AFP is a glycoprotein that is synthesized in the fetal liver (primarily), umbilical vesicles and the gut. It is found in elevated quantities in the fetal serum and peaks at around 14 week of gestation.

Vitamin B1 deficiency can lead to Wernicke’s encephalopathy. Alcoholics are at particular risk. In obstetrics all women with hyperemesis gravidarum should receive thiamine supplementation to prevent Wernicke’s.

The internal anal sphincter is innervated by the splanchnic nerves. Sympathetic nerve supply from the inferior hypogastric plexus (for contraction) and parasympathetic supply from nervi erigentes (for relaxation).

The rectus sheath is formed by the aponeurosis of the internal and external oblique muscles and the transversus abdominus muscle. The internal oblique divides into two lamellae and encloses the rectus muscle. Anteriorly it fuses with the aponeurosis of the external oblique and posteriorly with that of the transverus abdominus. Below the arcuate line the aponeurosis of all the flat muscles lies anteriorly and posteriorly it is only enclosed by the transveralis fascia.

Repair the vaginal mucosa using rapidly absorbed suture material on a large, round body needle. Start above the apex of the cut or tear (as severed vessels retract slightly) and use a continuous stitch to close the vaginal mucosa.

The levels of evidence range from I-IV:
1a: Systematic reviews (with homogeneity) or metanalysis of randomized controlled trials: highest level of evidence.
1b: Individual randomized controlled trial (with narrow confidence interval)
1c: All or none randomized controlled trials
2a: Systematic reviews (with homogeneity) of cohort studies
2b: Individual cohort study or low quality randomized controlled trials (e.g. <80% follow-up)
2c: Outcomes Research; ecological studies
3a: Systematic review (with homogeneity) of case-control studies
3b: Individual case-control study
4: Case series (and poor quality cohort and case-control studies)
5: Expert opinion without explicit critical appraisal, or based on physiology, bench research or first principles.

Liver cirrhosis is known to lead to decreased levels of SHBG. Other causes of high SHBG are:
Oestrogens e.g. oral contraceptives
Pregnancy
Hyperthyroidism
Liver cirrhosis
Anorexia nervosa
Drugs e.g. anticonvulsants

History of heavy menstrual bleeding and amenorrhoea favour the diagnosis of a fibroid uterus. All the given responses are causes for subfertility. Ectopic pregnancy presents with abdominal pain has an acute presentation. Endometriosis and adenomyosis usually don’t present with amenorrhoea or heavy bleeding respectively. PID presents with chronic pelvic pain and is not related to menstruation.

Oral progestogen therapy for 21 days (day 5-26) is considered effective but is only a short-term therapy for menorrhagia. Myomectomy should only be considered if the woman would like to conceive later on. Due to the recurrent nature of fibroids, it is likely that the woman would need more surgeries in the future, which is not ideal. Furthermore, if there is a large number of fibroids or the size of the fibroids are large, myomectomy would not be an option for reasons such as the feasibility. If myomectomy for multiple fibroids prove to be unsuccessful, the ultimate outcome would still have to be a hysterectomy.

In cases where there is significant enlargement of the uterus, endometrial ablation would be difficult and the long-term cure rate of symptoms would be considerably low. The best next step would be a total abdominal hysterectomy since it would solve her menorrhagia and within a few years’ time, she would be expected to attain menopause anyway. Ponstan or mefenamic acid has been found to be superior to tranexamic acid for menorrhagia. However, it can still prove to be ineffective in some cases and also not a long term solution.

Any new onset of hypertension associated with proteinuria after 20 weeks of gestation in a previously­ normotensive woman is referred to as Preeclampsia.
Most commonly found risk factors for pre-eclampsia are:
– Preeclampsia in a previous pregnancy
– Family history of preeclampsia
– a prior pregnancy with poor outcome like placental abruption, IUGR, fetal death in utero, etc
– An interdelivery interval greater than 10 years
– Nulliparity, increases risk by 8 times
– Pre-existing chronic medical conditions or chronic hypertension
– pre-existing or gestational Diabetes
– chronic Renal disease
– Thrombophilias g. protein C and S deficiency, antithrombin Ill deficiency, or Factor V Leiden mutation
– Antiphospholipid syndrome
– Systemic lupus erythematous
– Maternal age greater than or equal to 40 years
– Body Mass Index (BMI) greater than 30 kg/m2
– Multiple pregnancy
– Raised blood pressure at booking
– Gestational trophoblastic disease
– Fetal triploidy

Maternal age between 18 and 40 years is found to be associated with a decreased risk for developing preeclampsia, and not an increased risk.
NOTE– Previously, age 16 years or younger was thought to be a risk factor for developing preeclampsia; however, recent studies conducted had failed to establish any meaningful relationship between the two.

