Early Pregnancy Flashcards

1
Q

What is RhD sensitization and why is it important in pregnancy?

A

RhD sensitization occurs when a Rh-negative individual is exposed to Rh-positive blood, leading to the development of antibodies. This can cause complications in future pregnancies, especially if a Rh-negative woman carries a Rh-positive baby, leading to hemolytic disease of the fetus and newborn (HDFN).

In the UK, around 85% of the population are RhD positive. The RHD gene is dominant so one copy from either parent makes pos.

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2
Q

Dose of anti-D

A

The recommended minimum dose for treating fetomaternal hemorrhage (FMH) is 500 IU for up to 4 mL of fetal red cells. Additional doses are based on the volume of fetal cells, calculated at 125 IU per 1 mL of fetal red cells.

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3
Q

When should anti-D immunoglobulin (anti-D Ig) be administered?

A

Anti-D Ig should be given to D-negative pregnant women after events like
1. Sensitising events: miscarriage, trauma, invasive procedures (amniocentesis),
2. At 28 and 34 weeks of pregnancy as routine prophylaxis for non-sensitized D-negative women carrying an Rh-positive fetus,
3. After delivery of a Rh-positive baby ( within 72 hours ).

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4
Q

What is the purpose of anti-D Ig after a sensitizing event or delivery of a Rh-positive baby?

A

Anti-D Ig is used to prevent RhD sensitization by clearing Rh-positive fetal red cells from the maternal circulation, preventing complications in future pregnancies.

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5
Q

What is the safety profile of anti-D Ig?

A

Anti-D Ig is derived from pooled plasma and undergoes safety measures like screening for viruses. Adverse reactions are rare but may include allergic reactions or anaphylaxis, especially in those with IgA antibodies.

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6
Q

What are the available preparations of anti-D Ig in the UK?

A

D-GAM® (IM use only) and Rhophylac® (IM or IV use) are the main preparations available. D-GAM® is not suitable for IV use due to the risk of severe hypersensitivity.

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7
Q

How should anti-D Ig be administered?

A

Anti-D Ig is typically administered intramuscularly (IM) in the deltoid muscle. In women with bleeding disorders, IV or subcutaneous administration may be preferred. Doses are calculated based on FMH testing results.

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8
Q

What should be done if anti-D is detected in a sample from a pregnant woman?

A

The source of anti-D (immune or passive) should be determined. If it is unclear, prophylaxis should continue according to guidelines for D-negative women.

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9
Q

Passive vs Immune Anti-D Detection:

A

After anti-D Ig administration, detectable anti-D may be passive (from the injection) or immune (produced by the body). If anti-D is detected in a pregnant woman at 28 weeks, investigations should determine its origin. If it is unclear, prophylaxis should continue to be administered as per guidelines for D-negative women.

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10
Q

Timeline of Rh testing

A

Early Pregnancy: Blood tests check for blood group and if RhD-negative, additional check for anti-D antibodies

If NO anti-D antibodies: blood is rechecked at 28 weeks, and an anti-D immunoglobulin injection is offered to prevent rhesus disease.

If YES anti-D antibodies: closer monitoring is required. If a Doppler ultrasound shows faster-than-normal blood flow in the baby, foetal blood sampling (FBS) may be performed to check for anaemia.

At Birth: Blood is taken from the baby’s umbilical cord (Coombs test) to check their blood group and for anti-D antibodies.
If the mother has anti-D antibodies, the baby’s blood is tested for iron deficiency anaemia and newborn jaundice.

Future Testing: Routine testing may identify the baby’s RhD status to avoid unnecessary treatment for RhD-negative women without antibodies.

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11
Q

What is hemolytic disease of the fetus and newborn (HDFN)

A

A condition where fetal red blood cells are destroyed due to blood group incompatibility, primarily involving Rh or ABO blood types.

Leading to hemolysis, anemia, and hyperbilirubinemia.

Rh incompatibility usually affects subsequent pregnancies because maternal sensitization occurs during the first pregnancy, leading to more severe complications such as intrauterine hydrops fetalis in later pregnancies.

ABO incompatibility, however, can impact the first pregnancy since maternal antibodies preexist.

Diagnosis can occur before or after birth through laboratory tests and imaging studies, and treatments range from phototherapy and supplementation to transfusions in severe cases.

Most common: Rh-negative mother is sensitized to Rh-positive fetal red blood cells.

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12
Q

What are common clinical manifestations of HDFN?

A

Neonatal jaundice, anemia, hydrops fetalis (in severe cases), hypotonia and kernicterus in untreated cases.

Around 50% of babies diagnosed with rhesus disease have mild symptoms that are easily treatable.

Symptoms can sometimes develop up to 3 months afterwards.

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13
Q

How is HDFN diagnosed antenatally?

A

Maternal tests: ABO and Rh typing, antibody screening, and titer monitoring.

