Chapter 87: Gynaecology

Reproductive Physiology

Themenstrual cycle is under the control of circulating hormones produced within the hypothalamic–pituitary–ovarian axis and works as part of a negative feedback pathway (Figure S87.1). Gonadotropin-releasing hormone is produced by the hypothalamus and, in turn, stimulates the anterior pituitary to produce and secrete follicle-stimulating hormone (FSH) and luteinising hormone (LH). FSH and LH act on the ovary (mainly granulosa and theca cells, respectively), controlling folliculogenesis (oocyte development) and ovulation. The ovary is responsible for the production of the hormones oestrogen, progesterone and androgen. These hormones have an effect on a number of structures within the body, principally the endometrium, which prepares itself to receive a fertilised oocyte (embryo) during the course of the menstrual cycle. In the first half (proliferative or follicular phase) of the cycle, following menstruation, the endometrium starts to proliferate in response to oestrogen produced by the growing ovarian follicle(s). The endometrium becomes thick and spongy during this phase of the cycle and is associated with considerable angiogenesis.

Ovulation occurs midcycle following an FSH and LH surge, i.e. 14 days prior to the onset of the next menstrual cycle, which is equivalent to day 14 of a 28-day cycle (day 1 is defined as the first day of menstruation). After ovulation the remnant follicle is transformed into a corpus luteum, which is responsible for the immediate production of progesterone.

Figure S87.1

Endocrine cycle. E2, oestrogen; FSH, follicle-stimulating hormone; LH, luteinising hormone; P, progesterone.

During the second half (secretory or luteal phase) of the cycle, the endometrium thickens further under the influence of progesterone in preparation to receive the embryo.

Fertilisation takes place within the ampullary region of the fallopian tube, usually within 24 hours after ovulation. The fertilised oocyte (zygote) is then transported along the fallopian tube into the uterine cavity through movement of cilia and tubal musculature, implanting into the endometrium approximately 5–6 days after ovulation. Through the secretion of human chorionic gonadotropin (HCG) from the syncytiotrophoblasts, the corpus luteum is signalled to maintain progesterone production. If fertilisation does not occur, or if the fertilised oocyte fails to implant, the endometrium is shed as the HCG signal is missing or lost, leading to a fall in progesterone (and oestrogen) levels. Menstruation, (a ‘period’) lasts on average 4 days but can range between 2 and 7 days. Typically, 40 mL of blood is lost during each period; heavy menstruation is described when more than 80 mL of blood loss occurs, which is difficult to objectively assess and relies upon a careful history including the number of pads used, passage of clots and history of flooding whereby, there is an overflow of blood through the clothes. The whole process then starts again in the next menstrual cycle.

If fertilisation does occur, the duration of the pregnancy (gestational age) is traditionally calculated from the first day of the last menstrual period (LMP); however, ovulation may occur earlier or considerably later than day 14 and is dependent on the woman’s cycle length. Calculation of the gestational age on the basis of the LMP alone may thus be inaccurate, and explains the alternative practice of calculating gestational age using ultrasound measurements of fetal size, ideally during the first trimester.

Early Pregnancy Complications

Miscarriage

A miscarriage is defined as the loss of an intrauterine pregnancy at less than 22 weeks’ gestation. An early miscarriage refers to a pregnancy loss before 12 weeks’ gestation (‘first trimester’).

A late miscarriage refers to a pregnancy loss between 12 and under 22 weeks’ gestation (‘second trimester’). Approximately 20% of pregnancies will miscarry. This number, however, is highly influenced by maternal age and can reach approximately 50% in a 45-year-old woman.

A miscarriage can be diagnosed on transvaginal ultrasound scan in the absence of a visible fetal heartbeat with a crown-rump length (CRL) of 7.0 mm or more, or, in the absence of a fetal pole, in the presence of a mean sac diameter (MSD) of 25.0 mm or more. In the absence of this criterion, or when the dates of the LMP are uncertain, a repeat ultrasound scan should be offered a minimum of 7 days later before making a diagnosis. The gestational age from the LMP alone should not be used to determine whether fetal cardiac activity should be visible.

