Sex, Infertility and Contraception

1. Introduction
2. Sexual Response and Its Physiology
   • The Sexual Response Cycle
   • Erection, Emission and Ejaculation
   • Sexual Dysfunction
3. Infertility
   • Definitions and Epidemiology
   • Causes of Female Infertility
   • Causes of Male Infertility
   • Investigation
   • Principles of Treatment
4. Contraception
   • Effectiveness and Choice
   • Combined Hormonal Contraception
   • Progestogen-Only Pill
   • Long-Acting Reversible Contraception
   • Barrier Methods
   • Sterilisation
   • Emergency Contraception
   • Fertility Awareness
5. Summary
6. Quiz

• The sexual response cycle (excitement, plateau, orgasm, resolution) depends on parasympathetic nerves, which widen blood vessels so that the genitals fill with blood (engorgement). Sympathetic nerves drive emission (the movement of semen into the urethra). Erection depends on nitric oxide raising cyclic GMP (cGMP, a messenger that relaxes smooth muscle) in penile smooth muscle. PDE5 inhibitors (phosphodiesterase type 5 inhibitors, such as sildenafil) treat erectile dysfunction by blocking the enzyme that breaks cGMP down.
• Infertility is conventionally diagnosed after 12 months of regular unprotected intercourse without conception. Not everyone waits a year. Offer referral at presentation if the person trying to become pregnant is aged 36 or over, or if either partner has a suspected or known cause or a history of risk factors for infertility. About 1 in 7 UK couples is affected. In about 1 in 4 couples, no cause is found.
• Investigation runs in parallel for both partners. In the woman it centres on a day-21 progesterone test, pelvic ultrasound and a test of tubal patency (whether the fallopian tubes are open). Other hormone tests are used only when indicated: gonadotrophins (the pituitary hormones follicle-stimulating hormone, FSH, and luteinising hormone, LH) if cycles are irregular, and prolactin (a pituitary hormone that suppresses ovulation when raised) or thyroid tests in selected cases. In the man it centres on semen analysis.
• Modern contraception is best understood by mechanism (combined oestrogen and progestogen, where a progestogen is a progesterone-like hormone; progestogen-only; intrauterine; barrier; sterilisation; fertility awareness) and effectiveness (long-acting reversible methods are markedly more effective with typical use than user-dependent methods). Three options are licensed for emergency contraception. Levonorgestrel works up to 72 hours after sex. Ulipristal acetate works up to 120 hours after sex. The copper intrauterine device is the most effective. It can be fitted within 5 days (120 hours) of unprotected sex, or within 5 days of the earliest expected ovulation, whichever is later.

Introduction

Sex, infertility and contraception sit together in the curriculum because they follow one chain of events. The physiology of intercourse and conception explains how couples become pregnant. Understanding why some couples do not conceive leads into infertility medicine. Contraception is the deliberate interruption of that same chain (most methods are reversible, but sterilisation is permanent). This article addresses each topic at the level expected of a UK pre-clinical student. The underlying anatomy and the menstrual cycle are covered in three lessons: ‘Anatomy of the Man’, ‘Anatomy of the Woman’ and ‘The Menstrual Cycle and Menstrual Abnormalities’.

Sexual Response and Its Physiology

The Sexual Response Cycle

The classical Masters and Johnson model divides the human sexual response into four phases:

1. Excitement: central arousal (in the brain), with peripheral effects driven by parasympathetic outflow. These are penile and clitoral engorgement (filling with blood), vaginal lubrication and labial swelling.
2. Plateau: sustained vasocongestion (the blood vessels of the genitals stay filled with blood). In the male, the testes are drawn upwards and the bulbourethral glands (small glands beside the urethra) secrete pre-ejaculate. In the female, the outer third of the vagina narrows (the "orgasmic platform").
3. Orgasm: rhythmic contractions of the pelvic floor muscles and genital smooth muscle. In the male this is coordinated with emission (sympathetic) and ejaculation (somatic, via the pudendal nerve, which supplies the pelvic floor and genitals). In the female, orgasm needs no accompanying secretion.
4. Resolution: vasocongestion subsides over minutes. The male enters a refractory period (a time when further orgasm is not possible). Women do not have a fixed refractory phase.

