Early Pregnancy

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Chapter 15 Early Pregnancy

Miscarriage 308

Threatened Miscarriage 308

Inevitable Miscarriage 308

Complete Miscarriage 308

Incomplete Miscarriage 309

Missed Miscarriage 309

Other Terms 309

Early Pregnancy Loss (≤12 Weeks’ Gestation) 310

Late Pregnancy Loss (>12 Weeks’ Gestation) 313

Recurrent Miscarriage 314

Introduction and Definitions 314

Causes of Recurrent Miscarriage 314

Investigation and Treatment of Recurrent Miscarriage 316

Termination of Pregnancy 317

First Trimester Termination of Pregnancy 317

Second Trimester Termination of Pregnancy 319

Complications of Termination of Pregnancy 319

Ectopic Pregnancy 320

Aetiology 320

Diagnosis of Tubal Pregnancy 321

Symptoms 321

Diagnosis of Tubal Pregnancy 321

Sites of Implantation 323

Rupture of the Tube 323

Rupture into Lumen of Tube 323

Treatment of Tubal Pregnancy 324

Methotrexate 324

Salpingectomy 324

Salpingostomy 324

Conservative 324

Gestational Trophoblastic Disease 325

Pathology 326

Presentation and Genetics 327

Treatment 328

Gestational Trophoblastic Neoplasia 328

Chemotherapy for Choriocarcinoma 330

Miscarriage

Miscarriage occurs in 10–20% of clinical pregnancies, and in the UK it is defined as a pregnancy loss before the 24th week of gestation. In Australia, miscarriage is a pregnancy that spontaneously ends before 20 weeks. After the 20th week of pregnancy, the loss of a fetus is called a stillbirth.

Threatened miscarriage

Technically this refers only to bleeding from the placental site, which is not yet severe enough to terminate the pregnancy. Usually the bleeding is slight and the cervix remains closed. The pregnancy is likely to remain viable.

Inevitable miscarriage

Clinically, the amount of bleeding is variable but the cervix is open. On ultrasound examination, the bleeding is retroplacental and often, fetal heart activity is absent.

Complete miscarriage

A miscarriage in which the fetus, membranes and chorionic tissue are completely expelled from the uterus is termed a complete miscarriage.

Incomplete miscarriage

A miscarriage in which the fetus or membranes or chorionic tissue are incompletely expelled from the uterus. An ultrasound will show debris (retained products of conception) within the uterine cavity.

Missed miscarriage

It is defined as the retention of a non-viable fetus for several weeks without any clinical symptoms.

Other terms

The term early fetal demise is now used to describe what used to be known as an anembryonic pregnancy or a blighted ovum and denotes pregnancies in which a gestational sac is present without the development of a fetal pole.

Management

The method of management of miscarriage depends upon the gestation of miscarriage and clinical facilities available. Apart from expectant management, these methods are identical to those performed during an elective termination of pregnancy.

Early pregnancy loss (≤12Weeks’ Gestation)

Surgical

Clinical indications for surgical evacuation include: persistent excessive bleeding, haemodynamic instability, evidence of infected retained tissue, suspected gestational trophoblastic disease and patient choice. Surgical uterine evacuation for a miscarriage should be performed using a suction curettage. Where infection is suspected, delaying surgical intervention for 12 h is recommended to allow intravenous antibiotic administration.

Preoperative cervical preparation essentially softens the cervix making it easier to dilate and, in doing so, minimises force of dilatation required, haemorrhage and uterine/cervical trauma. The cervix can be prepared using:

– gemeprost (prostaglandin E₁) given as a vaginal pessary 3 h before surgery

– misoprostol (a prostaglandin analogue) given vaginally 3 h before surgery

– mifepristone (an antiprogesterone) given orally at least 12 h before surgery

– laminaria tents inserted into the external cervical os.

Surgical Evacuation of the Products of Conception

Curettage

The patient is anaesthetised and the cervix is dilated. Once dilatation is sufficient, vacuum aspiration of the uterine contents is carried out.

