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What to do when a couple has problems conceiving
CONCEPTION PROBLEMS
What to do when a couple has problems conceiving
Pre-pregnancy steps General medical history and current health • Pregnancy history of both partners • Weight/BMI • General and abdominal examination where relevant • Blood pressure • Rubella status Advice • Weight and diet • Current medication • Social activity – including alcohol, drugs, smoking, exercise • Role of folate and dosage • Risks from infection, medications and food to avoid • Age-related risks and role of investigation
Julian Jenkins Gill Jenkins
What should you do when a couple first presents to discuss problems conceiving? Around one in four couples present to their GP to discuss infertility1, and the majority of them will ultimately have a child. It is therefore appropriate to take a positive approach, and to see this first consultation as an opportunity to discuss pre-pregnancy care. This maximises the couple’s chances of having a healthy baby and provides an opportunity to assess factors which might affect their fertility (see Table 1).
Table 1
Initial assessment by GP Couple • Duration of infertility, frequency of intercourse, any coital problems
How do you make an initial assessment of whether a couple has an infertility problem? The simplest measure of whether there may be a problem is the duration of trying for a pregnancy – along with the age of the couple, particularly the woman. Most fertility centres have a protocol based on this and will not see a couple until they have been trying for at least 12 to 24 months, although there may be exceptions – for instance, the older woman whose chances will be diminished. A comprehensive GP assessment prior to referral to hospital (see Table 2) will help secondary care formulate a treatment plan.
Male • History: • Age • General history, including previous children from this or other relationship • Examination: genitalia – for example, for scrotal lumps, testicular size • Semen analysis – if abnormal, repeat and refer for advice as appropriate • Fertility centres may ask for hepatitis B, hepatitis C and HIV status (requirement by Human Fertilisation and Embryology Authority if couples proceed to assisted reproduction and wish to store embryos and gametes)
How should you respond to common questions – say, on use of ovulation predictors and referral? Patients should be advised about the statistical chances of conceiving – that, in a cohort, roughly half will become pregnant within six months, 84% within a year and 92% within two years. GPs should be aware of their local unit’s referral policy: most centres require that a couple has been trying to conceive for at least 12 months, unless there is an indication for earlier referral. Many patients will ask about ovulation predictors and self-test kits. The exact value of ovulation prediction kits that detect the surge of luteinising hormone (LH) is unclear, and reflects the complexity of ovarian function and other factors related to fertility – they are reliable but of very little use to aid conception, and can cause unnecessary anxiety. More recently, self-test kits for male
Female • History: • Age • General history – illnesses, medication, social • Gynaecological history – menarche, menstrual history, pregnancies, infections, operations (gynaecological or other) • Examination – weight , BMI, thyroid, abdominal check, PV • Tests – most centres ask for FSH/LH, FBC, progesterone (five to ten days before period due), rubella, possibly chlamydia serology and, if menses not regular, TFTs and prolactin. Also possibly hepatitis B, hepatitis C and HIV, as above Table 2
Julian Jenkins is a consultant senior lecturer at the Centre for Reproductive Medicine, University of Bristol.
and female fertility have been marketed. The male test provided in the Fertell kit indicates whether there is an adequate number of active sperm in a semen sample. If positive, this can be reassuring, but if negative, the man would require a formal semen analysis.
Gill Jenkins is a GP at Whiteladies Health Centre, Bristol. This article has been reproduced from: Doctor, 14th March 2006: 36.
WOMEN’S HEALTH MEDICINE 3:6
241
© 2006 Elsevier Ltd
CONCEPTION PROBLEMS
What are the current national guidelines on referral to hospital?
Which treatment for which problem?