The nutritional status of a woman before and during pregnancy is important for a healthy pregnancy outcome. Pregnancy is a state of increased requirement of macro and micronutrients, and malnourishment or inadequate dietary intake before and during pregnancy, can lead to adverse perinatal outcomes. Many nutritional interventions have been proposed for pregnant mothers. These include multiple micronutrients (MMN), iron/folate, balanced protein energy, calcium, zinc and folic acid supplementation.

Varicella is a live vaccine. The recent RCOG green top guidelines suggest vaccine can be considered postpartum or pre pregnancy but NOT whilst pregnant. In the non-immune pregnant woman they should be advised to avoid contact with people with chickenpox or shingles and to contact a healthcare professional promptly if exposed. If they have a significant exposure VZIG should be offered as soon as possible.

Small teeth with faulty enamel is more associated with fetal alcohol syndrome (FAS).

In FAS, the most common orofacial changes are small eyelid fissures , flat facies, maxillary hypoplasia, short nose, long and hypoplastic nasal filter, and thin upper lip. The unique facial appearance of FAS patients is the result of changes in 4 areas: short palpebral fissures, flat nasal bridge with an upturned nasal tip, hypoplastic philtrum with a thin upper vermillion border, and a flat midface. Other facial anomalies include micrognathia, occasional cleft lip and/or palate and small teeth with defective enamel.

Intrahepatic cholestasis characterized by reversible cholestasis typically occurring in the second or third trimester of pregnancy, elevated serum aminotransferases and bile acid level and resolution of symptoms by 2 to 3 weeks after delivery. Ursodeoxycholic acid has shown to reduce the symptoms of this condition.

This patient should be advised to use both an OCP and a condom. The combined oestrogen/progestogen contraceptive pill (COCP) has been found to be very effective. However, she should be made aware that it would not provide any protection from any sexually transmitted diseases so she might still be at risk of developing a STD, depending on her sexual partner preferences. To ensure protection from STDs, she should be advised to use both condoms as well as the combined OCP. An IUCD (intrauterine contraceptive device) would not be preferable if she has multiple sexual partners (high risk of STDs). If she has been screened for STDs, does not actively have an STD and has only one sexual partner then IUCD is a possible option. Some issues that may arise with spermicide use could be related to compliance. This also applies to using condoms alone. These two options are less reliable as compared to COCP.

When cervical biopsy or colposcopy doesn’t explain the severity of the pap smear results cone biopsy is done. In 10% of biopsies, results will be different from that of the pap smear as in this patient with pap smear showing HSIL and colposcopy showing chronic cervicitis.

In such cases conization is indicated. Repeating the pap smear could risk prompt management of a serious problem. No destructive procedure, ablation or cryotherapy, should be done before diagnosis is certain.

Nausea and vomiting experienced in 80% of pregnancies Hyperemesis gravidarum (HG) is an extreme form of nausea and vomiting which affects around 1.5% of women. Caused by high levels HCG. Definitions vary but most consider it to be defined by severe nausea and vomiting associated with weight loss greater than 5% of pre-pregnancy weight with metabolic disturbance (typically dehydration and/or ketosis).

It is important to be aware of which ant-epileptics induce cytochrome P450. Of the above Topiramate and Phenytoin are moderate and strong inducers respectively.

Progesterone down regulates gastric motility meaning drugs are absorbed and metabolised more slowly, thus drugs are absorbed, metabolised and cleared more slowly. Most of the drugs are transported after binding to the albumin.
Lower albumin levels mean a greater unbound drug fraction but as this may be thought to increase drug concentrations it actually leaves more available for hepatic clearance or renal excretion so overall drug concentrations are unchanged and metabolism increased.
Increase in hepatic flow will increase the metabolism of the drug as the drug will be transported faster.
Increased renal blood flow will result in the faster clearance of the drug from the body.