A miscarriage often begins with painless vaginal bleeding, at which point it is defined as a threatened miscarriage. The bleeding may then become heavier with associated uterine cramps and opening of the cervical os, at which point it is defined as an inevitable miscarriage. Blood clots and the products of conception (i.e. fetal and placental tissue) are passed through the cervical os until the uterus is emptied (defined as a complete miscarriage). If some of the products of conception are retained within the uterus, this is referred to as an incomplete miscarriage. A missed miscarriage occurs when no fetal cardiac activity can be detected on ultrasound scan and no clinical signs of a miscarriage, as described above, are present. Management of a miscarriage ranges from expectant management to medical or surgical intervention. In the UK, the National Institute for Health and Care Excellence (NICE) recommends expectant management for 7–14 days as first-line treatment in those without contraindications, such as heavy bleeding or signs of sepsis, as long as it is acceptable to the woman. For medical management, medications such as prostaglandins can be given that promote uterine contractions and cervical softening. Surgical management of a miscarriage (SMM) can be conducted using manual vacuum aspiration under local anaesthesia, or surgically under general anesthesiasia. The operation involves passing a plastic suction curette through the cervical opening and into the uterine cavity. SMM should be considered in the presence of persistent excessive bleeding, haemodynamic instability, evidence of infected retained products of conception or suspected gestational trophoblastic disease. Bleeding following a miscarriage can last for approximately 2 weeks. Persistent or excessive bleeding should be investigated for a possible incomplete procedure or retained products of conception. Serious operative complications include uterine perforation (1–15 in 1000 women) with the possibility of intra-abdominal trauma (e.g. bowel damage), cervical tears (<1 in 1000 women), haemorrhage (risk of needing a blood transfusion 0–3 in 1000 women) and infection (40 in 1000 women). Approximately 3–18 in 1000 women may require a repeat surgical evacuation with 40 in 1000 women having evidence of retained products of conception. The incidence of intrauterine adhesion formation is quoted at 16.3–18.5% following SMM (with a pooled incidence of 19% following an early spontaneous pregnancy loss or expectant, medical or surgical intervention for an early miscarriage). Furthermore, no significant differences have been recorded on long-term fertility outcomes following expectant, medical or surgical management but the data are limited by the paucity of available evidence. The frequency and severity of intrauterine adhesion formation is, however, considered to be proportional to the number of uterine surgical procedures performed.

In view of the potential risk of organ damage, women should concomitantly be consented for a laparoscopy and laparotomy.

Cervical priming should be considered in nulliparous women. The aim of cervical priming prior to SMM is to reduce the force and need for mechanical dilatation of the cervix and, thus, improve the surgical ease of the procedure. This, however, has not been adequately reported upon in studies.

A causal association has also been identified between repeated SMM and the subsequent risk of preterm birth (odds ratio 1.29 for preterm birth at less than 37 weeks’ gestation).

Anti-D immunoglobulin should be prescribed to all non-sensitised rhesus (Rh)-negative women undergoing surgical treatment of a miscarriage, in cases involving excessive bleeding being managed conservatively or medically under 12 weeks’ gestation as well as any sensitising event over 12 weeks’ gestation.

Vaginal bleeding in early pregnancy may also result from a local cause such as a cervical lesion (which may first manifest itself as bleeding after intercourse) or, rarely, trauma.

Gestational Trophoblastic Disease

Gestational trophoblastic disease comprises a group of premalignant disorders (complete [arise as a consequence of duplication of a single sperm following fertilisation or dispermic fertilisation of an empty ovum] and partial [contain two sets of paternal and one set of maternal haploid chromosomes] molar pregnancies [also known as hydatidiform moles]) and malignant conditions (invasive mole, choriocarcinoma, placental site trophoblastic tumour and epithelioid trophoblastic tumour). Gestational trophoblastic neoplasia is diagnosed in conditions of persistently elevated HCG levels. The incidence is estimated to be 1 in 714 live births within the UK, highest in Asian populations and pregnancies at the extremes of reproductive age. Table S87.1 outlines the presenting characteristics, recommended investigations and management options.

TABLE S87.1 Presenting characteristics, recommended investigations and management options for gestational trophoblastic disease.

