse for 2 years in the absence of known reproductive pathology.
Assessment and referral
GPP - People who are concerned about delays in conception should be offered an initial assessment. A specific enquiry about lifestyle and sexual history should be taken to identify people who are less likely to conceive.
GPP - The environment in which investigation of fertility problems takes place should enable people to discuss sensitive issues such as sexual abuse.
GPP - People who have not conceived after 1 year of regular unprotected sexual intercourse should be offered further clinical investigation including semen analysis and/or assessment of ovulation.
GPP - Where there is a history of predisposing factors (such as amenorrhoea, oligomenorrhoea, pelvic inflammatory disease, or undescended testes), or where a woman is aged 35 years or over, earlier investigation should be offered.
GPP - Where there is a known reason for infertility (such as prior treatment for cancer), early specialist referral should be offered.
GPP - People who are concerned about their fertility and who are known to have chronic viral infections such as hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) should be referred to centres that have appropriate expertise and facilities to provide safe risk-reduction investigation and treatment.
Principles of Care
Information giving and couple-centred management
C - Couples who experience problems in conceiving should be seen together because both partners are affected by decisions surrounding investigation and treatment.
C - People should have the opportunity to make informed decisions regarding their care and treatment via access to evidence-based information. These choices should be recognised as an integral part of the decision-making process. Verbal information should be supplemented with written information or audio-visual media.
GPP - Information regarding care and treatment options should be provided in a form that is accessible to people who have additional needs, such as people with physical, cognitive, or sensory disabilities, and people who do not speak or read English.
Psychological effects of fertility problems
C - Couples should be informed that stress in the male and/or female partner can affect the couple's relationship and is likely to reduce libido and frequency of intercourse, which can contribute to fertility problems.
GPP - People who experience fertility problems should be informed that they may find it helpful to contact a fertility support group.
C - People who experience fertility problems should be offered counselling because fertility problems themselves and the investigation and treatment of fertility problems can cause psychological stress.
GPP - Counselling should be offered before, during, and after investigation and treatment, irrespective of the outcome of these procedures.
GPP - Counselling should be provided by someone who is not directly involved in the management of the couple's fertility problems.
Specialist and generalist care
D - People who experience fertility problems should be treated by a specialist team because this is likely to improve the effectiveness and efficiency of treatment and is known to improve patient satisfaction.
Investigation of Fertility Problems and Management Strategies
Semen analysis
GPP - The results of semen analysis conducted as part of an initial assessment should be compared to the following World Health Organization reference values:
- Volume: 2.0 ml or more
- Liquefaction time: within 60 minutes
- pH: 7.2 or more
- Sperm concentration: 20 million spermatozoa per mL or more
- Total sperm number: 40 million spermatozoa per ejaculate or more
- Motility: 50% or more motile (grades a* and b**) or 25% or more with progressive motility (grade a) within 60 minutes of ejaculation
* Grade a: rapid progressive motility (sperm moving swiftly, usually in a straight line).
** Grade b: slow or sluggish progressive motility (sperm may be less linear in their progression).
- Vitality: 75% or more live
- White blood cells: fewer than 1 million per mL
- Morphology: 15% or 30%***
*** Currently being reassessed by the World Health Organization. In the interim, the proportion of normal forms accepted by laboratories in the United Kingdom (UK) is either the earlier World Health Organization lower limit of 30% or 15% based on strict morphological criteria.
GPP - Screening for antisperm antibodies should not be offered because there is no evidence of effective treatment to improve fertility.
B - If the result of the first semen analysis is abnormal, a repeat confirmatory test should be offered.
GPP - Repeat confirmatory tests should ideally be undertaken 3 months after the initial analysis to allow time for the cycle of spermatozoa formation to be completed. However, if a gross spermatozoa deficiency (azoospermia or severe oligozoospermia) has been detected, the repeat test should be undertaken as soon as possible.
Assessing ovulation
B - Women who are concerned about their fertility should be asked about the frequency and regularity of their menstrual cycles. Women with regular monthly menstrual cycles should be informed that they are likely to be ovulating.
B - Women with regular menstrual cycles and more than 1 year's infertility can be offered a blood test to measure serum progesterone in the midluteal phase of their cycle (day 21 of a 28-day cycle) to confirm ovulation.