Fetal tests: Ultrasound for hydrops fetalis, Doppler ultrasound of the middle cerebral artery (high flow in anaemia), and amniocentesis for bilirubin levels.

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14
Q

What is the key postnatal test for HDFN?

A

A positive direct antiglobulin (Coombs) test, along with anemia, reticulocytosis, and hyperbilirubinemia in the neonate.

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15
Q

What conditions should be considered in the differential diagnosis of HDFN?

A

Physiologic jaundice, prematurity, G6PD deficiency, thalassemia, sepsis, Gilbert syndrome, hypothyroidism.

Polyhydramnios and placentomegaly from various fetal conditions.

Nonimmune hydrops fetalis from cardiac, chromosomal, or infectious causes

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16
Q

What are some signs suggesting nonimmune hydrops fetalis?

A

Cyanosis unresponsive to oxygen (cardiac disease).

Hypotonia (congenital myopathy or hypothyroidism).

Hepatosplenomegaly with dysmorphism (metabolic storage diseases).

Dermatitis with hepatosplenomegaly (TORCH infections).

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17
Q

What are complications of untreated severe HDFN?

A

Hydrops fetalis.
Kernicterus.
Anemia.
Long-term neurological dysfunction.

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18
Q

Complete molar pregnancy

A

duplication of a single spermatozoa inside an empty ovum (75-80%) or dispermic fertilisation of an empty ovum (20-25%).

They contain two sets of paternal chromosomes with a karyotype of 46 XX (most commonly) or 46 XY.

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19
Q

Partial molar pregnancy

A

dispermic fertilisation of a normal ovum (90%) and contain one set of maternal chromosomes and two sets of paternal chromosomes with a karyotype of 69 XXX (most commonly), 69 XXY or 69 XYY

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20
Q

Molar pregnancy: presentation

A

Irreg PV bleeding
+ve PT
USS features

Less common presentations:
hyperemesis, excessive uterineenlargement, hyperthyroidism, early-onset pre-eclampsia and abdominal distension due totheca lutein cysts.

Very rarely women can present with haemoptysis or seizures due to metastatic diseaseaffecting the lungs or brain.

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21
Q

Molar pregnancy: Can oxytocic infusions be used during surgical removal?

A

The use of oxytocic infusion prior to completion of the removal is not recommended.

If the woman is experiencing significant haemorrhage prior to or during removal, surgical removal should be expedited and the need for oxytocin infusion weighed up against the risk of tissue embolisation

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22
Q

How should women with an elevated human chorionic gonadotrophin after a possible pregnancy event be managed?

A

Referral to a GTD centre should be considered for all women with persistently elevatedhuman chorionic gonadotrophin (hCG) either after an ectopic pregnancy has been excluded, orafter two consecutive treatments with methotrexate for a pregnancy of unknown location.

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23
Q

Which women should be investigated for GTN after a non-molar pregnancy?

A

Any woman who develops persistent vaginal bleeding after a pregnancy event is at risk ofhaving GTN.

A urine hCG test should be performed in all cases of persistent or irregular vaginal bleeding lasting more than 8 weeks after a pregnancy event.

Symptoms from metastatic disease, such as dyspnoea and haemoptysis, or new onset ofseizures or paralysis, can occur very rarely.

Biopsy of secondary deposits in the vagina can cause major haemorrhage and is notrecommended.

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24
Q

What is the optimum follow-up following a diagnosis of GTD?

A

For complete molar pregnancy, if hCG has reverted to normal within 56 days (2 months) of the pregnancy event then follow-up will be for 6 months from the date of uterine removal.

If hCG has not reverted to normal within 56 days of the pregnancy event then follow-up will befor 6 months from normalisation of the hCG level.

Follow-up for partial molar pregnancy is concluded once the hCG has returned to normal on two samples, at least 4 weeks apart.