In February 2004, NICE published comprehensive guidelines on infertility management for the NHS in Wales and England.2 The guidelines stated that up to three full cycles of IVF should be made available on the NHS to all those couples meeting agreed clinical criteria. The then health secretary, John Reid, asked PCTs to make available at least one full cycle of IVF by April 2005, with preference to be given to those without children. Unfortunately, a recent survey co-ordinated by the National Infertility Awareness Campaign revealed that these guidelines were not yet being followed.3
Over the last few decades, there have been remarkable advances in infertility treatment, so the overwhelming majority of couples can be helped. It is important to confirm that the couple has regular intercourse and to address any sexual dysfunction. In many cases, reassurance and support may allow couples to conceive spontaneously, or basic infertility treatment will suffice (see Table 3). Assisted reproduction technologies (ART) provide a broad range of treatments, addressing even the most serious infertility problem (see Table 4).
ART options and indications Assisted reproduction technologies Indications
Basic infertility treatments Problem Male factor
Ovulatory
In-vitro fertilisation Tubal infertility; unexplained infertility; where other treatments, such as ovulation induction and donor insemination, have been unsuccessful
Initial infertility treatment options Mild male factor problems are sometimes treated with intrauterine insemination (IUI), although the place for IUI is controversial, particularly whether it should be combined with ovarian stimulation Rarely, men may have hypothalamic pituitary failure, which can be treated with gonadotrophins
Intracytoplasmic sperm injection (ICSI) – a procedure in which a single sperm is injected into the egg to enable fertilisation with very low sperm counts or other problems such as low motility Male factor problems – for example, low sperm count, low sperm motility, high percentage abnormal sperm morphology or significant anti-sperm antibodies; previous poor or failed fertilisation with IVF
If obese or underweight, aim to normalise weight Clomifene and tamoxifen may stimulate the ovaries through an increase in the body’s own follicle-stimulating hormone production Metformin may counteract adverse effects on the ovary of hyperinsulaemia in polycystic ovary syndrome Controlled injury may restore spontaneous ovulation in patients with polycystic ovary syndrome Bromocriptine may reduce hyperprolactinaemia, restoring normal ovulation Gonadotrophin-releasing hormone pump may correct hypothalamic pituitary failure Gonadotrophin therapy may be used if the above are unsuccessful
Tubal
Surgery may be appropriate for mild tubal disease (ART if more severe) Transcervical tubal catheterisation can treat proximal occlusion
Endometriosis Unexplained
Laparoscopic or open surgery may be appropriate Clomifene may be used, although this has only marginal influence on improving fertility IUI may be used, although there is disagreement regarding efficacy and whether it should be combined with ovarian stimulation
Surgical sperm recovery – collection of sperm by various surgical methods when no sperm is present in the ejaculate. Usually combined with ICSI as resultant sperm numbers are low Obstructive azoospermia – failed vasectomy reversal, cystic fibrosis; testicular failure Donor insemination For patients who choose not to have ICSI when there is a major sperm problem; where it is not possible to obtain viable sperm even following surgical sperm retrieval; genetic disorder Donor eggs – eggs are donated by one woman for the treatment of another using IVF Premature ovarian failure; risk of transmitting genetic disorders; gonadal dysgenesis; oophorectomy; ovarian failure after chemotherapy or radiotherapy; selected cases of IVF treatment failures (for example, poor response) Gamete intrafallopian tube transfer (GIFT) – eggs are collected from ovaries then placed in fallopian tubes with prepared sperm at laparoscopy This treatment is used for unexplained infertility, particularly when IVF was unavailable; with the increasing availability and success of IVF, there is now little place for GIFT
For further information, see Jenkins et al 20024
Modified with permission from Jenkins et al 20055 Table 4
Table 3
WOMEN’S HEALTH MEDICINE 3:6
242
© 2006 Elsevier Ltd
CONCEPTION PROBLEMS
What are the treatment complications that you should be aware of?
Where can GPs find more data on infertility? The references below provide more useful information for GPs. For the latest infertility news you can visit the website of the British Fertility Society at www.fertility.org.uk.
