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National Collaborating Centre for Women's and Children's Health (UK). Fertility: Assessment and Treatment for People with Fertility Problems. London (UK): RCOG Press; 2004 Feb. (NICE Clinical Guidelines, No. 11.)

3Initial advice to people concerned about delays in conception

3.1. Natural conception

The process of human reproduction begins with the deposition of spermatozoa, during sexual intercourse, into the vagina. The spermatozoa migrate through the cervix and uterine cavity to the fallopian tubes where they meet the egg and fertilisation takes place. The embryo then travels back down the fallopian tube and enters the uterine cavity where implantation takes place.

This process is complex and reliant upon the chance of satisfactory ovulation and transport of viable sperm and ova in the reproductive tract. It is influenced by endocrine control, timing and frequency of sexual intercourse, and the general health status of the man and the woman. The length of a menstrual cycle varies between 26 days and 36 days. Ovulation usually takes place 12–16 days before the start of the next period. For a woman with a 28-day menstrual cycle (the first day of menstruation being day one), ovulation takes place around day 14. After ovulation, the egg usually lives for up to 24 hours. After ejaculation, sperm can survive for up to seven days in the genital tract and sometimes even longer (see Section 3.2).17

In the general population (which includes people with fertility problems), it is estimated that 84% of women would conceive within one year of regular unprotected sexual intercourse. This rises cumulatively to 92% after two years and 93% after three years.18,19

Fertility may be measured as conception rate per menstrual cycle. This is known as fecundability. Natural female fertility declines with age,20 [Evidence level 3] but reliable data on fecundability rates of specific age groups in fertile populations are limited. The decline with age in rates of conception is seen after 30 years of age and is more marked after age 35 years.21,22 [Evidence level 3] However, this decline at specific ages should be interpreted with caution as it is based on women receiving artificial donor insemination and fecundability is higher in fertile women having sexual intercourse than in fertile women receiving donor insemination.21,23 The effect of age on male fertility is less clear.24 [Evidence level 3]

Another important factor that can influence conception rates in the general population is coital frequency. Statistical estimates suggest that fecundability rises sharply with frequency of intercourse (see Section 3.2). With regular intercourse, 94% and 77% of fertile women aged 35 years and 38 years conceive after three years of trying.22,25 [Evidence level 3]

Psychological stress can affect libido and coital frequency and hence fertility (see Section 4.2).

RECOMMENDATIONS

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%). [D]

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. [C]

3.2. Frequency and timing of sexual intercourse

Daily intercourse results in the highest probability of conception but is not the only factor influencing conception,26 considering the viability of the egg and its short survival time. [Evidence level 3] Ejaculation eight times per week tends to reduce sperm parameters,27–30 but not the fertility potential of the men.27 The best sperm motility has been found in semen emission every three to four days on average.27 [Evidence level 2b] Coitus every two to three days is likely to maximise the overall chance of natural conception, as spermatozoa survive in the female reproductive tract for up to seven days after insemination.17,30 [Evidence level 3]

It has been observed that most pregnancies can be attributed to sexual intercourse during a six-day period ending on the day of ovulation,31,32 with the highest estimated conception rates associated with intercourse two days before ovulation.33 [Evidence level 3]

Six cohort studies that evaluated the use of basal body temperature or urinary luteinising hormone (LH) kits to time intercourse did not report improvement in the chance of natural conception.34–39 [Evidence level 2b] Timed intercourse has been found to be an emotionally stressful intervention in the initial evaluation of infertility.40 [Evidence level 3] However, for the minority of couples who find it difficult to have frequent sexual intercourse, the prediction of ovulation using LH kits can be useful.

RECOMMENDATION

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. [C]

3.3. Alcohol

There is inconsistent evidence about the impact of alcohol intake on female fertility.41–46 [Evidence level 2b] Excessive alcohol consumption is harmful to the fetus.47 The Department of Health (DH) has recommended that women who are pregnant or trying to become pregnant should drink no more than one or two units of alcohol once or twice per week and should avoid episodes of intoxication.48

One cohort study showed that female wine drinkers (up to seven units per week) had slightly shorter waiting times to pregnancy than non-wine drinkers and drinkers of other alcoholic beverages, after adjusting for age, parity, smoking and body mass index (BMI).49 [Evidence level 2b]

Excessive alcohol consumption can be detrimental to semen quality but the effect is reversible and there is no evidence of a causal association between moderate alcohol consumption and poor semen quality.50–53 [Evidence level 2b] The current recommended guidelines on safe drinking limits for men allow three to four units per day.54