GPP - Women with prolonged irregular menstrual cycles should be offered a blood test to measure serum progesterone. Depending on the timing of menstrual periods, this test may need to be conducted later in the cycle (for example day 28 of a 35-day cycle) and repeated weekly thereafter until the next menstrual cycle starts.
B - The use of basal body temperature charts to confirm ovulation does not reliably predict ovulation and is not recommended.
GPP - Women with irregular menstrual cycles should be offered a blood test to measure serum gonadotrophins (follicle-stimulating hormone and luteinising hormone).
C - Women who are concerned about their fertility should not be offered a blood test to measure prolactin. This test should only be offered to women who have an ovulatory disorder, galactorrhoea, or a pituitary tumour.
C - Tests of ovarian reserve currently have limited sensitivity and specificity in predicting fertility. However, women who have high levels of gonadotrophins should be informed that they are likely to have reduced fertility.
C - Women should be informed that the value of assessing ovarian reserve using Inhibin B is uncertain and is therefore not recommended.
C - Women with possible fertility problems are no more likely than the general population to have thyroid disease and the routine measurement of thyroid function should not be offered. Estimation of thyroid function should be confined to women with symptoms of thyroid disease.
B - Women should not be offered an endometrial biopsy to evaluate the luteal phase as part of the investigation of fertility problems because there is no evidence that medical treatment of luteal phase defect improves pregnancy rates.
Screening for Chlamydia trachomatis
B - Before undergoing uterine instrumentation, women should be offered screening for Chlamydia trachomatis using an appropriately sensitive technique.
C - If the result of a test for Chlamydia trachomatis is positive, women and their sexual partners should be referred for appropriate management with treatment and contact tracing.
GPP - Prophylactic antibiotics should be considered before uterine instrumentation if screening has not been carried out.
Assessing tubal damage
B - Women who are not known to have comorbidities (such as pelvic inflammatory disease, previous ectopic pregnancy, or endometriosis) should be offered hysterosalpingography (HSG) to screen for tubal occlusion because this is a reliable test for ruling out tubal occlusion, and it is less invasive and makes more efficient use of resources than laparoscopy.
A - 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 comorbidities.
B - Women who are thought to have comorbidities should be offered laparoscopy and dye so that tubal and other pelvic pathology can be assessed at the same time.
Assessing uterine abnormalities
B - Women should not be offered hysteroscopy on its own as part of the initial investigation unless clinically indicated because the effectiveness of surgical treatment of uterine abnormalities on improving pregnancy rates has not been established.
Postcoital testing of cervical mucus
A - The routine use of postcoital 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
Medical management
B - Men with hypogonadotropic hypogonadism should be offered gonadotrophin drugs, because these are effective in improving fertility.
A - Men with idiopathic semen abnormalities should not be offered antioestrogens, gonadotrophins, androgens, bromocriptine, or kinin-enhancing drugs, because they have not been shown to be effective.
A - Men should be informed that the significance of antisperm antibodies is unclear and the effectiveness of systemic corticosteroids is uncertain.
A - 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.
Surgical management
C - Where appropriate expertise is available, men with obstructive azoospermia should be offered surgical correction of epididymal blockage because it is likely to restore patency of the duct and improve fertility. Surgical correction should be considered as an alternative to surgical sperm recovery and in vitro fertilisation.
A - Men should not be offered surgery for varicoceles as a form of fertility treatment because it does not improve pregnancy rates.
Management of ejaculatory failure
C - Treatment of ejaculatory failure can restore fertility without the need for invasive methods of sperm retrieval or the use of assisted reproduction procedures. However, further evaluation of different treatment options is needed.
Ovulation Induction
Antioestrogens
A - Women with World Health Organization Group II ovulation disorders (hypothalamic pituitary dysfunction) such as polycystic ovary syndrome should be offered treatment with clomiphene citrate (or tamoxifen) as the first line of treatment for up to 12 months because it is likely to induce ovulation.
B - Women should be informed of the risk of multiple pregnancies associated with both clomiphene citrate and tamoxifen.
A – Women with unexplained fertility problems should be informed that clomiphene citrate treatment increases the chance of pregnancy, but that this needs to be balanced by the possible risks of treatment, especially multiple pregnancy.
GPP - Women undergoing treatment with clomiphene citrate should be offered ultrasound monitoring during at least the first cycle of treatment to ensure that they receive a dose that minimises the risk of multiple pregnancy.