Although GPs should not be prescribing gonadotrophin treatment, those with a specialist interest in infertility may enter into a sharedcare agreement with hospital practitioners for oral treatments for ovulatory problems. Local guidelines on any such agreement should include side-effects of treatment, such as the risk of lactic acidosis with metformin, and the policy regarding ovarian monitoring to reduce the risk of multiple pregnancy with clomifene. Fortunately, most infertility treatments are well tolerated by patients. The most significant complication is the increased risk of multiple pregnancy with ART. In part, this is a social issue, as the UK has a very poor provision of state-funded ART compared to other European countries. State-funded patients tend to accept the transfer of a single embryo, whereas self-funded patients in the UK are more likely to request two embryos to be transferred to increase their chances of pregnancy. Of the various side-effects from the drugs used in ART, the most important is ovarian hyperstimulation syndrome: following ovarian stimulation, the ovaries become enlarged, painful and cause complications that result in nausea, vomiting and potentially serious systemic effects such as thromboembolic disease. With increasing numbers of patients undergoing ART, GPs should be aware of the risks and symptoms of ovarian hyperstimulation syndrome. And if a GP suspects this problem, it should be discussed urgently with a specialist.
WOMEN’S HEALTH MEDICINE 3:6
REFERENCES 1 Gunnell DJ, Ewings P. Infertility prevalence, needs assessment and purchasing. Journal of Public Health Medicine 1994; 16: 29–36. 2 NICE. Clinical guidelines on fertility. www.nice.org.uk/page. aspx?o=104435. 3 All Party Parliamentary Group on Infertility. PCT survey shows some progress, but inequalities still exist. 2005. www. fertilityfriends.co.uk/content/view/275/1/ 4 Jenkins JM, Corrigan L, Chambers R. Infertility Matters In Healthcare. Oxford: Radcliffe Medical Press, 2002. ISBN: 1 85775 960 5 5 Jenkins J, Keay S, Wakley G, Chambers R. Demonstrating Your Competence 6: Reproductive Health – A Guide for Hospital Doctors, their Trainers and Practitioners with a Special Interest. Oxford: Radcliffe Publishing, 2005. ISBN 1 85775 620 7
243
© 2006 Elsevier Ltd
What to do when a couple has problems conceiving
Pre-pregnancy steps General medical history and current health • Pregnancy history of both partners • Weight/BMI • General and abdominal examination where relevant • Blood pressure • Rubella status Advice • Weight and diet • Current medication • Social activity – including alcohol, drugs, smoking, exercise • Role of folate and dosage • Risks from infection, medications and food to avoid • Age-related risks and role of investigation
Julian Jenkins Gill Jenkins
What should you do when a couple first presents to discuss problems conceiving? Around one in four couples present to their GP to discuss infertility1, and the majority of them will ultimately have a child. It is therefore appropriate to take a positive approach, and to see this first consultation as an opportunity to discuss pre-pregnancy care. This maximises the couple’s chances of having a healthy baby and provides an opportunity to assess factors which might affect their fertility (see Table 1).
Table 1
Initial assessment by GP Couple • Duration of infertility, frequency of intercourse, any coital problems
How do you make an initial assessment of whether a couple has an infertility problem? The simplest measure of whether there may be a problem is the duration of trying for a pregnancy – along with the age of the couple, particularly the woman. Most fertility centres have a protocol based on this and will not see a couple until they have been trying for at least 12 to 24 months, although there may be exceptions – for instance, the older woman whose chances will be diminished. A comprehensive GP assessment prior to referral to hospital (see Table 2) will help secondary care formulate a treatment plan.