A plastic suction curette is commonly used and is less likely to damage the uterus than metal instruments. Plastic curettes are available in diameters from 4 to 12 mm. The cervix is conventionally dilated to a diameter that is 2 mm less than the gestation age in weeks.

Complications

1. Incomplete uterine evacuation.

2. Uterine perforation and/or damage to abdominal viscera.

3. Sepsis. Broad spectrum antibiotics have been shown to minimise the risk of post-abortal infection.

4. Haemorrhage. Blood loss can be minimised by the use of prostaglandins for preoperative cervical ripening. Bleeding during or after the procedure can be reduced by oxytocic agents such as ergometrine or Syntocinon.

5. Rhesus isoimmunisation. Anti-D should be administered to all rhesus negative women.

Further tissue can be removed with a sponge forcep or a curette. The concave side of the curette loop is pressed against the uterine wall and pulled down. A ‘clean’ uterine wall gives a characteristic sensation to the operating hand.

Reported serious complications of surgery include perforation of the uterus, cervical tears, intra-abdominal trauma, intrauterine adhesions and haemorrhage.

Medical

Medical methods are an effective alternative in the management of a confirmed first-trimester miscarriage. Various medical methods have been described which use prostaglandin analogues (gemeprost or misoprostol) with or without antiprogesterone priming (mifepristone). Protocols should be developed locally with appropriate selection criteria, therapeutic regimens and arrangements for follow-up. To avoid unnecessary anxiety, women should be informed that bleeding may continue for up to 3 weeks after medical uterine evacuation.

Expectant

Expectant management is a method that can be offered in cases of confirmed first trimester miscarriage. Patient counselling is particularly important for those women with an intact sac who wish to adopt an expectant approach. They should be aware that complete resolution may take several weeks. Expectant management for incomplete miscarriage is highly effective. Occasionally, the passage of tissue may be associated with heavy bleeding.

Medical and expectant management should only be offered in units where women have access to 24-h telephone advice and emergency admission, if required.

Anti-D Immunoglobulin

Non-sensitised rhesus (Rh) negative women should receive anti-D immunoglobulin in the following situations: ectopic pregnancy, all miscarriages over 12 weeks of gestation (including threatened) and all miscarriages where the uterus has been evacuated (whether medially or surgically).

Anti-D immunoglobulin is not required threatened miscarriages under 12 weeks of gestation unless the bleeding is heavy or is associated with significant pain. It is not required in cases of complete miscarriage under 12 weeks’ gestation and when there has been no formal intervention to evacuate the uterus.

Late pregnancy loss (>12Weeks’ Gestation)

Surgical

Surgical uterine evacuation remains an option for some women. Dilatation and suction curettage is commonly performed up to 14 weeks’ gestation. Beyond this point, dilatation and evacuation (D & E) can be carried out which involves cervical dilatation to a maximum diameter and the removal of intrauterine contents, usually following a destructive procedure. This procedure is not commonly performed in the UK.

Medical

Again, medical methods are effective in the management of a second trimester miscarriage. As in the case of first trimester loss, there are various medical regimens that have been described using prostaglandin analogues (gemeprost or misoprostol) with or without antiprogesterone priming (mifepristone). Again, local protocols should be developed appropriately with selection criteria, therapeutic regimens and arrangements for follow-up.

In cases where antiprogesterones and vaginal prostaglandins are not available, PGE2 can be very slowly instilled into the cervix through a Foley catheter to facilitate cervical ripening.

Recurrent miscarriage

Introduction and definitions

Recurrent miscarriage, defined as the loss of three or more pregnancies, is a distressing problem that affects up to 1% of women. Recurrent miscarriage is a heterogeneous condition that has many possible causes; more than one contributory factor may underlie the recurrent pregnancy losses.

Causes of recurrent miscarriage

Maternal Age

This is an independent risk factor. Advanced maternal age adversely affects ovarian function, giving rise to a decline in the number of good quality oocytes and resulting in chromosomally abnormal conceptions that rarely develop further.