Metformin
A - Anovulatory women with polycystic ovary syndrome who have not responded to clomiphene citrate and who have a body mass index of more than 25 should be offered metformin combined with clomiphene citrate because this increases ovulation and pregnancy rates.
GPP - Women prescribed metformin should be informed of the side effects associated with its use (such as nausea, vomiting, and other gastrointestinal disturbances).
*Note: Metformin is not currently licensed for the treatment of ovulatory disorders in the United Kingdom.
Ovarian drilling
A - Women with polycystic ovary syndrome who have not responded to clomiphene 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.
Gonadotrophin use in ovulation induction therapy for ovulatory disorders
A - Women with World Health Organization Group II ovulation disorders such as polycystic ovary syndrome who do not ovulate with clomiphene 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.
A - Women with World Health Organization Group II ovulation disorders such as polycystic ovary syndrome who ovulate with clomiphene citrate but have not become pregnant after 6 months of treatment should be offered clomiphene citrate-stimulated intrauterine insemination.
Gonadotrophin use during in vitro fertilisation treatment
A - Human menopausal gonadotrophin, urinary follicle-stimulating 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.
Gonadotrophin-releasing hormone analogues in ovulation induction therapy
A - 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.
Gonadotrophin-releasing hormone analogues during in vitro fertilisation treatment
A - 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.
A - The use of gonadotrophin-releasing hormone antagonists is associated with reduced pregnancy rates and is therefore not recommended outside a research context.
Growth hormone as an adjunct to ovulation induction therapy
A – 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 clomiphene citrate is not recommended because it does not improve pregnancy rates.
Pulsatile gonadotrophin-releasing hormone
B – Women with World Health Organization Group I ovulation disorders (hypothalamic pituitary failure, characterized by hypothalamic amenorrhoea or hypogonadotropic hypogonadism) should be offered pulsatile administration of gonadotrophin-releasing hormone or gonadotrophins with luteinising hormone activity because these are effective in inducing ovulation.
A – The effectiveness of pulsatile gonadotrophin-releasing hormone in women with clomiphene citrate-resistant polycystic ovary syndrome is uncertain and is therefore not recommended outside a research context.
Dopamine agonists
A – 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.
Monitoring ovulation induction during gonadotrophin therapy
C – Women who are offered ovulation induction with gonadotrophins should be informed about the risk of multiple pregnancy and ovarian hyperstimulation before starting treatment.
C – Ovarian ultrasound monitoring to measure follicular size and number should be an integral part of patient management during gonadotrophin therapy to reduce the risk of multiple pregnancy and ovarian hyperstimulation.
Other risks and side effects associated with ovulation induction agents
C – Women who are offered ovulation induction should be informed that a possible association between ovulation induction therapy and ovarian cancer remains uncertain. Practitioners should confine the use of ovulation induction agents to the lowest effective dose and duration of use.
Tubal and Uterine Surgery
Tubal microsurgery and laparoscopic tubal surgery
D – For women with mild tubal disease tubal surgery may be more effective than no treatment. In centres where appropriate expertise is available, it may be considered as a treatment option.
Tubal catheterisation or cannulation
B – For women with proximal tubal obstruction, selective salpingography plus tubal catheterisation, or hysteroscopic tubal cannulation, may be treatment options because these treatments improve the chance of pregnancy.
Uterine surgery
C – Women with amenorrhoea who are found to have intrauterine adhesions should be offered hysteroscopic adhesiolysis because this is likely to restore menstruation and improve the chance of pregnancy.
Medical and Surgical Management of Endometriosis
Medical management (ovarian suppression)
A – Medical treatment of minimal and mild endometriosis does not enhance fertility in subfertile women and should not be offered.
Surgical ablation
A – 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.
A – Women with ovarian endometriomas should be offered laparoscopic cystectomy because this improves the chance of pregnancy.
B – Women with moderate or severe endometriosis should be offered surgical treatment because it improves the chance of pregnancy.
A – Postoperative medical treatment does not improve pregnancy rates in women with moderate to severe endometriosis and is not recommended.
Intrauterine Insemination
A – Couples with mild male factor fertility problems, unexplained fertility problems, or minimal to mild endometriosis should be offered up to six cycles of intrauterine insemination because this increases the chance of pregnancy.
A – Where intrauterine insemination is used to manage male factor fertility problems, ovarian stimulation should not be offered because it is no more clinically effective than unstimulated intrauterine insemination and it carries a risk of multiple pregnancy.