RECOMMENDATION

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. [D]

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. [GPP]

Men should be informed that excessive alcohol intake is detrimental to semen quality. [B]

3.4. Smoking

There is a significant association between smoking and reduced fertility among female smokers.55,56 [evidence level 2b] There is an association in men between smoking and reduced semen parameters.51,57–62 [Evidence level 2b] However, the relationship between male smoking habits and fertility is uncertain. Male and female exposure in utero is associated with reduced fertility later in life.63 [Evidence level 2b]

It has been reported that passive smoking in women is associated with delayed conception.64 [Evidence level 2b]

For women with fertility problems, basic information about the impact of smoking on fertility or a scripted three- to five-minute intervention with booklets specific to the woman’s ‘stage-of-change’ smoking continuum, together with exhaled carbon monoxide monitoring, were highly effective in stopping smoking but not in improving pregnancy rates.65 [Evidence level 1b] We found no studies that investigated the effect of the use of nicotine replacement therapy on infertility.

There are significant associations between maternal cigarette smoking in pregnancy and increased risks of small-for-gestational-age infants,66 stillbirth67 and infant mortality.68 [evidence level 2b] For further information please refer to the Antenatal Care Guideline.1147

RECOMMENDATIONS

Women who smoke should be informed that this is likely to reduce their fertility. [B]

Women who smoke should be offered referral to a smoking cessation programme to support their efforts in stopping smoking. [A]

Women should be informed that passive smoking is likely to affect their chance of conceiving. [B]

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. [GPP]

3.5. Caffeinated beverages

Caffeine is present in coffee, tea, colas and chocolate. The association between caffeine and female infertility is inconsistent.45,69–80 [evidence level 2b] We did not find any studies reporting the effect of caffeine on pregnancy rates, nor studies which investigated the effect of decaffeinated beverages on fertility.

We found one study addressing the question of caffeine intake and male fertility. This study showed no evidence of an association between caffeine intake and poor semen parameters. However, the combination of coffee drinking with smoking diminished sperm motility and increased the proportion of dead sperm.51 [evidence level 2b]

RECOMMENDATIONS

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. [B]

3.6. Body weight

Obesity

BMI is a measure of body fat calculated from an individual’s weight and height (kg/m2). The internationally accepted range for BMI is from less than 18.5 kg/m2 (underweight) to 30 kg/m2 or over (obese).81 Women with BMI over 30 kg/m2 take longer to conceive, compared with women with lower BMI, even after adjusting for other factors such as menstrual irregularity.82–84 [evidence level 2b] For infertile anovulatory women with BMI of over 29 kg/m2, there is evidence that a supervised weight loss programme or a group programme including exercise, dietary advice and support helps to reduce weight,85,86 resume ovulation85 and improve pregnancy rates.86 [Evidence level 1b]

A BMI of 30 or over was reported to be an independent risk factor for spontaneous abortion in women who were oocyte recipients.87 [evidence level 3]

An increased risk of miscarriage has been reported in moderately obese women (BMI 25–27.9 kg/m2 ) with polycystic ovary syndrome (PCOS; see Section 5.2) undergoing ovulation induction.88 [Evidence level 2b]

An observational study reported an inverse relationship between BMI and the total number of normal-motile sperm cells. There was a significant reduced number of normal-motile sperm cells in men who were overweight (BMI 25–30) and obese (BMI greater than 30) when compared with men of normal weight (BMI 20–24).89 [evidence level 3] A higher incidence of sperm DNA fragmentation has also been observed in men with a BMI of over 25.90 [evidence level 3]

Obesity may have a deleterious effect on erectile function in men with existing vascular risk factors such as heart disease and diabetes.91 [evidence level 2b]

RECOMMENDATIONS

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. [B]

Women should be informed that participating in a group programme involving exercise and dietary advice leads to more pregnancies than weight loss advice alone. [A]

Men who have a body mass index of more than 29 should be informed that they are likely to have reduced fertility. [C]

Low body weight

Low body weight is recognised as an important cause of hypooestrogenic amenorrhoea. It is important that the subgroup of women who have anorexia nervosa are detected and managed appropriately. Many women with hypooestrogenic amenorrhoea associated with low body weight do not wish to conceive and the management priority for these women will lie outside the scope of this guideline.