Previous Number of Miscarriages

This is an independent risk factor in so far as the more miscarriages an individual has had, the more likely she is to have another one.

Genetic Factors

In approximately 3–5% of couples with recurrent miscarriage, one of the partners carries a balanced structural chromosomal anomaly. These are most commonly balanced reciprocal or Robertsonian translocations.

Abnormalities in the Embryo

Recurrent pregnancy loss may be owing to an abnormal embryo which is incompatible with life. As the number of miscarriages increases, the presence of a chromosomal abnormality decreases and the chance of a recurring maternal cause increases.

Uterine Abnormalities

It is difficult to assess the exact contribution that congenital uterine anomalies make to recurrent miscarriage. The estimates of the number of women with recurrent miscarriage, who also have uterine abnormalities, range from 2% to 37%. Women who have serious anatomical abnormalities and have not had treatment for them seem to be more likely to miscarry or give birth early. Minor variations in the structure of the womb generally do not cause miscarriage

Cervical Weakness

The diagnosis of cervical weakness (previously known as incompetence) is usually based on a history of late miscarriage, preceded by spontaneous rupture of membranes or a painless cervical dilatation. This is often over diagnosed as there is currently no satisfactory, objective test that can identify women with cervical weakness in the non-pregnant state.

Endocrine Factors

Maternal diabetes and thyroid disease

Systemic endocrine disorders have been associated with miscarriage. However, they do not cause recurrent miscarriages as long as they are treated and well controlled.

Hyperprolactinaemia

There is insufficient evidence to assess the effect of hyperprolactinaemia as a risk factor for recurrent miscarriage.

Polycystic ovarian syndrome (PCOS)

The characteristic features of this condition are polycystic ovaries associated with an imbalance of hormones. Approximately 50% of women with recurrent early miscarriages have polycystic ovaries (almost double the number of women in the general population). The link between PCOS and recurrent miscarriage is not clear. Many women with PCOS and recurrent miscarriage have elevated levels of luteinising hormone (LH) in their blood. However, reducing the level of LH prior to pregnancy has not been shown to improve the chances of a successful birth.

Thrombophilias

Inherited thrombophilic defects including activated protein C resistance (most commonly owing to factor V Leidin gene mutation), deficiencies of protein C and S and antithrombin III, hyperhomocysteinaemia and prothrombin gene mutations are established causes of systemic thrombosis. Studies have established an association between inherited thrombophilias and fetal loss and late pregnancy complications, with the presumed mechanism being thrombosis of the uteroplacental circulation. Women with recurrent miscarriage who carry the factor V Leidin (FVL) mutation are at a significantly increased risk of miscarriage compared to those with a normal factor V genotype. However, carriage of the FVL mutation did not preclude an uncomplicated pregnancy that could be delivered at term. There is currently no test that can reliably discriminate those women with recurrent miscarriage and the FVL mutation who are destined to miscarry from those who are destined to have a successful pregnancy.

Autoimmune Factors

Approximately 15% of women who have recurrent miscarriages have the antiphospholipid syndrome. This syndrome is characterised by some or all of the following: recurrent miscarriage, thrombosis, thrombocytopenia, poor obstetric history. Anticardiolipin antibodies and lupus anticoagulant levels are also often abnormal.

Infections

Any serious systemic infection can potentially lead to a miscarriage. The presence of bacterial vaginosis in the first trimester of pregnancy has been reported as a risk factor for second trimester miscarriage and preterm delivery but the evidence for its association with first trimester miscarriage is inconsistent.

Environmental Factors

Smoking and alcohol may play a role.

Investigation and treatment of recurrent miscarriage

Even after careful investigation, the majority of women have no obvious cause for recurrent miscarriage. Notwithstanding, the prognosis is generally good, with a mean probability of a live birth in the next pregnancy being around 70%.

1. Genetic factors

Essentially no treatment is available.