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25
What is the optimum treatment for GTN?
Women with GTN may be treated with single-agent or multi-agent chemotherapy. Treatment used is based on the FIGO 2000 scoring system for GTN following assessment at the treatment centre. PSTT and ETT are now recognised as variants of GTN. They may be treated with surgerybecause they are less sensitive to chemotherapy.
26
What is the recommended interval between a complete or partial molar pregnancy and trying toconceive in the future?
Women are advised not to conceive until their follow-up is complete. Women who undergo chemotherapy are advised not to conceive for 1 year after completion of treatment, as a precautionary measure.
27
What is the monitoring of women following a successful pregnancy after a previous molar pregnancy?
Women who have a pregnancy following a previous molar pregnancy, which has not required treatment for GTN, do not need to send a post-pregnancy hCG sample. Histological examination of placental tissue from any normal pregnancy, after a molar pregnancy, is not indicated.
28
What is the long-term outcome of women treated for GTN?
Near 100% cure rate Further pregnancies are achieved in approximately 80% of women following treatment for GTN with either methotrexate alone or multi-agent chemotherapy. There is an increased risk of premature menopause for women treated with combination agent chemotherapy. Women, especially those approaching the age of 40 years, should be warned of the potential negative impact on fertility, particularly when treated with high-dose chemotherapy
29
Risk of GTN following molar / partial molar pregnancy?
After surgical evacuation of complete hydatidiform mole, approximately 15–20% of women go on to develop GTN requiring chemotherapy. The risk after partial molar pregnancy is much lower, at around 0.5–1% If human chorionic gonadotrophin (hCG) levels spontaneously revert to normal after uterine evacuation, the risk of post-molar GTN has been reported as only 0.4%
30
Are fertility and pregnancy outcomes affected after GTD?
Fertility rates after hydatidiform mole have been reported to be equivalent to those of the general population. Risk of GTD in subsequent pregnancy is about 1–2%. Fertility is preserved after chemotherapy for GTN in the vast majority. There has been concern that fertility levels may be reduced after chemotherapy for GTN, particularly multi-agent chemotherapy.However, evidence from case series2 suggests that pregnancy outcomes are favourable when compared to the general population, even in women who conceive within 12 months of treatment.
31
Contraception and Molar pregnancy
Hormonal contraception can be started immediately after uterine evacuation for GTD. most methods of contraception can be safely used after treatment for GTD and can be started immediately after uterine evacuation, with the exception of intrauterine contraception (IUC). IUC should not be inserted in women with persistently elevated hCG levels or malignant disease (UKMEC 4) IUC should not normally be inserted until hCG levels have normalised but may be considered on specialist advice with insertion in a specialist setting for women with decreasing hCG levels following discussion with a GTD centre (UKMC 3) Women should be advised that additional contraceptive precautions (e.g. barrier methods/abstinence) are required if hormonal contraception is started 5 days or more after treatment for GTD. Additional contraceptive precaution is not required if contraception is initiated immediately or within 5 days of treatment for GTD.
32
Is emergency contraception (EC) safe to use after GTD?
Emergency contraception (EC) is indicated if unprotected sexual intercourse (UPSI) takes place from 5 days after treatment for GTD. Cu IUD is UKMEC 3/4 though
33
Sterilisation following GTD
Tubal occlusion should ideally be performed after some time has elapsed after surgical evacuation for GTD. Women who request tubal occlusion to be performed at the time of surgical treatment should be advised of the possible increased failure rate and risk of regret. WHOMEC recommends that women with persistently elevated hCG levels or malignant disease should delay being sterilised.
34
Misoprostol
Misoprostol is a synthetic prostaglandin E1 analogue which acts on receptors found in the uterus/cervix and the gastric mucosa. Its main effects include: (1) Uterotonic/cervical ripening: - Collagenase activation causing collagen breakdown within the cervical stroma - Myometrial smooth muscle contraction - Reduction in cervical tone (2) Gastroprotection: - Inhibits gastric parietal cell acid secretion - Increases bicarbonate production
35
Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome)
Congenital absence or underdevelopment of the Müllerian ducts, resulting in agenesis or hypoplasia of the uterus and upper two-thirds of the vagina. Normal ovaries and external genitalia are present. The ovaries remain functional leading to normal development of secondary sexual characteristics. Epidemiology: Affects approximately 1 in 4,500 female births. Second most common cause of primary amenorrhea after gonadal dysgenesis. Pathophysiology: Arrest of embryological development of the Müllerian ducts between the 4th and 12th week of gestation. Exact etiology is unknown but likely multifactorial. May have associated renal, skeletal, and cardiac anomalies due to shared embryological origins. Clinical Features: Reproductive: Primary amenorrhea with normal secondary sexual characteristics (due to functional ovaries and normal hormonal profile). Infertility (absent uterus). Anatomical: Short or absent vaginal canal. Normal external genitalia. Associated Anomalies: Renal (e.g., unilateral agenesis, ectopic kidney). Skeletal (e.g., scoliosis, vertebral anomalies). Less commonly, hearing and cardiac defects. Diagnosis: Clinical Evaluation: History of amenorrhea. Physical examination revealing a shortened vaginal canal. Hormonal and Chromosomal Testing: Normal karyotype (46,XX). Normal levels of FSH, LH, and estrogen (distinguishing from gonadal dysgenesis). Imaging: Pelvic ultrasound or MRI to confirm absent uterus and evaluate for renal anomalies. Differential Diagnosis: Androgen insensitivity syndrome (46,XY with testicular feminization). Transverse vaginal septum or imperforate hymen. Management: Psychological Support: Early counseling to address emotional and psychological concerns. Surgical/Vaginal Reconstruction: Non-surgical: Vaginal dilators to create a functional vaginal canal (first-line). Surgical: Neovagina creation if non-surgical methods fail. Fertility Options: Assisted reproductive techniques (e.g., surrogacy, adoption). Monitoring and Multidisciplinary Care: Address associated anomalies with urological and orthopedic input. Prognosis: Normal life expectancy and sexual function achievable with appropriate treatment. Infertility is a major concern but can be managed with modern reproductive options.
36
MURCS Syndrome (Müllerian-Renal-Cervicothoracic-Somite Abnormality)
Rare congenital disorder that is a variant of Müllerian agenesis, characterized by: Müllerian agenesis. Urinary (renal) anomalies. Renal and Cervicothoracic somite abnormalities (skeletal anomalies). It is considered a broader syndrome involving both MRKH syndrome features and additional systemic anomalies. Clinical Features: (1)Müllerian Agenesis: Primary amenorrhea. Absent uterus and upper two-thirds of the vagina. Normal secondary sexual characteristics. (2)Renal Anomalies: Renal agenesis (unilateral or bilateral). Ectopic kidney or horseshoe kidney. Ureteric abnormalities. (3)Skeletal Anomalies: Cervical or thoracic vertebral defects (e.g., fused vertebrae, scoliosis, Klippel-Feil syndrome). (4) Additional Features: May include hearing loss or cardiac defects. Diagnosis: Clinical Presentation: History of primary amenorrhea with normal pubertal development. Imaging:Pelvic ultrasound or MRI to identify Müllerian anomalies. Renal ultrasound for associated kidney anomalies. X-rays or CT scans for skeletal abnormalities. Genetic Testing: Not routine but may help identify syndromic links in familial cases. Differential Diagnosis: MRKH Syndrome (distinguished by absence of significant skeletal or renal abnormalities). VACTERL association (Vertebral, Anorectal, Cardiac, Tracheoesophageal, Renal, and Limb anomalies). Management: Müllerian Agenesis: Vaginal dilators or surgical neovagina for sexual function. Renal Anomalies: Nephrology follow-up to monitor renal function and treat any complications. Skeletal Anomalies: Orthopedic and neurological evaluation for spinal deformities.
37
Methotrexate
Competitive inhibitor of dihydrofolate reductase (DHFR). DHFR is a key component of the tetrahydrofolate pathway, which is required for synthesis of amino and nucleic acids. 50mg IM in ectopic
38
Mifepristone
Competitive progesterone receptor antagonist Mechanism of action: Inhibits progestogenic effects on the endometrium and myometrium Degeneration of the decidual endometrium (which can cause detachment of the trophoblast and reduced synthesis of bHCG by the syncytiotrophoblast) Cervical softening and dilatation Increases contractility of myometrium and its sensitivity to prostaglandins
39
Complications and risks of abortion medical
CHOICES Continuing pregnancy (1–2 in 100) Hit again (further intervention to complete procedure) <14 weeks: 70 in 1000 /// >14 weeks: 13 in 100 Opening (rupture) of uterus Less than 1 in 1000 for secondtrimester medical abortions - uterine scar (prev CS is a risk factor) Infection Less than 1 in 100 (prophylactic abx used in STOP) Continued blood loss req transfusion <20 weeks: less than 1 in 1000 /// >20 weeks: 4 in 1000 E (surg only) S (surg only) The medications can cause nausea, vomiting, diarrhoea, chills and fever (1 in 10). Abdominal cramping can last, on and off, for a week and bleeding for two to three weeks.
40
Complications and risks of abortion surgical
CHOICES Continuing pregnancy 1 in 1000 (higher in <7/40) Hit again (further intervention to complete procedure) <14 weeks: 35 in 1000 /// >14 weeks: 3 in 100 Opening (rupture) of uterus (no surgical stats) Infection Less than 1 in 100 (prophylactic abx used in STOP) Continued blood loss req transfusion <20 weeks: less than 1 in 1000 /// >20 weeks: 4 in 1000 Entry (uterine perf) 1–4 in 1000 Shock (cervical, and other cervical injury from dilation and manipulation) 1 in 100 The medications can cause nausea, vomiting, diarrhoea, chills and fever (1 in 10). Abdominal cramping can last, on and off, for a week and bleeding for two to three weeks.
41
Cervical prep for STOP
Before 12 weeks of pregnancy: * mifepristone 200mg orally, 24–48 hours before the procedure, * misoprostol 400 micrograms sublingually, 1–2 hours before the procedure, * misoprostol 400 micrograms vaginally or buccally, 2–3 hours before the procedure. 12–18+6 weeks of pregnancy: * combination of mifepristone and misoprostol (using above regimens, sometimes need more than one dose of miso), or * osmotic dilators plus either mifepristone or misoprostol, or with both mifepristone and misoprostol (using above regimens in all cases). 19–24 weeks of pregnancy: * osmotic dilators plus either mifepristone or misoprostol, or with both mifepristone and misoprostol (using above regimens in all cases). Osmotic dilators are advised for cervical preparation from 14 weeks gestation. Misoprostol can also be considered as an alternative (up to 18 weeks gestation), however its efficacy is inferior to osmotic dilators.