A useful memory aid is that parasympathetic outflow drives erection and sympathetic outflow drives emission. Ejaculation itself is a somatic reflex. These steps are coordinated by spinal centres in the lower spinal cord (the lumbar and sacral segments) with input from higher centres. The principles of autonomic control are set out in Autonomic Nervous System Introduction.

Erection, Emission and Ejaculation

An erection is a vascular event. Sexual stimulation triggers parasympathetic outflow from the second to fourth sacral spinal segments (S2-S4) via the cavernous nerves (the small nerves that supply the erectile tissue of the penis). These nerves release nitric oxide (NO) in the penile vascular smooth muscle. NO activates guanylate cyclase (the enzyme that makes cGMP) and raises intracellular cyclic GMP (cGMP). cGMP relaxes the smooth muscle of the helicine arteries (small coiled arteries) supplying the corpora cavernosa (the two columns of erectile tissue). The corpora fill and compress the venous outflow against the rigid tunica albuginea (the tough fibrous sheath around the erectile tissue), and the penis becomes erect.

cGMP is broken down by phosphodiesterase type 5 (PDE5), so PDE5 controls how long the relaxation lasts. PDE5 inhibitors (sildenafil, tadalafil, vardenafil) boost the same NO/cGMP pathway and are the first-line drug treatment for erectile dysfunction. They are contraindicated with nitrates (angina drugs such as glyceryl trinitrate, GTN), and with nicorandil (an angina drug with a nitrate-like action) and amyl nitrate (‘poppers’). The combined build-up of cGMP can cause profound hypotension (a very low blood pressure).

Once the male is sufficiently aroused, emission and then ejaculation follow:

• Emission (sympathetic outflow from the lower thoracic and upper lumbar spinal segments, T11-L2): smooth-muscle contraction of the vas deferens (the tube carrying sperm from the testis), the seminal vesicles (glands that add fluid to semen) and the prostate. This deposits semen into the prostatic urethra. The internal urethral sphincter contracts to prevent retrograde ejaculation into the bladder.
• Ejaculation (somatic, via the pudendal nerve, S2-S4, which supplies the pelvic floor and genitals): rhythmic contractions of the bulbospongiosus (the muscles at the base of the penis) and the ischiocavernosus muscles (which cover the roots of the penis) propel semen out of the urethra.

Failure of the internal urethral sphincter to close produces retrograde ejaculation. Sperm passes back into the bladder. The post-coital urine looks cloudy, and the man appears infertile despite preserved orgasm. Causes include prostatectomy (removal of the prostate) and α-blockers (drugs that relax smooth muscle), such as tamsulosin, used for benign prostatic enlargement.

Sexual Dysfunction

Sexual dysfunction is common and frequently has both physical and psychological components.

In men, the principal categories are:

• Erectile dysfunction: inability to achieve or maintain an erection. Causes include:
  • vascular disease (the most common cause in older men; erectile dysfunction shares its risk factors with artery disease);
  • neurological disease (e.g. autonomic neuropathy, damage to the nerves that control automatic body functions, in diabetes; spinal cord injury);
  • endocrine causes (hypogonadism, meaning low sex hormone production; hyperprolactinaemia, meaning raised prolactin; thyroid disease);
  • drugs (antihypertensives, particularly thiazides, a type of diuretic, and β-blockers, which slow the heart and lower blood pressure; antidepressants, particularly selective serotonin reuptake inhibitors, SSRIs; alcohol);
  • psychogenic causes (situational, performance-related).
  Loss of nocturnal or morning erections is a clue to a physical (organic) rather than a psychological cause.
• Premature ejaculation: ejaculation occurring with minimal stimulation; treated with behavioural techniques and/or short-acting SSRIs (dapoxetine).
• Low libido (hypoactive sexual desire, meaning persistently low interest in sex): consider depression, drug effect and hypogonadism.