Presenting characteristics
Common symptoms	Rare presentations	Very rare signs
Irregular vaginal bleeding Positive pregnancy test	Hyperemesis Excessive uterine enlargement Hyperthyroidism Early-onset pre-eclampsia Abdominal distension	Haemoptysis Seizures
Investigations
Ultrasound	Polypoid mass and thickened cystic appearance of the villous tissue with no identifiable gestational sac. Partial molar pregnancies are associated with an enlarged placenta or cystic changes within the decidual reaction in association with either an empty sac or a delayed miscarriage. In addition, the transverse-to-anteroposterior dimension ratio of the gestational sac is >1:1.5
Serum βHCG levels	Significantly higher Other causes should also be considered such as malignant germ cell tumours and epithelial cancers, including bladder, breast, lung, gastric and colorectal cancers
Management
Suction curettage	Cervical priming can be undertaken if indicated and has not been linked to a higher risk of needing chemotherapy in a small case–control study The risk of gestational trophoblastic neoplasia is estimated to be 16-fold higher for medical management than surgical treatment Avoidance of oxytocic agents is recommended secondary to the risk of embolisation and dissemination of trophoblastic tissue leading to respiratory distress syndrome
Postoperative care
Anti-D prophylaxis	Recommended in Rh-negative women
Urinary pregnancy test	A repeat should be performed 3 weeks after the procedure
Referral to a gestational trophoblastic disease centre	Considered in cases of persistently elevated serum βHCG levels

Termination of Pregnancy

The Abortion Act 1967 decriminalised terminations of pregnancy undertaken on certain grounds by registered practitioners within the UK. This helped to give women a choice of whether to continue with a pregnancy or to end it. Currently, an abortion can be performed up to the 24th week of pregnancy under this Act. Restrictions, however, have been removed for late abortions in cases of risk to the woman’s life, fetal abnormality or grave physical and mental injury to the woman.

In 2018, the Republic of Ireland also made abortions legal, but only up to the 10th week of pregnancy. Some countries have different policies and still consider an abortion a criminal act, except in very particular circumstances.

In the UK the HSA1 form must be completed prior to undertaking an abortion by two registered medical practitioners under Section 1 of the Abortion Act 1967 and must be kept with the patient’s records for 3 years from the date of termination. The form outlines the grounds under which the termination was taken (A, B, C, D or E):

1. The continuance of the pregnancy would involve risk to the life of the pregnant woman greater than if the pregnancy were terminated;
2. The termination is necessary to prevent grave permanent injury to the physical or mental health of the pregnant woman;
3. The pregnancy has NOT exceeded its 24th week and the continuance of the pregnancy would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the pregnant woman;
4. The pregnancy has NOT exceeded its 24th week and the continuance of the pregnancy would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of any existing child(ren) of the family of the pregnant woman;
5. There is a substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously handicapped.

The commonest cited indication for an abortion carried out secondary to social reasons is clause C: continuation of the pregnancy would cause physical or mental harm to the mother. A termination of pregnancy can be managed similarly to management of a miscarriage: medically or surgically (manual vacuum aspiration or surgical evacuation). The risks associated with surgical treatment increase with increased gestational age. Anti-D is recommended in Rh-negative women undergoing a surgical termination but not in women ≤10 weeks’ gestation undergoing medical management. A pregnancy test is recommended 3 weeks following treatment to confirm resolution.

Contraception

Contraceptive methods protect against pregnancy. There are many different methods available (Table S87.2) but most methods of contraception will not protect against a sexually transmitted infection (STI). Condoms (external condoms in a male partner or internal condoms in a female partner) are the only method that is able to protect against both a pregnancy and STI. Effective contraception is recommended for at least 2 years after the last period if aged under 50 years and for 1 year after the last period if aged over 50 years, for those wishing to avoid a pregnancy.

TABLE S87.2 Contraceptive methods.