Abnormal placental adherence to the uterus, generally termed Placenta Accreta, is divided into 3 conditions.
– Placenta accreta: refers to the invasion of the chorionic villi beyond the decidual surface of the myometrium.
– Placenta increta: the villi invade deep into the myometrium but spare the serosa;
– Placenta percreta: the chorionic villi invade through the myometrium, penetrate the uterine serosa, and may invade surrounding pelvic structures.

These conditions can predispose patients to obstetric bleeding in the third trimester, often requiring emergency intervention.

Risk factors in the development of an abnormal placental adherence include previous c-sections. Placenta Previa, is also a cause of antepartum haemorrhage and serves as a risk factor in the development of abnormal placental adherence.

Venous thromboembolic disease (VTE) is the most common cause of direct maternal death in the UK. In the most recent triennium, there were 41 fatalities, giving a maternal mortality rate of 1.94 per 100 000 – more than twice that of the next most common cause, pre-eclampsia. As pregnancy is a hyper coagulable state. There are alterations in the fibrinolytics and thrombotic pathways. There is also an increased production of clotting factors during pregnancy.

Medical abortion is preferred from 4 to 9 weeks of gestation and in Australia, suction curettage is the most frequently used method of abortion as it is considered useful from 6 to 14 weeks of gestation.

Mifepristone is a synthetic anti-progesterone, which is found to be effective for abortion when combined with misoprostol. There are evidences which suggest the effectiveness of misoprostol and mifepristone in both first and second trimesters. It is most commonly administered as a single dose of mifepristone followed by misoprostol, a prostaglandin, given orally or vaginally two days later. Prostaglandin can be repeated at an interval of 4 hours if required.
As the vaginal use shows only few gastrointestinal side effects Misoprostol is more effective and better tolerated vaginally than orally. Misoprostol is not approved for its use in termination of pregnancy, but is available in the market due to its indications in other conditions.
Methotrexate can be used orally or as an intramuscular injection followed by misoprostol up to seven days later, but this also is not a preferred method for termination of pregnancy in Australia.

Fetal ultrasound scanning is considered an essential part of routine antenatal care with first trimester scans recommended for confirming viability, accurate estimation of gestational age and determining the number of foetuses. Fetal crown-rump length (CRL) is measured in early pregnancy primarily to determine the gestation age (GA) of a foetus and is most reliable between 9+0 to 13+6 weeks’ gestation, but not beyond.

The ovarian arteries are considered the main blood supply for the ovaries. The ovarian arteries usually arise from the lateral aspect of the abdominal artery, though in some instances they may arise from the renal or iliac arteries.

Fetal production of immunoglobulin begins early on, at about 10 weeks gestation with the production of IgM antibodies. Maternal IgG, which is a key component of fetal immunity, is passed on to the foetus through the placenta from 12 weeks of gestation. Secretory IgA is not produced until after birth.

DNA replication occurs during S phase but that isn’t one of the options. Remember Interphase comprises G1,S and G2 phases!

Primary infertility is defined as the inability to conceive after a year of unprotected, timed sexual intercourse in a nulliparous patient under the age of 35. (After 35 years of age, infertility testing can begin after 6 months.) Because the patient’s partner’s sperm analysis is normal, female factor infertility is the most likely explanation. This patient’s adolescent hospitalizations are likely due to pelvic inflammatory disease (PID), a common cause of infertility caused by tubal scarring and blockage.

A hysterosalpingogram, which includes infusing radiocontrast into the cervix under fluoroscopy, is the first-line imaging technique for determining fallopian tube patency. A hysterosalpingogram is a non-invasive procedure that can detect uterine cavity irregularities (e.g., bicornuate uterus).

Peritoneal adhesions and endometriosis can be seen and treated directly using laparoscopy.

PID-related scarring inside the fallopian tubes can be assessed by laparoscopy with chromotubation; however, it is invasive, expensive, and not utilized first-line.

Ovulation is detected using a mid-cycle LH level. The LH surge can be detected in urine and serum 36 hours before ovulation. Regular menstrual periods are characterized by mittelschmerz (mid-cycle pelvic pain), which indicates ovulation. As a result, an LH level would be useless.