In women, the principal categories are disorders of desire, arousal, orgasm, and sexual pain (dyspareunia, meaning painful intercourse, and vaginismus, meaning involuntary tightening of the vaginal muscles). Pelvic problems should be considered alongside hormonal and psychological factors. These include endometriosis (womb-lining-like tissue growing outside the uterus), vulvodynia (chronic vulval pain), adhesions (bands of scar tissue) and postpartum changes (changes after childbirth). Postmenopausal women may have vaginal atrophy (thinning and drying of the vaginal lining), which produces dyspareunia. Vaginal atrophy is treated effectively with topical oestrogens.

Infertility

Definitions and Epidemiology

Infertility is the failure of a couple to conceive after 12 months of regular unprotected intercourse. Offer initial assessment whenever people are concerned about delayed conception. Without a suspected or known cause, offer both partners further assessment and investigation after one year of unprotected vaginal intercourse. Offer specialist referral at presentation if the person trying to become pregnant is aged 36 or over, or either partner has a suspected or known cause or predisposing factors. A miscarriage or ectopic pregnancy (a pregnancy that implants outside the uterus) during the one-year investigation timeframe does not restart the one-year clock. See NICE NG257 recommendations 1.16.1, 1.16.5, 1.16.7 and 1.16.8.

Infertility affects about 1 in 7 couples in the UK. NICE CKS (Clinical Knowledge Summaries, NICE's summaries for primary care) gives the main causes as follows. The figures overlap, because some couples have more than one cause:

• Male factor: 30% of couples.
• Ovulatory disorders (the woman does not release an egg regularly): 25% of couples.
• Tubal damage: 20% of couples.
• Uterine or peritoneal disorders (problems in the womb or the lining of the pelvis): 10% of couples.
• Unexplained: about 25% of couples have no identifiable cause.

The strongest single factor in fertility is female age. The chance of conceiving falls steeply from the late 30s and very steeply after 40. This reflects both a falling number of eggs (ovarian reserve) and falling egg quality (a rising rate of aneuploidy, meaning an abnormal number of chromosomes).

Causes of Female Infertility

Female causes are conventionally split by anatomical site:

• Ovulatory disorders (about 25% of couples with infertility):
  • Polycystic ovary syndrome (PCOS): the commonest cause of anovulatory infertility in the UK; characterised by oligo- or anovulation, clinical or biochemical hyperandrogenism (signs or blood tests showing excess androgens, the male-type hormones), and polycystic ovarian morphology on ultrasound (Rotterdam criteria, two of three).
  • Hypothalamic amenorrhoea (absent periods because the hypothalamus reduces its signals to the pituitary): from low body weight, intense exercise or severe stress. It is reversed by restoring energy balance.
  • Hyperprolactinaemia (raised prolactin): from prolactinoma (a prolactin-secreting pituitary tumour), drugs (antipsychotics, metoclopramide) or primary hypothyroidism. It suppresses gonadotrophin-releasing hormone (GnRH) and so suppresses ovulation. See Pituitary Disorders.
  • Premature ovarian insufficiency (POI): menopause before age 40, with raised follicle-stimulating hormone (FSH), low oestradiol (the main oestrogen) and low anti-Müllerian hormone (AMH, a hormone made by the ovarian follicles that reflects the egg supply).
  • Thyroid disease: both hyper- and hypothyroidism affect ovulation.
• Tubal disease (about 20% of couples with infertility):
  • Previous pelvic inflammatory disease (infection of the upper female genital tract), particularly chlamydia.
  • Previous ectopic pregnancy or pelvic surgery.
  • Endometriosis with adhesion formation.
• Uterine and cervical factors:
  • Submucosal fibroids (benign muscle growths under the uterine lining) distorting the cavity.
  • Endometrial polyps (small growths on the lining of the uterus).
  • Intrauterine adhesions (Asherman's syndrome, scarring inside the uterine cavity).
  • Congenital uterine anomalies (e.g. septate uterus, where a wall of tissue divides the uterus).
  • Cervical stenosis (narrowing of the cervical canal) after surgery (e.g. large loop excision of the transformation zone, LLETZ).
• Endometriosis: can cause infertility through tubal adhesion, distorted pelvic anatomy and unclear effects on egg quality and implantation.