Contraceptive method	Efficacy	Mechanism of action	Advantages	Disadvantages
Daily preparations (tablets)/patches/vaginal rings
Natural family planning/ withdrawal technique	76–99%	Avoidance of the fertile window (4 days prior to ovulation to 2 days afterwards)	No associated adverse effects	Not effective with irregular menstrual cycles
Combined contraceptive pill (contains both oestrogen and progestogen)	91–99%	Inhibition of ovulation, prevention of sperm transport through the cervix, inhibition of implantation	Role in the management of painful, heavy or irregular menstruation Reduction in the risk of ovarian, endometrial and colon cancer Resumption of fertility upon cessation	Not recommended in overweight women and smokers Associated with a risk of VTE, breast cancer and cervical cancer dependent on the oestrogen dose, mode of administration and progestogen component Common complaints can include headaches, nausea, mood changes, breast tenderness and irregular bleeding in the first few months Efficacy is diminished with missed pills, vomiting and diarrhoea and enzyme inducers
Progestogen-only pill	91–99%	Inhibition of ovulation in some cycles and prevention of sperm transport through the cervix	Suitable in women >35 years of age, smokers and those in whom oestrogen use is contraindicated May simultaneously manage premenstrual symptoms and dysmenorrhoea	Common symptoms include irregular menstruation, acne, breast tenderness, weight change and headaches Ovarian cysts have been identified following use Ineffective if taken >3 hours late or following vomiting or diarrhoea and enzyme inducers
Contraceptive patch (contains oestrogen and progestogen)	91–99%	Inhibition of ovulation, prevention of sperm transport through the cervix, inhibition of implantation	Efficacy is unaffected by vomiting and diarrhoea May simultaneously manage heavy menstrual bleeding, dysmenorrhoea and lead to improvement in symptoms of acne	Not recommended in overweight women and smokers >35 years of age Associated with a low risk of VTE, breast cancer and cervical cancer dependent on the oestrogen dose, mode of administration and progestogen component Common complaints can include headaches, nausea, mood changes, breast tenderness, local skin irritation and irregular bleeding in the first few months Efficacy is diminished with enzyme inducers
Contraceptive vaginal ring (contains oestrogen and progestogen)	91–99%	Inhibition of ovulation, prevention of sperm transport through the cervix, inhibition of implantation	Efficacy is unaffected by vomiting and diarrhoea May simultaneously manage heavy menstrual bleeding, dysmenorrhoea and lead to improvement in symptoms of acne	Not recommended in overweight women and smokers >35 years of age Associated with a low risk of VTE, breast cancer and cervical cancer dependent on the oestrogen dose, mode of administration and progestogen component Common complaints can include headaches, nausea, mood changes, breast tenderness, vaginal discharge and irregular bleeding in the first few months Efficacy is diminished with enzyme inducers
Barrier contraceptives
Male condom	82–98%	Prevention of sperm transport	Effective in the prevention of STI	Efficacy is user dependent (at risk of slipping off or splitting if not applied correctly or the wrong size is used) Avoidance of spermicidal lubricated condoms is recommended as the spermicide commonly contains a chemical called nonoxinol 9, which may increase the risk of HIV infection
Female condom	79–95%	Prevention of sperm transport	Effective in the prevention of STI Additional spermicide is not needed or recommended	Efficacy is user dependent (the penis is at risk of entering the area between the vaginal wall and condom)
Diaphragm/cap with spermicide	71–96%	Prevention of sperm transport		Extra spermicide is recommended every time the user has sex and if placed more than 3 hours prior to sex Needs to be left in place for 6 hours after sex
Long-acting reversible contraceptives
Contraceptive injection (contains progestogen), e.g. Noristerat, Depo- Provera, Sayana Press	94–99%	Inhibition of ovulation, prevention of sperm transport through the cervix, inhibition of implantation	Lasts for 8–13 weeks dependent on the preparation May also reduce heavy, painful periods Not affected by other medicines, diarrhoea or vomiting	Periods may cease, become irregular or last longer Periods and fertility can take time to resume upon cessation Some women complain of weight gain
Contraception implant (contains progestogen), e.g. Implanon	99%	Inhibition of ovulation, prevention of sperm transport through the cervix, inhibition of implantation	Lasts for 3 years but can be taken out sooner Periods and fertility will return upon removal of the implant	Periods may cease, become irregular or last longer Requires a small procedure to fit and remove Efficacy is diminished with enzyme inducers
Intrauterine device, e.g. copper coil	>99%	Prevention of sperm transport through the uterus and inhibition of implantation	Duration of use is dependent on the type (5–10 years) If inserted after the age of 40 years, it can remain in situ until the menopause Unaffected by other medication	Unsuitable for use in those at risk of a pelvic infection, greatest within the first 20 days after insertion Periods may be become heavier, more prolonged and painful
Intrauterine system (releases progestogen), e.g. Mirena coil	>99%	Prevention of sperm transport through the cervix and inhibition of implantation	Duration of use is dependent on the type (3–5 years). If inserted after the age of 45 years, it can remain in situ until the menopause Unaffected by other medication May simultaneously manage heavy menstrual bleeding and dysmenorrhoea	Common complaints include irregular menstruation and spotting in the first 6 months Unsuitable for use in those at risk of a pelvic infection, greatest within the first 20 days after insertion Increased report of ovarian cyst formation
Permanent methods
Tubal occlusion performed either hysteroscopically or laparoscopically	Failure rate: Overall: 1:200 Hysteroscopically: 1:500 over 5 years	The fallopian tubes are cut (ligated), sealed or blocked either laparoscopically with the use of, for example, Filshie clips or hysteroscopically using microinserts. This prevents fertilisation	Periods are unaffected Unaffected by other medication	Risks include those associated with the surgical procedure and of an ectopic pregnancy if tubal occlusion is incomplete Additional contraception is required until the next menstrual cycle Permanent and irreversible on the NHS
Vasectomy	Failure rate: approx. 1:2000	The vas deferens are cut, sealed or tied	Can be performed under local anaesthesia	Additional contraception is required until a semen analysis demonstrates azoospermia
Emergency contraception
Intrauterine device, e.g. copper coil	<1% will conceive if used as an emergency contraceptive method	Prevention of sperm transport through the uterus and inhibition of implantation	Can be inserted up to 5 days after unprotected intercourse or up to 5 days after ovulation
Morning after pill, e.g. Levonelle or ellaOne		Levonelle delays or inhibits ovulation ellaOne prevents progesterone from working normally and can also delay or inhibit ovulation	Levonelle can be taken up to 3 days after unprotected intercourse ellaOne can be taken up to 5 days after unprotected intercourse	Common complaints include a headache or gastrointestinal symptoms An additional method of contraception is recommended if vomiting occurs within 2–3 hours after taking the tablets