Ovarian reserve begins to deteriorate around the age of 35, and serum FSH levels rise in women who are losing their ability to ovulate. Because this patient is much younger and has regular periods, a drop in ovum quantity is unlikely to be the reason for infertility.

Increased serum androgen levels can prevent ovulation by inhibiting the release of GnRH and FSH through feedback inhibition. The patient has regular cycles and no hyperandrogenic symptoms, despite her sister having polycystic ovarian syndrome (e.g., hirsutism, irregular menses).

In a nulliparous patient under the age of 35, primary infertility is defined as the inability to conceive after a year of unprotected sexual intercourse. A hysterosalpingogram is used to determine the cause of infertility, such as tubal blockage caused by a previous pelvic infection.

CA-125 has found application as a tumour marker or biomarker that may be elevated in the blood of some patients with specific types of cancers, or other conditions that are benign. Increased level of CA125 appears in fifty percent of stage 1 ovarian cancer patients and more than 90% with stages 2-4 ovarian cancer. CA-125 is therefore a useful tool for detecting ovarian cancer after the onset of symptoms as well as monitoring response to treatment and for predicting a patient’s prognosis after treatment.

Human Papillomavirus has been is implicated in the development of genital warts as well as, head and neck, anogenital and cervical cancers, with the most important high-risk strains being 16 and 18. Over 50% of women worldwide are thought to possess antibodies against various strains of HPV after natural infection. Many infections are asymptomatic and are cleared within 2 years. Several vaccines have been formulated against HPV, one of which is Gardasil, a quadrivalent vaccine against HPV types 6,11, 16,18.

Mature cystic teratomas of the ovary are often discovered as incidental findings on physical examination, during radiographic studies, or during abdominal surgery performed for other indications.

Most mature cystic teratomas can be diagnosed at ultrasonography (US) but may have a variety of appearances, characterized by echogenic sebaceous material and calcification.

Follicular cysts are simple fluid-filled cysts and never have calcifications.

Mucinous cystadenoma usually develop in the third to fifth decades of life and typically cause vague symptoms, such as increasing abdominal girth, abdominal or pelvic pain, emesis, fatigue, indigestion, constipation, and urinary incontinence However, calcifications are not usually seen.

Brenner tumour is also a benign epithelial ovarian tumour but it is solid, occurring most often in women over 50 years of age.

Serous cystadenoma also does not show calcifications.

The first sign of puberty in females is the development of breasts.

A fibroid is a benign smooth muscle tumour or Leiomyoma. As such it is something of a misnomer. Leiomyosarcoma and Angioleiomyoma are malignant tumours of smooth muscle under the WHO sort tissue tumour classification Rhabdomyoma is a skeletal muscle tumour Myofibroma is seen in fibromatosis

Endometrial tissue found within the myometrium is Adenomyosis. If endometrial tissue is found at a distant site to the uterus it is termed endometriosis. Fibroids are smooth muscle tumours (Leiomyoma’s) sometimes called myoma’s.

Vesicovaginal fistula (VVF) is a subtype of female urogenital fistula (UGF). VVF is an abnormal fistulous tract extending between the bladder and the vagina that allows the continuous involuntary discharge of urine into the vaginal vault. The uncontrolled leakage of urine into the vagina is the hallmark symptom of patients with UGFs. Patients may complain of urinary incontinence or an increase in vaginal discharge following pelvic surgery or pelvic radiotherapy with or without antecedent surgery. The drainage may be continuous; however, in the presence of a very small UGF, it may be intermittent. Increased postoperative abdominal, pelvic, or flank pain; prolonged ileus; and fever should alert the physician to possible urinoma or urine ascites and mandates expeditious evaluation. Recurrent cystitis or pyelonephritis, abnormal urinary stream, and haematuria also should initiate a workup for UGF.

Urinary trace infection presents with dysuria and urgency.
Detrusor instability causes urge incontinence.
Neurogenic bladder from diabetic neuropathy would also have urgency.