2. Uterine abnormalities

All women with recurrent miscarriage should have a pelvic ultrasound to assess uterine anatomy and morphology. Uterine surgery may correct the abnormality, but may not necessarily improve the prognosis. Ironically, these procedures may cause intrauterine adhesions and, thus, reduce fertility.

3. Cervical weakness

The diagnosis is based on a history of mid-trimester miscarriage preceded by a spontaneous rupture of the membranes or a painless cervical dilatation. A transvaginal ultrasound assessment of the cervix during pregnancy may be useful in predicting preterm birth in some cases of suspected cervical weakness. Cervical cerclage is associated with potential hazards that are related to the surgery and the risk of stimulating uterine contractions and, hence, should only be considered in women who are likely to benefit.

4. Endocrine problems

The aim is to obtain optimal control of the condition.

5. Immunological factors

In women with the anticardiolipin antibody syndrome, treatment with low dose aspirin and heparin has been shown to improve the outcome of future pregnancies.

6. Thrombophilias

If protein C and protein S deficiency are found, thromboprophylaxis should be considered. A few well-conducted trials exist for the treatment of these conditions, although there is a rationale for low dose aspirin therapy.

7. Environmental factors

All women wishing to become pregnant should be advised to stop smoking and to minimise their alcohol intake.

Termination of pregnancy

Some people elect to terminate their pregnancy for various reasons which must fall within the Indications for Therapeutic Abortion under the Abortion Act (1967, UK) which was amended 1992. These include:

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 the existing child(ren) of the family of the pregnant woman.

5. …there is substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously handicapped.

To facilitate this process, a certificate of opinion is given by two medical practitioners prior to commencement of the termination process to which it refers.

A single practitioner may give an emergency certificate before termination or, where not reasonably practical, within 24 h of termination, and terminate a pregnancy if it is necessary to save the life of the pregnant woman or to prevent grave permanent injury to her physical or mental health.

First trimester termination of pregnancy

In the first trimester of pregnancy termination can be carried out by surgical or medical methods.

1. Surgical termination of pregnancy (Stop)

This is usually performed up to 14 weeks’ gestation. It involves preoperative cervical ripening with prostaglandin agents preceded by the administration of an antiprogesterone, and (mifepristone) followed by dilatation of the cervix and suction curettage of the products of conception. The methods are almost identical to those already described for the surgical management of a miscarriage.

2. Medical termination of pregnancy

Mifepristone is an antiprogestogen which offers a medical alternative to vacuum aspiration of an early pregnancy and can be used up to 63 days from the first day of the LMP or as dated by an ultrasound. The use of mifepristone is strictly controlled to approved NHS hospitals and premises that have been approved under the Abortion Act. Mifepristone is contraindicated in a suspected ectopic pregnancy, in smokers over 35 years of age, in chronic adrenal failure, porphyria, corticosteroid therapy, coagulation disorders and in women on anticoagulant therapy.

200 mg mifepristone is taken orally and the patient is admitted 36–48 h later for a vaginal administration of prostaglandins (in certain situations prostaglandins can be also given orally). Over 95% of pregnancies are completely aborted. In a small number of cases, surgical evacuation of uterus may be required for any retained products of conception. Side effects include abdominal pain with up to 20% of the patients requiring opiate analgesia following prostaglandin administration. Blood loss is similar to that following surgical termination of pregnancy at the same gestation.

Second trimester termination of pregnancy

1. Surgical termination – dilatation and evacuation (D&E)

Dilatation and evacuation (D & E) involves cervical dilatation to a maximum diameter of 20 mm and removal of the intrauterine contents. This is not commonly performed in the UK.

2. Medical termination

Again mifepristone and prostaglandins are used to facilitate the process, in accordance with the local protocols. The use of mifepristone significantly reduces the interval from induction (prostaglandin administration) to abortion, and so, the vast majority of patients abort within 24 h. Curettage for retained products of conception may be required in up to 30% of patients undergoing a second trimester abortion using medical methods.