A – Where intrauterine insemination is used to manage unexplained fertility problems, both stimulated and unstimulated intrauterine 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 intrauterine insemination, because it carries a risk of multiple pregnancy.
A – Where intrauterine 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 intrauterine insemination is uncertain.
A – Where intrauterine insemination is undertaken, single rather than double insemination should be offered.
A – Where intrauterine 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
Surgery for hydrosalpinges before in vitro fertilisation treatment
A – Women with hydrosalpinges should be offered salpingectomy, preferably by laparoscopy, before in vitro fertilisation treatment because this improves the chance of a live birth.
Female age
C – Women should be informed that the chance of a live birth following in vitro fertilisation treatment varies with female age and that the optimal female age range for in vitro fertilisation treatment is 23–39 years. Chances of a live birth per treatment cycle are:
- greater than 20% for women aged 23–35 years
- 15% for women aged 36–38 years
- 10% for women aged 39 years
- 6% for women aged 40 years or older.
The effectiveness of in vitro fertilisation treatment in women younger than 23 years is uncertain because very few women in this age range have in vitro fertilisation treatment.
Number of embryos to be transferred and multiple pregnancy
C – Couples should be informed that the chance of multiple pregnancy following in vitro fertilisation treatment depends on the number of embryos transferred per cycle of treatment. To balance the chance of a live birth and the risk of multiple pregnancy and its consequences, no more than two embryos should be transferred during any one cycle of in vitro fertilisation treatment.
Number of previous treatment cycles
C – Couples should be informed that the chance of a live birth following in vitro fertilisation treatment is consistent for the first three cycles of treatment, but that the effectiveness after three cycles is less certain.
Pregnancy history
C – Women should be informed that in vitro fertilization treatment is more effective in women who have previously been pregnant and/or had a live birth.
Alcohol, smoking and caffeine consumption
C – Couples should be informed that the consumption of more than one unit of alcohol per day reduces the effectiveness of assisted reproduction procedures, including in vitro fertilisation treatment.
C – Couples should be informed that maternal and paternal smoking can adversely affect the success rates of assisted reproduction procedures, including in vitro fertilization treatment.
C – Couples should be informed that caffeine consumption has adverse effects on the success rates of assisted reproduction procedures, including in vitro fertilisation treatment.
Body weight
B – Women should be informed that female body mass index should ideally be in the range 19–30 before commencing assisted reproduction, and that a female body mass index outside this range is likely to reduce the success of assisted reproduction procedures.
Clinical effectiveness and referral for in vitro fertilisation treatment
GPP - Couples in which the woman is aged 23–39 years at the time of treatment and who have an identified cause for their fertility problems (such as azoospermia or bilateral tubal occlusion) or who have infertility of at least 3 years’ duration should be offered up to three stimulated cycles of in vitro fertilisation treatment.
GPP - Embryos not transferred during a stimulated in vitro fertilisation treatment cycle may be suitable for freezing. If two or more embryos are frozen, then they should be transferred before the next stimulated treatment cycle because this will minimise ovulation induction and egg collection, both of which carry risks for the woman and use more resources.
Gamete intrafallopian transfer and zygote intrafallopian transfer
A – 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
Medical assessment and screening
B - People undergoing in vitro fertilisation treatment should be offered screening for HIV, hepatitis B virus, and hepatitis C virus; people found to test positive should be managed and counselled appropriately.
Management of couples with viral infections
D - In considering the decision to provide fertility treatment for couples with HIV, hepatitis B, or hepatitis C infections, the implications of these infections for potential children should be taken into account.
Ovulation induction during in vitro fertilisation treatment
A - Natural cycle in vitro fertilisation has lower pregnancy rates per cycle of treatment than clomiphene citrate-stimulated and gonadotrophin-stimulated in vitro fertilisation and is therefore not recommended, except in the rare circumstances where gonadotrophin use is contraindicated.
B - For women who have regular ovulatory cycles, the likelihood of a live birth after replacement of frozen-thawed embryos is similar whether the embryos are replaced during natural or stimulated cycles.
A - The use of adjuvant growth hormone with gonadotrophins during in vitro fertilisation cycles does not improve pregnancy rates and is therefore not recommended.
Oocyte maturation – human chorionic gonadotrophin
A - 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 of stimulated cycles
C - Ultrasound monitoring of ovarian response should form an integral part of the in vitro fertilisation treatment cycle.
A - 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.