42
Anti-D and abortion
If available, anti-D should be offered to non-sensitised RhD-negative individuals from 12 weeks of pregnancy and provided within 72 hours of the abortion.
43
Abx in STOP
The optimal regimen is not known but nitroimidazoles (e.g. metronidazole), tetracyclines (e.g. doxycycline) and penicillins have been shown to be effective. The following regimen can be considered for surgical (or incomplete) abortion antibiotic prophylaxis: * oral doxycycline 100mg twice a day for 3 to 7 days, starting within 2 hours of the procedure (there is evidence that a 3-day course is as effective as a 7-day course).
44
Meiotic non-disjunction
Failure of chromosome separation during cell division (anaphase) Most common mechanism of trisomy Strongly associated with increasing maternal age
45
Robertsonian translocation
Results from breakage of two acrocentric chromosomes (numbers 13, 14, 15, 21, 22) at or close to their centromeres, with subsequent fusion of their long arms to form one chromosome. Loss of Genetic Material: The short arms of the chromosomes contain repetitive sequences (such as ribosomal RNA genes), so their loss usually does not result in major health issues. However, the loss can impact fertility or cause chromosomal imbalances in offspring. Most common 13/14 Next most common 14/21 Carrier is healthy (they have 45 chromosomes instead of the usual 46, but can pass on unbalanced translocations to their offspring) Balanced Robertsonian Translocation:No loss of genetic material, meaning the person with the translocation typically shows no symptoms. Unbalanced Robertsonian Translocation: If an individual inherits an unbalanced combination (e.g., an extra chromosome), it can lead to genetic disorders like Down syndrome (trisomy 21), if an extra copy of chromosome 21 is involved. Trisomy 13 - patau syndrome (not compatible with life) (In up to 1 in 10 pateau caused by translocation) Trisomy 21 - down syndrome
46
Primary oocytes remain suspended in which stage of meiosis until ovulation?
Prophase I During oogenesis immature oogonium mature into the primary oocyte Primary oocytes start meiosis however are quickly suspended in prophase I until ovulation The LH surge at ovulation causes meiosis I to resume however it becomes suspended again at metaphase II At fertilisation, meiosis recommences and completes Summary of Pauses and Suspensions in Oogenesis: (1) Prophase I (Primary Oocyte): Arrested from fetal development until puberty. (2) Metaphase II (Secondary Oocyte): Arrested just before ovulation, resuming at fertilization. (3) Completion of Meiosis II: Happens only after fertilization when the secondary oocyte is activated by the sperm.
47
Meiosis vs Mitosis
Mitosis and meiosis are both types of cell division, but they differ in several ways: (1) Purpose Mitosis is a process that occurs during growth and tissue repair, while meiosis is a process that occurs during sexual reproduction. (2) Products Mitosis produces two identical daughter cells, while meiosis produces four non-identical, haploid sex cells or gametes (sperm and ova in humans) (3) Number of chromosomes Mitosis produces diploid cells, while meiosis produces haploid cells, which have half the number of chromosomes as the parent cell. (4) Tetrad formation Tetrad formation occurs during meiosis, but not during mitosis. In prophase I of meiosis, homologous chromosomes pair up to form a tetrad, which consists of four chromatids. Steps Before either mitosis or meiosis occurs, cells go through a preparatory process called interphase, where they grow and make a copy of their genetic information. The steps of mitosis are prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis. The steps of meiosis are prophase I, prometaphase I, metaphase I, anaphase I, telophase I, and cytokinesis I; and then again II
48
Steps of mitosis
Mitosis has six phases apart from interphase. The first five phases divide the nucleus and its genetic information in half, while the final step splits the entire parent cell into two identical daughter cells. The phases of mitosis are: Prophase: Chromosomes, which contain genetic information, condense and prepare to attach to the spindle—a cellular machine that moves chromosomes during cell division. Prometaphase: The nuclear membrane—a structure that typically contains the chromosomes—breaks apart, the spindle forms, and chromosomes attach to its strong, hollow fibers. Metaphase: Chromosomes align along the spindle’s center. Anaphase: Chromosomes pull apart and move toward the spindle’s poles, which also move apart. Telophase: New nuclear envelopes form around the two separated sets of chromosomes. Cytokinesis: Cells divide.
49
Steps of meiosis
Meiosis has similar steps to mitosis but with two sets of divisions. The first division results in two cells that each have two sets of chromosomes, like in mitosis. The second division creates four cells that each contain one set of chromosomes, because the genetic information isn’t copied a second time. One unique feature of meiosis, which takes place during the first round of prophase (prophase I), is a process called crossing over. DNA is mixed between matching chromosomes from the different parents, increasing the genetic diversity.
50
Aneuploidy