3. Extra-amniotic termination

This method may be used if the mifepristone and prostaglandin pessaries are unavailable.

PGE2 is very slowly instilled into the cervix through a Foley catheter.

Complications of termination of pregnancy

Immediate

Major complications occur in approximately 2% of the cases and include haemorrhage, thromboembolism, operative trauma and infection. Minor complications (10%) include lower abdominal pain, bleeding and pelvic infection.

Late

Infertility can occur if a termination is complicated by infection as this increases the risk of tubal occlusion. In general, if women are screened and treated for genital tract pathogens prior to an evacuation procedure, the risk of postoperative infection is significantly reduced. However in the absence of infection, results from several well-designed studies have shown no adverse effects on a future pregnancy from a single uterine evacuation procedure.

Rhesus isoimmunisation can be minimised by administering anti-D to rhesus negative women.

Ectopic pregnancy

The term ‘ectopic’ comes from the Greek ‘ektopis’ meaning ‘displacement’ (‘ek’, out of + ‘topos’, place = out of place). An ectopic pregnancy is an extrauterine pregnancy. This occurs with an incidence of approximately 11.1 per 1000 pregnancies. It is still a cause of maternal death with 10 deaths being reported in the UK between 2002 and 2005.

An ectopic pregnancy is usually caused by various conditions that block or slow the movement of a fertilised egg through the fallopian tube to the uterus.

The trophoblast can successfully implant on any tissue that has an adequate blood supply. The most common site for an ectopic pregnancy is within the fallopian tube. Other less common sites include the cervix, ovary, liver, spleen, stomach and the intestine.

Diagnosis of tubal pregnancy

Tubal pregnancy can present in many ways and misdiagnosis can occur. Many patients now present with mild symptoms as methods of investigation that detect early pregnancy problems such as ectopics, can do so earlier than previously. However, acute ruptures with significant patient compromise still occur.

Symptoms

Pain

Pain in the lower abdomen is always present in the acute presentation. Described as either stabbing or cramp-like, it may be referred to the shoulder if blood tracks to the diaphragm and stimulates the phrenic nerve, and may be so severe as to cause fainting.

Vaginal Bleeding

In about 75% of the cases, a tubal pregnancy presents with vaginal bleeding.

Fainting/Collapse

These pregnancies will cause pain and fainting, leading to anaemia.

If haemorrhage is severe the usual signs of collapse and shock will appear.

Signs

Abdominal Tenderness

Tenderness may be elicited on the left, right or across the lower abdomen.

Pelvic Tenderness

Care should be taken when examining the patient to make sure that an ectopic pregnancy is not ruptured during the process.

Adnexal Mass

Gentle bimanual palpation may reveal a pelvic adnexal mass.

Diagnosis of tubal pregnancy

1. Serum hCG tracking can aid in its diagnosis. An ongoing intrauterine pregnancy should have a doubling (minimum of 2/3) of serum beta hCG in 48 h. A non-continuing pregnancy will usually show a fall in beta hCG. An ectopic pregnancy will show a suboptimal rise, static value or a decline.

2. Ultrasound Features of ectopic pregnancy include:

– absence of a gestation sac within the uterine cavity

– presence of a gestation sac outside the uterus (usually in the adnexal regions)

– demonstration of a live embryo with fetal heart activity outside the uterus.

– free fluid or blood in the adjacent parts of the pelvis.

A transvaginal ultrasound is the diagnostic modality used. In general, ultrasound findings in association with serum beta hCG tracking can help establish the diagnosis of an ectopic pregnancy. In general, there is a serum hCG level at which it is assumed that all viable intrauterine pregnancies will be visualised by a transvaginal ultrasound. This is referred to as the discriminatory zone. When serum hCG levels are below the discriminatory zone (<1000 iu) and there is no pregnancy (intra- or extrauterine) visible on transvaginal ultrasound scan, the pregnancy can be described as being of unknown location.

Sites of implantation

Sites of Implantation

The tubal ampulla is the commonest location followed by the isthmus, but the developing ovum can implant anywhere inside or outside the uterus.