Causes of Male Infertility

Male infertility is investigated through semen analysis. The principal mechanistic groups are:

• Pre-testicular (hormonal): hypogonadotrophic hypogonadism (low sex hormones caused by low pituitary hormones) from pituitary disease, Kallmann syndrome (a genetic cause of absent puberty and absent sense of smell), hyperprolactinaemia or anabolic steroid use (which suppresses the hormone signals running from the brain to the testes, the hypothalamic-pituitary-gonadal axis).
• Testicular (primary gonadal failure): cryptorchidism (undescended testis), Klinefelter syndrome (47,XXY, males with an extra X chromosome), Y-chromosome microdeletions (small missing pieces of the Y chromosome), mumps orchitis (inflammation of the testis), chemotherapy or radiotherapy, and varicocele (enlarged veins in the scrotum; the raised scrotal temperature impairs spermatogenesis, which is sperm production).
• Post-testicular (obstructive): congenital bilateral absence of the vasa deferentia (CBAVD), which occurs in cystic fibrosis, previous infection (epididymitis, which is inflammation of the epididymis where sperm are stored; gonorrhoea), previous vasectomy, ejaculatory duct obstruction, retrograde ejaculation.
• Lifestyle and environmental: smoking, alcohol, obesity, anabolic steroids, tight underwear and sauna use (a raised scrotal temperature is linked to poorer semen quality, but it is uncertain whether changing underwear improves fertility).

Investigation

Investigation runs in parallel for both partners.

Female partner:

• Ovulation: day-21 progesterone, taken in the mid-luteal phase (the second half of the cycle, after ovulation): a value above 30 nmol/L confirms ovulation. If cycles are prolonged and irregular, the test is done later in the cycle (for example day 28 of a 35-day cycle) and repeated weekly until the next period starts.
• Ovarian reserve: NICE (2026) says not to use anti-Müllerian hormone (AMH) to predict the chance of conceiving naturally, and not to use follicle-stimulating hormone (FSH) to predict the outcome of assisted conception. AMH or an antral follicle count (an ultrasound count of the small follicles in the ovaries) can be used to predict the response to assisted conception such as in vitro fertilisation (IVF). AMH can be sampled at any time in the cycle.
• Endocrine causes of anovulation: test only when indicated. Measure FSH and luteinising hormone (LH), together called gonadotrophins, if cycles are irregular. Measure prolactin only if there is an ovulatory disorder, galactorrhoea (milk production not linked to pregnancy) or a pituitary tumour. Measure thyroid-stimulating hormone (TSH) only if there are symptoms of thyroid disease. Total testosterone is measured if PCOS is suspected.
• Pelvic anatomy: transvaginal ultrasound for ovarian morphology, fibroids, endometrial appearance and hydrosalpinges (fluid-filled, blocked fallopian tubes).
• Tubal patency: HSG (hysterosalpingography, an X-ray test using contrast dye) is offered to women with no known comorbidity (such as pelvic inflammatory disease, previous ectopic pregnancy or endometriosis). HyCoSy (hysterosalpingo-contrast-sonography, the same test done with ultrasound) is an effective alternative where the expertise is available. Laparoscopy (keyhole surgery) with dye is offered if a comorbidity is present, so that tubal and other pelvic problems can be assessed together.
• Infection screen: chlamydia testing before tubal investigation.

Male partner:

• Semen analysis after 2-7 days of abstinence, assessing sperm concentration, total and progressive motility, and morphology against current WHO reference values. An abnormal sample is normally repeated about 3 months later, to allow one full cycle of sperm production, before it is acted upon. The exception is azoospermia (no sperm in the semen) or severe oligozoospermia (a very low sperm count). In these cases the repeat test is brought forward.
• Hormonal profile: after 2 or more abnormal semen analyses, examine the scrotum and testes and consider measuring testosterone, FSH and LH. This looks for hormonal causes that may be treatable.
• Genetic testing is targeted. Test for Y-chromosome microdeletions if there is idiopathic azoospermia (no sperm and no known cause) or a sperm concentration under 1 million per ml. Test the CFTR gene (the cystic fibrosis gene) if obstructive azoospermia or a vasal abnormality is suspected. Test the karyotype (chromosome analysis) in idiopathic azoospermia, and consider it if the sperm concentration is persistently under 5 million per ml.
• Scrotal ultrasound if a varicocele or anatomical abnormality is suspected.