Aneuploidy is where there is loss or gain of a whole chromosome. This is often due to nondisjunction where there is failed separation of chromosomes during anaphase, so either whole chromosomes (error occurring in meiosis I) or chromatids (error occurring in meiosis II) move to the same pole of the cell. This leaves one gamete short of some genetic information, and the other with additional genetic information. Monosomy – one copy of a chromosome, e.g. Turner syndrome (45, X) Trisomy – three copies of a chromosome, e.g. Edward’s syndrome (trisomy 18)
51
Translocation
Abnormalities in chromosome structure are often due to translocations, where there is an exchange of material between two chromosomes, resulting in an abnormal rearrangement. If there is no gain or loss of genetic material, this is a balanced translocation, however, if the exchange of chromosomal material results in extra or missing genes in a daughter cell, it is known as unbalanced and can have clinical effects. There are two types of chromosomal translocation. Reciprocal translocations take place when the chromosomes break within the arms of the chromosome and Robertsonian translocations take place when whole chromosomes join end to end.
52
Types of chromosomal abnormalities
Aneuploidy: abnormal number of chromosomes in a cell (e.g. Trisomy Downs 21, Monosomy Turner X) Translocation: rearrangement of chromosomes where part of one chromosome breaks off and attaches to another chromosome. Can be balanced (where there is no loss or gain of genetic material) or unbalanced (where genetic material is lost or gained). (e.g. Philadelphia chromosome, which is a translocation between chromosomes 9 and 22, linked to chronic myelogenous leukemia.) Inversion: This occurs when a segment of a chromosome is reversed or inverted. The genetic material is rearranged, but the amount of genetic material does not change. It can lead to issues if the inversion disrupts important genes or the chromosome's ability to pair properly during cell division. Duplication: A portion of the chromosome is duplicated, resulting in extra copies of a segment of DNA. This can lead to disorders if the duplicated genes are expressed abnormally. (e.g. Charcot-Marie-Tooth disease type 1A, duplication on chromosome 17) Deletion: A segment of the chromosome is missing, resulting in the loss of genetic material. Depending on the size and location of the deletion, this can lead to various genetic disorders, such as cri-du-chat syndrome. Isochromosome: A chromosome that has identical arms due to the loss of one arm and duplication of the other. This can lead to conditions like Patau syndrome (trisomy 13). Ring Chromosome: A chromosome that forms a ring shape due to the ends of the chromosome being fused together. This can lead to genetic disorders because of the loss of genetic material at the ends of the chromosome.
53
Pregnancy test MOA
Urine pregnancy testing is a type of sandwich enzyme-linked immunosorbent assay (ELISA) and utilises monoclonal antibodies to detect HCG present within urine. Mechanism: When urine comes into contact with the test strip, it passes through the capillary bed. Along the strip, there are three important zones: Reaction zone Test zone Control zone As urine passes into the ‘reaction’ zone, monoclonal antibodies specific to HCG bind to any HCG present within the urine and these HCG-antibody complexes are carried along the strip. Any unbound antibodies will also be carried along the strip. At the ‘test’ zone, there are more anti-HCG antibodies which are fixed to this area of the strip. They will bind to the HCG component of the HCG-antibody complexes and a chemical reaction between them results in a colour change. This causes the test zone of the strip to change colour. If there is no HCG within the sample, the antibodies will not bind and no colour reaction will take place. The antibody complexes will continue to travel along the strip to the ‘control’ zone. Antibodies located in the control zone will bind to the antibody component of the HCG-antibody complex. If there is no HCG present, the antibodies at the control zone will still bind to the antibodies that have traveled up from the reaction zone and a colour change will occur. This confirms that the test has worked.
54
In women aged 40-44 years, what proportion of pregnancies result in miscarriage?
51%
55
Diagnostic ultrasound scanning in early pregnancy is commonly performed at what frequency?
Pelvic ultrasound typically uses frequencies of 3.5 – 7.0 megahertz (MHz), with the - transabdominal transducer using 3.5 – 5.0 MHz - transvaginal transducer >5 MHz For comparison, the upper limit of human hearing is approximately 20 kilohertz (KHz)
56
MTOP UPT following
(1) low-sensitivity urine pregnancy test (detection limit 1000IU hCG) from 2 weeks after treatment or (2) high-sensitivity test (detection 50IU hCG or less) from 4 weeks after treatment.
57
What % of twins in the UK are monochorionic?
30%
58
Fetal Haemaglobin
The primary form of haemaglobin from around 12 weeks gestation to 6 months post-partum (50% when born) Synthesis begins at around 6 weeks gestation Composed of the heme subunits: alpha, alpha, gamma, gamma The gamma subunit has a high binding affinity for oxygen and is encoded by chromosome 11
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The vitelline duct connects the embryo to the yolk sac during early embryonic development. Failure of vitelline duct closure leads to what congenital abnormality?