In women, weight loss of over 15% of ideal body weight is associated with menstrual dysfunction and secondary amenorrhoea when over 30% of body fat is lost.92 Restoration of body weight may help to resume ovulation and restore fertility.93,94 [Evidence level 2b]

An increased risk of preterm delivery has been associated with women who are underweight, and ovulation induction in such women has been associated with a higher incidence of babies who were small for gestational age.95 [Evidence level 2b]

RECOMMENDATION

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. [B]

3.7. Tight underwear for men

Increased scrotal temperature is closely associated with reduced semen quality in healthy populations.96–98 [Evidence level 3] Important determinants of testicular temperature such as a sedentary work position and occupational heat exposure have been associated with abnormal semen quality (see Section 3.8).98,99 [Evidence level 3] There is some evidence that, in a fertile population, wearing tight-fitting underwear can impair semen quality.100 [Evidence level Ib] However, the effect of impaired semen quality on pregnancy rates has not been established. A cohort study of 97 men with subfertility showed that there was no difference in scrotal temperatures and semen parameters between a group wearing boxer shorts and a group wearing briefs.101 [Evidence level 2b]

RECOMMENDATION

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. [B]

3.8. Occupation

More than 104 000 chemical and physical agents have been identified in the workplace but the effects on reproduction of at least 95% of them have not been assessed, partly because of the fast rate of introduction of these agents into industry.102 Tables 3.1 and 3.2 summarise the main occupational agents implicated in the reduction of human fertility.103–109 [Evidence level 2b–3] The lists of agents presented in the tables is not exhaustive.

Table 3.1. Occupational agents and their effects on male fertility.

Table 3.1

Occupational agents and their effects on male fertility.

Table 3.2. Occupational agents and their effects on female fertility.

Table 3.2

Occupational agents and their effects on female fertility.

Evidence suggestive of a harmful effect on the human reproductive system has been recognised for specific agents, such as heat, X-rays, metals and pesticides, whereas for many other agents the association is only suspected and needs further evaluation.

RECOMMENDATION

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. [B]

3.9. Prescribed, over-the-counter and recreational drug use

A number of prescribed, over-the-counter and recreational drugs may interfere with male or female fertility. However, the potential benefits and risks of certain medications need to be weighed and medical advice sought in order to determine the appropriate course for individual patients.

Prescribed drug use

There is evidence that nonsteroidal anti-inflammatory drugs inhibit ovulation.158,159 [Evidence level 1b] Immunosuppressive and anti-inflammatory drugs for rheumatic diseases may affect conception.160 [evidence level 3] In a case–control study, women who had ever used thyroid replacement hormones, antidepressants, tranquilisers or asthma medication were reported to have elevated risks of anovulatory infertility.161 [Evidence level 2b] Chemotherapy treatment with cytotoxic drugs can induce ovarian failure at different rates for various types of malignancies and treatment regimens.162,163 [Evidence level 2b]

Medication such as cimetidine and sulphasalazine and long term-daily use of some antibiotics and androgen injections can affect semen quality and cause oligozoospermia.164–166 The effect is generally reversible after three months following withdrawal of medication. Use of beta-blockers and psychotropic drugs may lead to impotence.167 Chemotherapy treatment can induce azoospermia, which is permanent in most cases.168 [Evidence level 3]

The effect of anti-psoriatic treatment for arthritis with methotrexate on male infertility is unclear.169 [Evidence level 3]

Recreational drug use

The use of recreational drugs or drugs of abuse such as marijuana and cocaine can adversely affect ovulatory and tubal function.170 The use of drugs such as anabolic steroids and cocaine can adversely affect semen quality.171–173 [evidence level 2b–3] Overall, use of these recreational drugs diminishes the fertility potential of the couple. We did not find any studies that assessed the effect of recreational drug use on pregnancy rates.

RECOMMENDATION

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. [B]

3.10. Complementary therapy

We found four RCTs that evaluated the effects of various substances on semen quality,174,175 ovulation and pregnancy rates.176,177 Three of the RCTs174,176,177 were of poor design with unclear methods of randomisation and clinical heterogeneity. The fourth RCT175 compared oral selenium supplementation with selenium plus vitamins or placebo in a group of subfertile men. This RCT reported an improvement in sperm motility and pregnancy rates in the selenium group compared with the placebo group (11% with selenium versus 0% with placebo).175 [Evidence level 1b]

An increase in pregnancy rates was observed in a preliminary trial assessing the effect of intercessory prayer on patients undergoing IVF treatment. However, there is no biological mechanism to explain such an effect.178

RECOMMENDATION

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. [GPP]