Principles of Treatment

Treatment is matched to the cause:

• Lifestyle: normalise BMI (over- or underweight), stop smoking, reduce alcohol, recommend folic acid 400 micrograms daily for the female partner, from before conception until 12 weeks of pregnancy. Women at higher risk of a pregnancy affected by a neural tube defect (such as spina bifida) are advised to take 5 mg daily instead, after speaking to a doctor.
• Anovulation:
  • Letrozole: an aromatase inhibitor (a drug that lowers oestrogen production, so FSH rises). The 2023 International PCOS Guideline recommends it as the first-line drug for ovulation induction (drug treatment to bring on ovulation), in preference to clomifene, in women with PCOS who are infertile because they do not ovulate and have no other infertility factors. This use is off-label (outside the drug licence) in many countries. NICE is developing its own PCOS guideline.
  • Clomifene citrate: a selective oestrogen receptor modulator (it blocks the brain's response to oestrogen, so FSH rises); previously the standard first-line; carries a risk of multiple pregnancy.
  • Gonadotrophin injections (injected FSH, sometimes with LH, which stimulate the ovaries directly): usually reserved for cases that fail oral therapy, or used for hypogonadotrophic hypogonadism. They need ultrasound monitoring because of the risk of multiple pregnancy and ovarian hyperstimulation (an over-response of the ovaries).
  • Metformin: can be used alone in PCOS, but women should be told that other ovulation agents are more effective. It can also be added to clomifene, which improves ovulation and pregnancy rates compared with clomifene alone.
  • Treat underlying cause: dopamine agonists for hyperprolactinaemia, levothyroxine for hypothyroidism, weight restoration in hypothalamic amenorrhoea.
• Tubal disease: tubal surgery can be considered for mild disease, in centres with the right expertise. Tubal catheterisation (passing a fine tube through the blockage) can be considered for a blockage near the uterus. Otherwise in vitro fertilisation (IVF) is the usual treatment. Hydrosalpinges are treated before IVF by laparoscopic salpingectomy (removal of the tube) or tubal occlusion (blocking the tube), which improves the chance of pregnancy. Aspiration of the fluid is an option if laparoscopic surgery is high risk.
• Endometriosis: surgical excision or ablation (destroying the tissue) plus adhesiolysis (cutting scar tissue) is offered for disease that does not involve the bowel, bladder or ureter, because it improves the chance of spontaneous pregnancy. For deep disease, the benefits and risks of laparoscopic surgery are discussed. Medical suppression (combined hormonal contraception, GnRH analogues) does not improve spontaneous pregnancy rates, so it is not offered to women trying to conceive and is reserved for symptom control.
• Male factor: treatment depends on the cause. Gonadotrophin therapy is offered for hypogonadotrophic hypogonadism. Surgical correction or surgical sperm retrieval is offered for obstructive azoospermia, and surgical sperm retrieval for non-obstructive azoospermia. Radiological or surgical treatment can be considered for a varicocele with reduced semen parameters. When other treatments are unsuitable or have failed, IVF is offered. Intracytoplasmic sperm injection (ICSI, injecting a single sperm into an egg) is considered if the semen parameters are abnormal, taking account of how severe they are. Unstimulated intrauterine insemination (IUI, placing prepared sperm in the uterus) is offered only when vaginal intercourse is not possible or donor sperm is used.
• Unexplained infertility: couples are advised to keep trying for 2 years in total before treatment. Ovarian stimulation alone is not offered. After 2 years, there are two options. One is IVF. The other, as an alternative first treatment, is up to 4 cycles of IUI with ovarian stimulation (gonadotrophins) before IVF.

NICE guidance (NG257, 2026) recommends offering an initial 3 full cycles of IVF to women under 40 who meet the eligibility criteria. If they have not conceived, up to 3 further cycles can be considered after discussion. Women aged 40 or 41 who meet the criteria and have not had IVF before are offered 1 full cycle. Provision varies between integrated care boards (the local NHS bodies that commission care).

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