Ovarian hyperstimulation syndrome
GPP - Clinics providing ovarian stimulation with gonadotrophins should have protocols in place for preventing, diagnosing, and managing ovarian hyperstimulation syndrome.
A - Women who have a significant risk of developing ovarian hyperstimulation syndrome should not be offered oocyte maturation (or luteal support) using human chorionic gonadotrophin.
Oocyte retrieval
A - Women undergoing transvaginal retrieval of oocytes should be offered conscious sedation because it is a safe and acceptable method of providing analgesia.
D - The safe practice of administering sedative drugs published by the Academy of Medical Royal Colleges should be followed.
A - 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
A - Assisted hatching is not recommended because it has not been shown to improve pregnancy rates.
Embryo transfer techniques
A - Women undergoing in vitro fertilisation treatment should be offered ultrasound-guided embryo transfer because this improves pregnancy rates.
B - Embryo transfers on day 2 or 3 and day 5 or 6 appear to be equally effective in terms of increased pregnancy and live birth rates per cycle started.
B - Replacement of embryos into a uterine cavity with an endometrium of less than 5 mm thickness is unlikely to result in a pregnancy and is therefore not recommended.
A - 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.
Luteal support
A - Women who are undergoing in vitro fertilization 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.
A - 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
Indications for intracytoplasmic sperm injection
B - The recognised indications for treatment by intracytoplasmic sperm injection include:
- Severe deficits in semen quality
- Obstructive azoospermia
- Non-obstructive azoospermia.
In addition, treatment by intracytoplasmic sperm injection should be considered for couples in whom a previous in vitro fertilisation treatment cycle has resulted in failed or very poor fertilisation.
Genetic issues and counselling
C - Before considering treatment by intracytoplasmic sperm injection, couples should undergo appropriate investigations, both to establish a diagnosis and to enable informed discussion about the implications of treatment.
B - Before treatment by intracytoplasmic sperm injection, consideration should be given to relevant genetic issues.
B - Where a specific genetic defect associated with male infertility is known or suspected, couples should be offered appropriate genetic counselling and testing.
B - Where the indication for intracytoplasmic sperm injection is a severe deficit of semen quality or non-obstructive azoospermia, the man's karyotype should be established.
GPP - Men who are undergoing karyotype testing should be offered genetic counselling regarding the genetic abnormalities that may be detected.
C - Testing for Y chromosome microdeletions should not be regarded as a routine investigation before intracytoplasmic sperm injection. However, it is likely that a significant proportion of male infertility results from abnormalities of genes on the Y chromosome involved in the regulation of spermatogenesis, and couples should be informed of this.
Intracytoplasmic sperm injection versus in vitro fertilisation
A - 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.
Sperm recovery
C - Surgical sperm recovery before intracytoplasmic sperm injection may be performed using several different techniques depending on the pathology and wishes of the patient. In all cases, facilities for cryopreservation of spermatozoa should be available.
Donor Insemination
Indications for donor insemination
B - The use of donor insemination is considered effective in managing fertility problems associated with the following conditions:
- Obstructive azoospermia
- Non-obstructive azoospermia
- Infectious disease in the male partner (such as HIV)
- Severe rhesus isoimmunisation
- Severe deficits in semen quality in couples who do not wish to undergo intracytoplasmic sperm injection
Donor insemination should also be considered in certain cases where there is a high risk of transmitting a genetic disorder to the offspring.
Information and counselling
C - Couples should be offered information about the relative merits of intracytoplasmic sperm injection and donor insemination in a context that allows equal access to both treatment options.
C - Couples considering donor insemination should be offered counselling from someone who is independent of the treatment unit regarding all the physical and psychological implications of treatment for themselves and potential children.
Screening of sperm donors
C - Units undertaking semen donor recruitment and the cryopreservation of donor spermatozoa for treatment purposes should follow the current guidelines issued by the British Andrology Society describing the selection and screening of donors.
GPP - All potential semen donors should be offered counseling from someone who is independent of the treatment unit regarding the implications for themselves and their genetic children, including any potential children resulting from donated semen.
Assessment of female partner
C - Before starting treatment by donor insemination it is important to confirm that the woman is ovulating. Women with a history that is suggestive of tubal damage should be offered tubal assessment before treatment.
GPP - Women with no risk factors in their history should be offered tubal assessment after three cycles if treatment has been unsuccessful.