The yolk sac derives from the hypoblast and is connected to the midgut of the embryo via the vitelline duct (also known as the omphaloenteric duct or omphalomesenteric duct). Development begins during week 2 of embryonic development and becomes visible on ultrasound from 5 weeks gestation. The yolk sac spontaneously separates from the embryo via obliteration of the vitelline duct. Failure of the vitelline duct to close results in Meckel’s diverticulum, the most common congenital abnormality of the small bowel (often asymptomatic).
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Gestational choriocarcinoma Define Prevalence Ultrasound appearances
Malignant transformation of trophoblastic tissue Rare: 1 in 50,000 pregnancies More common with abnormally developing pregnancies such as complete molar pregnancy (50%) or ectopic pregnancy/miscarriage (25%) 2% of complete molar pregnancies result in choriocarcinoma Metastatic spread is most commonly to the lungs Management: Chemotherapy Ultrasound appearances: Heterogenous mass within an enlarged uterus Invasion of the myometrium Cystic spaces associated with haemorrhage No fetal parts
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Confirming miscarriage on USS
1. Look for Fetal HB. No HB: (a) if visible fetal pole, measure the crown–rump length (CRL) (b) if no visible fetal pole, measure mean gestational sac diameter (MSD) 2. CRL TVS < 7 mm : second scan min 7 days after first 7mm or more : seek second opinion and/or second scan min 7 days after first 3. CRL TA record the size of the CRL and perform a second scan a minimum of 14 days after the first before making a diagnosis. 4. MSD TVS < 25.0 mm : second scan min 7 days after first 25.0 mm or more : seek second opinion and/or second scan min 7 days after first 5. MSD TA record the size of the MSD and perform a second scan a minimum of 14 days after the first before making a diagnosis.
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Using ultrasound scans for diagnosis of tubal ectopic pregnancy
There IS a tubal ectopic: an adnexal mass, moving separate to the ovary (sometimes called the 'sliding sign'), comprising a gestational sac containing a (1) yolk sac or (2) fetal pole (with or without fetal heartbeat) There is a HIGH PROBABILITY: an adnexal mass, moving separately to the ovary, with (1) an empty gestational sac (sometimes described as a 'tubal ring' or 'bagel sign') or (2) a complex, inhomogeneous adnexal mass, moving separate to the ovary. There is a POSSIBILITY: (1) an empty uterus or (2) a collection of fluid within the uterine cavity (pseudo-sac); this collection of fluid must be differentiated from an early intrauterine sac, which is identified by the presence of an eccentrically located hypoechoic structure with a double decidual sign [gestational sac surrounded by 2 concentric echogenic rings] in the endometrium.
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endometrial cast
An endometrial cast, also known as a decidual cast, is a rare condition where the entire uterine lining is shed in one piece, rather than gradually over several days. Pink, fleshy, and solid, with a shiny appearance, size of palm. Causes: Hormone disruption or imbalance, such as from birth control medication, hormonal treatments, or ectopic pregnancy. Can be mistaken for POC on o/e - still important to do hcgs
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Postabortion hemorrhage
excessive bleeding that requires a clinical response such as transfusion or hospital admission, and/or bleeding in excess of 500mL 0-3 per 1,000 cases following medical abortion up to 9 weeks gestation or vacuum aspiration before 13 weeks gestation, 0.9-10 per 1,000 cases following uterine evacuation at or after 13 weeks gestation Causes of bleeding include placenta previa or accreta, uterine atony, retained products of conception, cervical or vaginal laceration, uterine injury, and coagulopathy
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Take thurough hx: obstetric complications – especially hemorrhage, having had two or more cesarean deliveries, a bleeding disorder, gestational age of more than 20 weeks, fetal death, obesity, increased maternal age, and placenta previa or accreta prevent or prepare for increased bleeding —such as assessing a preabortion hemoglobin or hematocrit, ensuring uterotonic medications are readily available, preparing for possible transfusion, or referral to a higher-level facility Administration of prophylactic oxytocin or syntocinon (five or 10 units) has not been shown to decrease postprocedure bleeding following first-trimester vacuum aspiration in a clinically meaningful way When administered prior to dilatation and evacuation (D&E) procedures performed between 18-24 weeks, 30 units of oxytocin
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From which gestation are osmotic dilators advised for cervical preparation during STOP?
Osmotic dilators are advised for cervical preparation from 14 weeks gestation. Misoprostol can also be considered as an alternative (up to 18 weeks gestation), however its efficacy is inferior to osmotic dilators.
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Uterine atony