Antenatal screening for rubella IgG is a routine recommended for all pregnant women at their first visit. All pregnant women who have a history of contact with rubella or any clinical features consistent with rubella –like illness should be screened for the presence of rising antibody titre and / or rubella specific IgM. Serological confirmation is mandatory for diagnosing rubella.
As in this case scenario, positive lgM for rubella indicates active rubella infection, in such cases it is recommended to repeat the test. If lgM is still positive, it confirms rubella infection. No further testing from another laboratory is required.
The risk for fetal infection and damage is higher if rubella infection occurs during the first trimester of pregnancy, which is 85% in the first two months of pregnancy and 50 -80% in the third month. Therefore, termination of pregnancy is usually recommended in this situation. NHIG has been used in trials for prophylaxis and prevention of congenital rubella syndrome after contact to a case with rubella infection, but the results have been discouraging, therefore, it is not advisable.
In the given case, rubella infection has been established already, so NHIG will not be of any benefit as primary prevention.
Rubella-containing vaccines like MMR vaccine is a live attenuated vaccine are contraindicated throughout pregnancy, it should be avoided; and women who remain susceptible to rubella should receive MMR vaccine postpartum.
Risk of fetal infection and/or fetal damage or for development of congenital rubella syndrome is related to the timing of maternal infection. Cases with Primary infection is found to be in higher risk
In cases of asymptomatic re-infection with a good history of previous positive serology, even though it is difficult to quantify, the risk of fetal infection has been reported to be < 5 percent. Congenital rubella syndrome following maternal re-infection is considered rare particularly if re-infection occurs after 12 weeks. If the clinical picture is typically of rubella or if possibility of previous immunity is inconclusive based on serology, then the risk is assumed to be the same as that of primary infection.

A Bicornuate uterus (heart shaped) is the result of abnormal fusion and reabsorption of the paramesonephric ducts during embryogenesis. Mullerian agenesis typically results in failure to form a uterus. Mullerian duct fusion abnormalities can cause a bicornuate malformation. PKD-1 gene abnormalities are associated with PCOS. Crossed fused ectopia result in Horseshoe kidney.

OCPs should be started in this patient as well as condoms to prevent likely sexually transmitted infections.

Condoms alone are not effective for prevention of pregnancy.

OCPs alone do not prevent from sexually transmitted infections.

It is not appropriate to inform the parents and the patient hasn’t refused any advice.

Vulvovaginal candidiasis is the most common genital infections and it is caused by candida albicans in 80-92% of the cases. It colonise the vaginal flora in 20% of non pregnant and 40% pregnant women.

X-rays carry low levels of risk during pregnancy and are not a significant cause for concern if the total exposure to ionising radiation is less than 5 rads throughout the pregnancy; a chest X-ray is about 0.00007 rads. The amount of radiation generated from a chest X-ray is equivalent to 2.4 days of natural background radiation. Non-urgent radiological tests should, however, be avoided between 10-17 weeks gestation as there is a higher risk of central nervous system teratogenesis during this time.

During childbearing the vagina and perineum are prone to lacerations that may involve the skin or can extend into the anal sphincter complex. It is important to be able to identify obstetric and anal sphincter injuries to provide adequate care and prevent complications. In the classification of obstetric tears according to RCOG guidelines:

First degree tear: injury to the perineal skin and/or the vaginal mucosa
Second degree tears: Injury to perineum involving perineal muscles but not the anal sphincter.
Third-degree tear: Injury to perineum involving the anal sphincter complex:
Grade 3a tear: Less than 50% of external anal sphincter (EAS) thickness torn.
Grade 3b tear: More than 50% of EAS thickness torn.
Grade 3c tear: Both EAS and internal anal sphincter (IAS) torn.
Fourth-degree tear: Injury to perineum involving the anal sphincter complex (EAS and IAS)
and anorectal mucosa.

Ureters are muscular tubes that run from the kidneys to the urinary bladder. It is lined by transitional epithelium.

When the red cells are coated with immune IgG antibody, the cells do not agglutinate but when anti-IgG antiserum is added to these sensitized cells visible agglutination occurs. This is known as a positive direct coombs test.