Pelvic Inflammatory Disease

The overwhelming majority of cases of PID are caused by ascending infection, most commonly sexually transmitted, leading to endometritis, salpingitis, tubo-ovarian abscess formation and/or pelvic peritonitis. Rarer causes include spread from other pelvic organs, e.g. the appendix. Chlamydia trachomatis is the most common organism responsible for PID, accounting for 14–35% of cases; the prevalence of Neisseria gonorrhoeae varies depending upon the locality. Other organisms commonly found in the vagina may also be implicated: Gardnerella vaginalis, anaerobes (including Prevotella, Atopobium and Leptotrichia) and Mycoplasma genitalium. Risk factors include young age at first sexual activity, a high number of sexual partners and current use of an intrauterine device (IUD) (typically within the first 4–6 weeks after insertion); infection may also follow a surgical procedure such as termination of pregnancy.

There are no definitive criteria for making a diagnosis of PID. Most clinicians rely instead upon the presence of one or more of the following features, which are suggestive of the diagnosis:

• lower abdominal pain and tenderness, more commonly bilateral;
• deep dyspareunia (pain on intercourse);
• abnormal vaginal bleeding, including postcoital bleeding, intermenstrual bleeding and menorrhagia;
• dysmenorrhoea;
• abnormal cervical discharge, commonly purulent;
• cervical excitation and adnexal tenderness;
• fever >38°C;
• elevated white blood cells (neutrophils) and platelets.

It should be noted that some patients are asymptomatic or may present with non-specific symptoms, and a high degree of clinical suspicion is needed to avoid a delay in making the diagnosis.