Male • History: • Age • General history, including previous children from this or other relationship • Examination: genitalia – for example, for scrotal lumps, testicular size • Semen analysis – if abnormal, repeat and refer for advice as appropriate • Fertility centres may ask for hepatitis B, hepatitis C and HIV status (requirement by Human Fertilisation and Embryology Authority if couples proceed to assisted reproduction and wish to store embryos and gametes)
How should you respond to common questions – say, on use of ovulation predictors and referral? Patients should be advised about the statistical chances of conceiving – that, in a cohort, roughly half will become pregnant within six months, 84% within a year and 92% within two years. GPs should be aware of their local unit’s referral policy: most centres require that a couple has been trying to conceive for at least 12 months, unless there is an indication for earlier referral. Many patients will ask about ovulation predictors and self-test kits. The exact value of ovulation prediction kits that detect the surge of luteinising hormone (LH) is unclear, and reflects the complexity of ovarian function and other factors related to fertility – they are reliable but of very little use to aid conception, and can cause unnecessary anxiety. More recently, self-test kits for male
Female • History: • Age • General history – illnesses, medication, social • Gynaecological history – menarche, menstrual history, pregnancies, infections, operations (gynaecological or other) • Examination – weight , BMI, thyroid, abdominal check, PV • Tests – most centres ask for FSH/LH, FBC, progesterone (five to ten days before period due), rubella, possibly chlamydia serology and, if menses not regular, TFTs and prolactin. Also possibly hepatitis B, hepatitis C and HIV, as above Table 2
Julian Jenkins is a consultant senior lecturer at the Centre for Reproductive Medicine, University of Bristol.
and female fertility have been marketed. The male test provided in the Fertell kit indicates whether there is an adequate number of active sperm in a semen sample. If positive, this can be reassuring, but if negative, the man would require a formal semen analysis.
Gill Jenkins is a GP at Whiteladies Health Centre, Bristol. This article has been reproduced from: Doctor, 14th March 2006: 36.
WOMEN’S HEALTH MEDICINE 3:6
241
© 2006 Elsevier Ltd
CONCEPTION PROBLEMS
What are the current national guidelines on referral to hospital?
Which treatment for which problem?
In February 2004, NICE published comprehensive guidelines on infertility management for the NHS in Wales and England.2 The guidelines stated that up to three full cycles of IVF should be made available on the NHS to all those couples meeting agreed clinical criteria. The then health secretary, John Reid, asked PCTs to make available at least one full cycle of IVF by April 2005, with preference to be given to those without children. Unfortunately, a recent survey co-ordinated by the National Infertility Awareness Campaign revealed that these guidelines were not yet being followed.3
Over the last few decades, there have been remarkable advances in infertility treatment, so the overwhelming majority of couples can be helped. It is important to confirm that the couple has regular intercourse and to address any sexual dysfunction. In many cases, reassurance and support may allow couples to conceive spontaneously, or basic infertility treatment will suffice (see Table 3). Assisted reproduction technologies (ART) provide a broad range of treatments, addressing even the most serious infertility problem (see Table 4).
ART options and indications Assisted reproduction technologies Indications
Basic infertility treatments Problem Male factor
Ovulatory
In-vitro fertilisation Tubal infertility; unexplained infertility; where other treatments, such as ovulation induction and donor insemination, have been unsuccessful
Initial infertility treatment options Mild male factor problems are sometimes treated with intrauterine insemination (IUI), although the place for IUI is controversial, particularly whether it should be combined with ovarian stimulation Rarely, men may have hypothalamic pituitary failure, which can be treated with gonadotrophins
Intracytoplasmic sperm injection (ICSI) – a procedure in which a single sperm is injected into the egg to enable fertilisation with very low sperm counts or other problems such as low motility Male factor problems – for example, low sperm count, low sperm motility, high percentage abnormal sperm morphology or significant anti-sperm antibodies; previous poor or failed fertilisation with IVF