Ampullary implantation: note the thinning of the tube wall.

Cornual implantation is not common but is very dangerous because its rupture is accompanied by bleeding from uterine arteries.

Rupture of the tube

The muscle wall of the tube does not have the capacity of uterine muscle for hypertrophy and its distension and a tubal pregnancy nearly always end in its rupture and the death of the ovum.

Rupture into lumen of tube

Tubal Abortion

This is usual in an ampullary pregnancy at about 8 weeks. The conceptus is extruded, complete or incomplete, towards the fimbriated end of the tube.

Rupture into the Peritoneal Cavity

This usually occurs spontaneously, and often from the narrow isthmus before 8 weeks, or from the interstitial portion at 12 weeks. Haemorrhage is likely to be severe.

Treatment of tubal pregnancy

Patients presenting with collapse and shock with a positive pregnancy test must be assessed and managed like any other critically ill patient. Intravenous access with appropriate blood tests including a full blood count, a coagulation screen and an emergency blood cross match should be established. Fluid resuscitation and an emergency theatre should be organised to deal with the bleeding. In such cases, all procedures are performed as traditional open operations.

If the patient is stable, then management can be medical (using methotrexate intramuscular injection) or surgical.

Methotrexate

Most ectopics follow a chronic course and are confidently diagnosed with ultrasound and βHCG. To avoid surgical intervention, women can be offered this treatment if the βHCG is <3000 and there are no symptoms of rupture. If βHCG levels do not fall, then, 14% may need a further injection and only <10%, in this group, will eventually need surgery if the treatment fails or if the ectopic shows signs of rupture during treatment. The dose is usually 50 mg/m² body surface area.

Salpingectomy

This can be performed following the diagnosis at surgery. Before removing the tube, the other fallopian tube should be examined, because if it is abnormal, then a more conservative surgical approach may have to be adopted. Laparoscopic salpingectomy is the preferred method.

Salpingostomy

This is a conservative approach to the surgical management of ectopics. An incision is made over the antimesenteric border of the tube, the ectopic is removed and the tube left to heal once haemostasis is achieved. There is a risk of a persistent trophoblast that may need to be treated, so follow up βHCG values should be checked. There is also an increased risk of a recurrent ectopic pregnancy.

Conservative

If there is a raised βHCG of <1000 with no further increase in the βHCG levels and no intra-uterine pregnancy on an ultrasound scan, then the pregnancy can be described as being of unknown location. Such cases can be treated conservatively as up to 70% will resolve by themselves. Surgery or medical therapy will be required in some cases.

Gestational trophoblastic disease

Hydatidiform Mole

The incidence of molar pregnancies in Europe and North America is approximately 0.2–1.5 per 1000 live births but there may be a higher incidence in Africa and Asia.

Complete and partial are two distinct forms of a molar pregnancy. The gross specimen from a complete molar pregnancy shows diffuse hydropic placental villi. On scanning, this gives a multicystic appearance to the uterine contents. A partial molar pregnancy can have a similar appearance but the findings can be variable and subtle.

Table 15.1 Features of Partial and Complete Hydatidiform Moles

Feature	Partial mole	Complete mole
Karyotype	Most commonly	Most commonly
	69, XXX or –, XXY	46, XX or –, XY
Pathology
Fetus	Often present	Absent
Amnion, fetal RBC	Usually present	Absent
Villous edema	Variable, focal	Diffuse
Trophoblastic proliferation	Focal, slight–moderate	Diffuse, slight–severe
Clinical presentation
Diagnosis	Missed miscarriage	Molar gestation
Uterine size	Small for dates	50% large for dates
Theca lutein cysts	Rare	25–30%
Medical complications	Rare	10–25%
Post-molar GTN	2.5–7.5%	6.8–20%

RBC, red blood cells; GTN, gestational trophoblastic neoplasia.