3.11. Folic acid supplementation

A systematic review119 of four RCTs (n = 6425 women) showed that periconceptional folate supplementation reduced the incidence of neural rube defects (anencephaly and spina bifida) in children (RR 0.28, 95% CI 0.13 to 0.58). In all four RCTs, folic acid was taken before conception and up to 6–12 weeks of gestation. The dose assessed ranged from 0.36 to 4 milligrams. Multivitamins alone were not associated with prevention of neural tube defects and did not produce additional preventative effects when given in combination with folate.179 [Evidence level 1a] An Expert Advisory Group to the DH recommended a dose of 0.4 milligrams of folic acid per day for women who have not had a previous infant with a neural tube defect and a dose of 5.0 milligrams per day for women who have previously had an infant with a neural tube defect and those who are receiving antiepileptic drugs. Supplementation should continue until 12 weeks into pregnancy.180 The British National Formulary recommends that women taking anti-epileptic drugs wishing to become pregnant should be referred to an appropriate specialist to discuss the risk of teratogenecity.181 The size of the effect for a given dose of folic acid was recently quantified and modelling has suggested that a reduced risk is associated with higher doses (i.e. 5 milligrams instead of 0.4 milligrams), The practical implication of an increased dose of folic acid has yet to be investigated.182,183

RECOMMENDATION

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. [A]

3.12. Susceptibility to rubella

Rubella infection during pregnancy is associated with a significant teratogenic risk to the fetus, resulting in multiple congenital abnormalities.184 [Evidence level 2b] The introduction of the rubella vaccine has resulted in a decrease of rubella infections and infants with congenital rubella syndrome. The reported proportion of infertile women who were rubella susceptible ranged from 2% to 12%.185–188 [Evidence level 3] The rubella vaccine is a live attenuated virus; thus, when vaccination is given conception should be deferred for one month.

RECOMMENDATION

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. [D]

3.13. Cervical cancer screening

The reported proportion of infertile women with abnormal cervical smears ranges from 5% to 13%.186,188 [Evidence level 3] As part of the national screening programme, women between the age of 20 years and 64 years are offered cervical screening every three years or five years. Around 60% of health authorities invite women every three years and 15% have a mixed policy, inviting women every three to five years, depending upon their age.189 Abnormal cervical cytology that is overlooked may lead to increased delay in fertility treatment186 because treatment of cervical intraepithelial neoplasia is more complicated during pregnancy.

RECOMMENDATION

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. [GPP]

3.14. Defining infertility

The United Nations defines reproductive health as ‘a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity in all matters relating to the reproductive system and to its functions and processes’.190 [Evidence level 4] Infertility should, therefore, be considered to be a disease process worthy of investigation and treatment.

Infertility has been defined as failure to conceive after frequent unprotected sexual intercourse for one or two years.1,3,191–213 Diagnosis of infertility based on a failure to conceive within one year can exaggerate the risk of infertility, since about 50% of women who do not conceive in the first year are likely to do so in the second year.118,119

The prevalence of infertility in European countries is around 14%, affecting one in seven couples.1,3,193,196,197,201–205,208,210,212,214,215 Data from historical populations estimate the average prevalence of infertility to be 5.5%, 9.4% and 19.7%, respectively, at ages 25–29 years, 30–34 years and 35–39 years.216

The first consultation should include an assessment of the perceived fertility problem. For many couples, information about normal patterns of conception will provide reassurance that they are likely to have a good chance of conception. However, there should also be a specific enquiry about the medical, surgical, sexual, contraceptive and pregnancy history and a general physical examination to detect abnormalities, including measurement of height and weight to calculate BMI to identify couples who are likely to experience delays in conception.217 Couples should be offered information about lifestyle such as smoking, alcohol intake, occupational factors and diet which may impact on their fertility.

RECOMMENDATIONS

Infertility should be defined as failure to conceive after regular unprotected sexual intercourse for 2 years in the absence of known reproductive pathology. [D]

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 HIV should be referred to centres that have appropriate expertise and facilities to provide safe risk-reduction investigation and treatment. [GPP]

Copyright © 2004, National Collaborating Centre for Women’s and Children’s Health.

Apart from any fair dealing for the purposes of research or private study, criticism or review, as permitted under the Copyright, Designs and Patents Act, 1988, no part of this publication may be reproduced, stored or transmitted in any form or by any means, without the prior written permission of the publisher or, in the case of reprographic reproduction, in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK. Enquiries concerning reproduction outside the terms stated here should be sent to the publisher at the UK address printed on this page.

The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore for general use.

Cover of Fertility
Fertility: Assessment and Treatment for People with Fertility Problems.
NICE Clinical Guidelines, No. 11.
National Collaborating Centre for Women's and Children's Health (UK).
London (UK): RCOG Press; 2004 Feb.

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