If obese or underweight, aim to normalise weight Clomifene and tamoxifen may stimulate the ovaries through an increase in the body’s own follicle-stimulating hormone production Metformin may counteract adverse effects on the ovary of hyperinsulaemia in polycystic ovary syndrome Controlled injury may restore spontaneous ovulation in patients with polycystic ovary syndrome Bromocriptine may reduce hyperprolactinaemia, restoring normal ovulation Gonadotrophin-releasing hormone pump may correct hypothalamic pituitary failure Gonadotrophin therapy may be used if the above are unsuccessful
Tubal
Surgery may be appropriate for mild tubal disease (ART if more severe) Transcervical tubal catheterisation can treat proximal occlusion
Endometriosis Unexplained
Laparoscopic or open surgery may be appropriate Clomifene may be used, although this has only marginal influence on improving fertility IUI may be used, although there is disagreement regarding efficacy and whether it should be combined with ovarian stimulation
Surgical sperm recovery – collection of sperm by various surgical methods when no sperm is present in the ejaculate. Usually combined with ICSI as resultant sperm numbers are low Obstructive azoospermia – failed vasectomy reversal, cystic fibrosis; testicular failure Donor insemination For patients who choose not to have ICSI when there is a major sperm problem; where it is not possible to obtain viable sperm even following surgical sperm retrieval; genetic disorder Donor eggs – eggs are donated by one woman for the treatment of another using IVF Premature ovarian failure; risk of transmitting genetic disorders; gonadal dysgenesis; oophorectomy; ovarian failure after chemotherapy or radiotherapy; selected cases of IVF treatment failures (for example, poor response) Gamete intrafallopian tube transfer (GIFT) – eggs are collected from ovaries then placed in fallopian tubes with prepared sperm at laparoscopy This treatment is used for unexplained infertility, particularly when IVF was unavailable; with the increasing availability and success of IVF, there is now little place for GIFT
For further information, see Jenkins et al 20024
Modified with permission from Jenkins et al 20055 Table 4
Table 3
WOMEN’S HEALTH MEDICINE 3:6
242
© 2006 Elsevier Ltd
CONCEPTION PROBLEMS
What are the treatment complications that you should be aware of?
Where can GPs find more data on infertility? The references below provide more useful information for GPs. For the latest infertility news you can visit the website of the British Fertility Society at www.fertility.org.uk.
Although GPs should not be prescribing gonadotrophin treatment, those with a specialist interest in infertility may enter into a sharedcare agreement with hospital practitioners for oral treatments for ovulatory problems. Local guidelines on any such agreement should include side-effects of treatment, such as the risk of lactic acidosis with metformin, and the policy regarding ovarian monitoring to reduce the risk of multiple pregnancy with clomifene. Fortunately, most infertility treatments are well tolerated by patients. The most significant complication is the increased risk of multiple pregnancy with ART. In part, this is a social issue, as the UK has a very poor provision of state-funded ART compared to other European countries. State-funded patients tend to accept the transfer of a single embryo, whereas self-funded patients in the UK are more likely to request two embryos to be transferred to increase their chances of pregnancy. Of the various side-effects from the drugs used in ART, the most important is ovarian hyperstimulation syndrome: following ovarian stimulation, the ovaries become enlarged, painful and cause complications that result in nausea, vomiting and potentially serious systemic effects such as thromboembolic disease. With increasing numbers of patients undergoing ART, GPs should be aware of the risks and symptoms of ovarian hyperstimulation syndrome. And if a GP suspects this problem, it should be discussed urgently with a specialist.
WOMEN’S HEALTH MEDICINE 3:6
REFERENCES 1 Gunnell DJ, Ewings P. Infertility prevalence, needs assessment and purchasing. Journal of Public Health Medicine 1994; 16: 29–36. 2 NICE. Clinical guidelines on fertility. www.nice.org.uk/page. aspx?o=104435. 3 All Party Parliamentary Group on Infertility. PCT survey shows some progress, but inequalities still exist. 2005. www. fertilityfriends.co.uk/content/view/275/1/ 4 Jenkins JM, Corrigan L, Chambers R. Infertility Matters In Healthcare. Oxford: Radcliffe Medical Press, 2002. ISBN: 1 85775 960 5 5 Jenkins J, Keay S, Wakley G, Chambers R. Demonstrating Your Competence 6: Reproductive Health – A Guide for Hospital Doctors, their Trainers and Practitioners with a Special Interest. Oxford: Radcliffe Publishing, 2005. ISBN 1 85775 620 7
243
© 2006 Elsevier Ltd