There is an association between 20 to 30% increase in the risk for developing pyelonephritis during later pregnancy and untreated cases of bacteriuria in pregnancy. This is due to the physiological changes occurring to urinary tract during pregnancy, it is also found that untreated bacteriuria can be associated with even preterm birth and low birth weight. Risk of symptomatic urinary tract infection (UTI) during pregnancy can be reduced by antibiotic treatment of asymptomatic bacteriuria

The most common pathogen associated with asymptomatic bacteriuria is Escherichia coli, which accounts to more than 80% of isolates and the second most frequently cultured uropathogen is Staphylococcus saprophyticus. Other Gram-positive cocci, like group B streptococci, are less common. Gram-negative bacteria such as Klebsiella, Proteus or other Enterobacteriaceae are the other organisms involved in asymptomatic bacteriuria.

Although the context patient is asymptomatic, her urine dipstick shows positive nitrite and leukocyte, suggestive of urinary tract infection, so oral antibiotics like cephalexin or nitrofurantoin are advisable. Normally a five day course of oral antibiotic will be sufficient for the treatment of uncomplicated UTI or asymptomatic bacteraemia in pregnant women. As the patient is currently at her 38 weeks of gestation nitrofurantoin is contraindicated so it is best to prescribe her with Oral Cephalexin. This is because nitrofurantoin is associated with an increased risk of neonatal jaundice and haemolytic anaemia, so should not be used close to delivery, that is after 37 weeks of gestation or sooner if early delivery is planned.

Acute pyelonephritis should be treated with Intravenous antibiotic treatment, guided by urine culture and sensitivity reports as soon a available. A course of minimum of 10-14 days with IV + oral antibiotics is recommended as treatment for pyelonephritis, along with an increased fluid intake as intravenous fluids in clinically dehydrated patients. Even though urinary alkalisers are safe in pregnancy, prescription of urinary alkalisers alone is not recommended due to its low effectiveness compared to antibiotics, also as it can result in a loss of treatment efficacy urinary alkalisers should never be used in combination with nitrofurantoin.

At any stage of pregnancy, if Streptococcus agalactiae, a group B streptococcus [GBS], is detected in urine the intrapartum prophylaxis for GBS is usually indicated.

Cephalo-pelvic disproportion exists when the capacity of the pelvis is inadequate to allow the foetus to negotiate the birth canal. This may be due to a small pelvis, a nongynecoid pelvic formation, a large foetus, an unfavourable orientation of the foetus, or a combination of these factors. Diagnosis of CPD may be made when there is failure to progress, but not all cases of prolonged labour are the result of CPD. Use of ultrasound to measure the size of the foetus in the womb is controversial, as these methods are often inaccurate and may lead to unnecessary caesarean section; a trial of labour is often recommended even if size of the foetus is estimated to be large.

Domperidone and metoclopramide are D2 dopamine receptor antagonists. They are primarily used to promote gastric motility. They are also known as galactagogues and they promote the production of milk. Cabergoline and bromocriptine are prolactin inhibitors and they reduce milk production.

Prothrombin time is increased in:
– Factor V deficiency
– Vitamin K deficiency (which affects factors 2,7 and 10)
– Warfarin therapy
– Severe liver failure
Protein C is an anticoagulant and deficiency results in a hyper-coagulable state with tendency towards thrombosis.

Threatened miscarriage is a term used to describe any abnormal vaginal bleeding that occurs in first trimester, sometime associated with abdominal cramps. The cervix remains closed and the pregnancy may continue as normal.

Glucagon release is inhibited by increased blood glucose, ketones, free fatty
acids, insulin, raised urea levels and somatostatin. Glucagon is produced by alpha cells of the pancreas and increases the plasma glucose level by stimulating glycogenolysis and gluconeogenesis.

Proteinuria of more than 1+ on dipstick should be investigated to quantify the amount of proteinuria. A protein: creatinine ratio can be used to determine the severity of proteinuria, where levels of more than 30 mg/mmol indicate significant proteinuria.

Premature menopause has been diagnosed biochemically in this patient. Menopause is considered premature when it happens without warning in a woman under the age of 40.
Follicular development is common in ultrasonography investigations of women with primary ovarian failure, but ovulation is rare. So this woman isn’t ovulating.

Exogenous oestrogen treatment in physiologic amounts does not appear to improve the rate of spontaneous ovulation.
Women with primary ovarian failure from any cause may be candidates for donor oocyte in vitro fertilisation (IVF).

Oestrogens, clomiphene citrate, and danazol are examples of treatment approaches that have been shown to be ineffective in patients with premature ovarian failure.