(From DISAIA Clinical Gynecologic Oncology 7E Mosby 2007)

Gestational trophoblastic disease – pathology

Premalignant

Complete Hydatidiform Mole

In a complete hydatidiform mole, the villi are grossly swollen and are likened to ‘bunches of grapes’. There is no embryo. Microscopically, the villi are enormously distended. Hyperplasia of both the syncytio-trophoblast and the cytotrophoblast can be observed.

Partial Mole

In this case, there are two populations of villi. Some are of normal size and configuration, and contain fetal vessels, while others show the typical grape-like appearance of hydatidiform change. Frequently, an embryo or embryonic tissue is present. Trophoblast hyperplasia is very focal and is usually confined to the syncytio-trophoblast.

Gestational trophoblastic disease – presentation and genetics

Cytogenetics

Genetics of hydatidiform mole

1. Complete Mole

The karyotype of a complete mole is 46XX in 95% and 46XY in 5%, but all of the chromosomes are of paternal origin. The pronucleus of the ovum is absent. The empty egg is fertilised by a haploid 23X sperm which duplicates its chromosomes without cell division (less commonly) or by two different sperm. Why the ovum should fail to contribute to the process is not known. As complete moles are more likely to become malignant, the karyotype of every mole should be determined.

2. Partial Mole

In a partial mole, fetal tissue of some type is present and the karyotype is entirely different. It is usually triploid – 69XXX or 69XXY with both maternal and paternal DNA. This is due to fertilisation of the egg by two sperm. Partial moles are less likely to undergo malignant change.

Gestational trophoblastic disease – treatment

The diagnosis is made using an ultrasound (see p. 326) and βHCG levels. Partial moles may appear as a missed miscarriage and may not detected until the pathology is available. If a molar pregnancy is suspected, then uterine evacuation should be performed.

Prior to Evacuation

A full blood count, clotting studies and crossmatching for blood type should be performed.

Renal and liver function analysis.

Evacuation

No cervical ripening agents to be used, for example misoprostol.

There is increased incidence of post-evacuation neoplasia.

Suction evacuation using a large suction cannula should be performed.

Post Evacuation

Registration with a gestational trophoblastic disease centre should be done.

Serial βHCG estimation should be performed.

Advise use of reliable contraceptive during follow-up.

Advise not to attempt pregnancy for at least 6 months following treatment.

βHCG levels to be checked after any subsequent pregnancy.

Post-Molar Gestational Trophoblastic Neoplasia

7.5–20% incidence following complete molar pregnancy

2.5–7.5% incidence following partial molar pregnancy.

Chemotherapy is indicated where there is persistent post-molar disease.

Gestational trophoblastic neoplasia

Malignant

Invasive mole

This is a condition in which the molar tissue invades through the decidua and into the myometrium and its associated blood vessels. It almost always results from a complete, rather than a partial, mole. Perforation of the uterus may occur, resulting in invasion of the parametrium.

Spontaneous resolution can occur, but to prevent morbidity and mortality these lesions are treated with surgery where fertility is of no concern and with chemotherapy if fertility sparing is required.

Gestational Choriocarcinoma

This occurs most commonly after a complete molar pregnancy but can also occur after any pregnancy. This is a rare condition and a non-gestational variant can arise directly in the ovary. Only about 2% of moles give rise to a choriocarcinoma but the risk is 1000 times greater than the risk after normal delivery.

These tumours metastasise, with the lung being the commonest site.

Placental Site Trophoblast Tumour

This is a rare lesion in which a few villi are formed. The bulk of the tissue consists of the chorionic epithelium, much of which has not properly differentiated into the usual two types. These can occur at variable lengths of time after pregnancy.

Chemotherapy for choriocarcinoma

A choriocarcinoma is very chemosensitive and its rates of cure can be high. Prognostic variables which help determine a suitable chemotherapeutic regimen are calculated following patient referral to a specialist centre.

Patients in the Low Risk Group

They are treated using a single agent chemotherapy regimen.

Recurrence rates <5%

Patients in High Risk Group

They are treated with multiagent chemotherapy regimen.

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