Intrauterine insemination versus intracervical insemination
A - Couples using donor sperm should be offered intrauterine insemination in preference to intracervical insemination because it improves pregnancy rates.
Unstimulated versus stimulated donor insemination
GPP - Women who are ovulating regularly should be offered a minimum of six cycles of donor insemination without ovarian stimulation to reduce the risk of multiple pregnancy and its consequences.
Timing of donor insemination
C - Couples should be informed that timing of insemination using either urinary luteinising hormone or basal body temperature changes is equally effective in donor cycles. However, using urinary luteinising hormone detection reduces the number of clinic visits per cycle.
Maximum number of cycles
GPP - Couples should be offered other treatment options after six unsuccessful cycles of donor insemination.
Oocyte Donation
Indications for oocyte donation
C - The use of donor oocytes is considered effective in managing fertility problems associated with the following conditions:
- Premature ovarian failure
- Gonadal dysgenesis including Turner syndrome
- Bilateral oophorectomy
- Ovarian failure following chemotherapy or radiotherapy
- Certain cases of in vitro fertilisation treatment failure.
Oocyte donation should also be considered in certain cases where there is a high risk of transmitting a genetic disorder to the offspring.
Screening of oocyte donors
D - Before donation is undertaken, oocyte donors should be screened for both infectious and genetic diseases in accordance with guidance issued by the Human Fertilisation and Embryology Authority.
Oocyte donation and egg sharing
C - Oocyte donors should be offered information regarding the potential risks of ovarian stimulation and oocyte collection. The section above titled "Other risks and side effects associated with ovulation induction agents" refers to risks and side effects associated with ovarian stimulation.
GPP - Oocyte recipients and donors should be offered counselling from someone who is independent of the treatment unit regarding the physical and psychological implications of treatment for themselves and their genetic children, including any potential children resulting from donated oocytes.
GPP - All people considering participation in an egg-sharing scheme should be counselled about its particular implications.
Applications of Cryopreservation in Cancer Treatment
D - Before commencing chemotherapy or radiotherapy likely to affect fertility, or management of post-treatment fertility problems, the procedures recommended by the Royal College of Physicians and the Royal College of Radiologists should be followed.
B - Men and adolescent boys preparing for medical treatment that is likely to make them infertile should be offered semen cryostorage because the effectiveness of this procedure has been established.
C - Local protocols should exist to ensure that health professionals are aware of the value of semen cryostorage in these circumstances, so that they deal with the situation sensitively and effectively.
C - Women preparing for medical treatment that is likely to make them infertile should be offered oocyte or embryo cryostorage as appropriate if they are well enough to undergo ovarian stimulation and egg collection, provided that this will not worsen their condition and that sufficient time is available.
D - Women preparing for medical treatment that is likely to make them infertile should be informed that oocyte cryostorage has very limited success, and that cryopreservation of ovarian tissue is still in an early stage of development.
GPP - People preparing for medical treatment that is likely to make them infertile should be offered counselling from someone who is independent of the treatment unit to help them cope with the stress and the potential physical and psychological implications for themselves, their partners, and any potential children resulting from cryostorage of gametes and/or embryos.
GPP - Where cryostorage of gametes and/or embryos is to be undertaken because of medical treatment that is likely to make people infertile, this should occur before such treatment begins.
Follow-up of Children Born as a Result of Assisted Reproduction
C - Couples contemplating assisted reproduction should be given up-to-date information about the health of children born as a result of assisted reproduction. Current research is broadly reassuring about the health and welfare of children born as a result of assisted reproduction.
Definitions
Evidence Categories
1a: Evidence obtained from systematic review and meta-analysis of randomised controlled trials
1b: Evidence obtained from at least one randomised controlled trial
2a: Evidence obtained from at least one well-designed controlled study without randomisation
2b: Evidence obtained from at least one other type of well-designed quasi-experimental study.
3: Evidence obtained from well-designed nonexperimental descriptive studies, such as comparative studies, correlation studies, or case studies
4: Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
Grading of Recommendations
A: Directly based on level 1 evidence
B: Directly based on level 2 evidence, or extrapolated recommendation from level 1 evidence
C: Directly based on level 3 evidence, or extrapolated recommendation from either level 1 or level 2 evidence
D: Directly based on level 4 evidence, or extrapolated recommendation from either level 1, 2, or 3 evidence
Good practice point (GPP): The view of the Guideline Development Group