The differential diagnoses include:

• endometriosis;
• urinary tract infection;
• appendicitis;
• gastrointestinal dysfunction;
• ectopic pregnancy;
• adnexal torsion/ovarian cyst accident;
• diverticulitis.

Raised inflammatory markers (white cell count, neutrophil count and C-reactive protein) support the diagnosis. Ultrasound scan assessment of the pelvis can detect the presence of hydrosalpinges and/or a tubo-ovarian abscess. Doppler ultrasound can detect increased blood flow associated with infection and may be useful, but it cannot differentiate between PID and other causes of increased vascularity such as endometriosis. Magnetic resonance imaging (MRI) or computed tomography (CT) scanning of the pelvis may be helpful in differentiating PID from alternative diagnoses but are not indicated routinely. MRI, when available, is preferable since it provides high-resolution images and avoids ionising radiation in women of reproductive age. All women with suspected PID should be screened for N. gonorrhoeae and C. trachomatis; however, an absence of infection does not exclude a diagnosis of PID. C. trachomatis is an intracellular organism; therefore, samples obtained for diagnostic purposes should contain cellular material. If an endocervical swab is to be used to obtain a specimen, it is important to clean the cervix of excessive discharge before inserting the swab inside the cervical os (Summary box S87.2).

Current guidelines recommend a low threshold for empirical treatment (Summary box S87.3) because the consequences of failing to treat acute PID effectively are extremely significant: chronic pelvic pain; infertility; increased risk of an ectopic pregnancy (6%; approximately 10 times higher than the background population); and Fitz-Hugh–Curtis syndrome (an extrapelvic manifestation of PID associated with right upper quadrant pain, most probably resulting from the inflammation of the liver capsule and diaphragm). Approximately 20% of women treated for PID will become infertile, secondary to tubal damage; >50% of tubal factor infertility cases arise from infection secondary to Chlamydia; however, interestingly, many of these women do not report a history of PID.

Treatment should be commenced as soon as samples have been obtained for culture, without the need to wait for the results, but changing the antibiotics once the sensitivities become available; it should include a broad-spectrum antibiotic against coliforms and anaerobic species which are responsible for secondary infection. Contact tracing (a minimum of 6 months within the onset of symptoms) and treatment are essential.

The majority of suspected cases are treated within the community, with a review advised after 72 hours. Hospital admission is advisable if there is doubt about the diagnosis or if the symptoms/signs are severe. If an IUD is in situ, current guidance suggests that it can be left in place in the context of mild to moderate disease with a review after 48–72 hours. If the patient remains clinically unwell, it should be removed. Emergency hormonal contraception following removal of an IUD may be appropriate for some women who have had otherwise unprotected intercourse in the preceding 7 days. Coun- selling should also cover future contraception.

A tubo-ovarian abscess can develop in severe cases of PID; this is where the fallopian tube and ovary become blended into a single, pus-filled, inflammatory mass, which is usually adherent to the uterus and surrounding bowel. The infection may have progressed from a milder form of PID or, increasingly, it may result from the introduction of infection or bowel damage at transvaginal oocyte aspiration in a patient undergoing in vitro fertilisation. Modern medical practice is to manage tubo-ovarian abscesses (Figure S87.2) conservatively unless the patient fails to respond to intravenous antibiotics and systemic support. The response is judged to be inadequate if the woman remains systemically unwell, her symptoms do not improve, fever is not reduced, the white blood cell count does not fall and there is no radiological evidence of the abscess becoming smaller. In such circumstances, surgical treatment is necessary, i.e. adhesiolysis and drainage of the abscess at laparotomy or laparoscopy. As most women with a tubo- ovarian abscess are in the reproductive years, the intention is always to be as conservative as possible at surgery. Rarely, however, if the abscess has ruptured (Figure S87.3) and the patient is extremely ill, then a hysterectomy and bilateral salpingo-oophorectomy may become necessary.

Abscess drainage under radiological guidance, e.g. a transgluteal approach via the greater sciatic foramen under CT, is sometimes performed. Transvaginal ultrasound-guided aspiration has also been advocated. It is clearly less invasive and there are claims that the method is as effective as surgery; however, it carries additional risks such as bowel damage and tracking of the infection along the root of entry of the needle.