The most common cause of post-partum haemorrhage. Inadequate contraction of the myometrium results in heavy bleeding. The uterus feels soft and distended on palpation. Risk factors include: increased maternal age, high BMI, previous caeserean section, abnormal placentation, bleeding disorders and gestation >20 weeks Acute management: 1. Bimanual uterine massage 2. Uterotonics 3. Re-aspiration/evacuation 4. Intrauterine tamponade (Foley balloon) 5. Urgent senior surgical review When bleeding continues after assurance of complete uterine evacuation and no visible lacerations, providers must consider other complications, such as perforation, coagulopathy or placenta accreta If coagulopathy (e.g. DIC) is present, blood products may be required. Surgical measures including hysterectomy, uterine compression sutures, uterine artery ligation or uterine artery embolization can be performed for severe bleeding that cannot be controlled by other measures. Providers at health centers without available operating theaters or expertise should have clear protocols for resuscitation and transfer to a higher level of care. Individuals at risk of shock require intravenous line placement, supplemental oxygen, fluid resuscitation and replacement of blood products as indicated.
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Uterotonic medications and dosages:
Methylergonovine (Ergometrine) 0.2mg intramuscularly or intracervically; can be repeated every 2-4 hours. Avoid in people with hypertension. Misoprostol 800mcg buccally or sublingually Oxytocin 10-40 units per 500-1000mL fluid intravenously or 10 units intramuscularly Intrauterine tamponade Sterile gauze or, 30-75mL Foley catheter balloon, condom catheter or obstetric balloon placed in uterus
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Cyclizine Histamine H1-receptor antagonist Promethazine Histamine H1-receptor antagonist Ondansetron Serotonin 5-HT3 receptor antagonist Prochlorperazine Dopamine D2 receptor antagonist Metoclopramide Dopamine D2 receptor antagonist 5-HT3 receptor antagonist 5-HT4 receptor agonist
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Toxoplasmosis key points
Toxoplasma gondii is an intracellular protozoan parasite Primary host and source of infection is domestic cats T. gondii oocysts excreted in cat faeces, mature in environment and then ingested by secondary hosts which include humans Fetal consequences more severe if infection takes place within 10 weeks of conception Maternal-fetal transmission risk increases as the pregnancy proceeds but the consequences become less severe May cause miscarriage or fetal abnormalities such as microcephaly, hydrocephalus, cerebral calcifications, cerebral palsy, epilepsy choroidoretinitis and thrombocytopenia. Diagnosis can be via PCR or Immunoglobulins (IgM,IgG and IgA). MRI/CT may show ring enhancing lesions in CNS tissues. Treatment not usually required in the immunocompetent. In pregnancy treatment is indicated if recent infection suspected Treatment varies depending on local protocols (Spiromycin or combination of pyrimethamine, sulfadiazine, and folinic acid)
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Beta Thalassemia: what is it?
1 in 100,000 global incidence / 70,000 babies born with thalassaemia each year Caused by mutation HBB gene Chromosome 11 Autosomal Recessive Inheritance: Homozygous b-thalassaemia (Major) produces severe transfusion dependent anaemia Heterozygote b-thalassamia (Minor/trait/carrier) produces mild microcytic anaemia
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Beta Thalassemia: management in preg
Diabetes should be screened for and well controlled. If detected refer diabetologist Thyroid function should be screened and patients maintained as euthyroid Patients should be assessed by a cardiologist and have ECG, echo and T2 cardiac MRI All patients should have Biliary ultrasound & have FerriScan or Liver T2 All women should be offered bone density scan Folic acid 5 mg daily should be commenced 3 months prior to conception in these patients All women with thalassaemia major should be receiving blood transfusions on a regular basis aiming for a pretransfusion haemoglobin of 100 g/l
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Beta Thalassemia: Extra Scanning in Pregnancy
Women should be offered an early scan at 7 to 9 weeks of gestation In addition to the routine first trimester scan (11-14 weeks of gestation) and a detailed anomaly scan at 18-20+6 weeks of gestation, women should be offered serial fetal biometry scans every 4 weeks from 24 weeks of gestation
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Beta Thalassemia: Thromboprophylaxis
Women with thalassaemia who have undergone splenectomy and have a platelet count >600 should be offered LMWH & Aspirin (75 mg/day) Women with thalassaemia who have undergone splenectomy or have a platelet count >600 should be commenced on Aspirin (75 mg/day) Women with thalassaemia who are not already using prophylactic low-molecular-weight heparin should be advised to use it during antenatal hospital admissions
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Why are AFP and hCG the most important serum markers in preg
HIGH AFP - think neural tube defect or multiple pregnancy! HIGH hCG (or inhibin A) think Downs! HIGH hCG think Edwards!
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Turners: Karyotype
Turners may be complete monosomy of the sex chromosomes where the karyotype is termed 45 X or show a mosaic pattern with variable penetration of cell types with the single X chromosome. Complete monosomy accounts for 50% of cases. Turners syndrome is common in utero affecting 1-2% of all conceptuses however 99% of these will miscarry and only 1% will survive to term. Turners occurs in 1 in 2000 live births.
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Turners: biochem
Biochemically (after age 10) raised FSH and LH Thyroid dysfunction also common
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Downs screening
11+0 to 13+6. Triple test = AFP, hCG and uE3 Quadruple test = AFP, hCG, inhibin-A and uE3 Combined test = PAPP A and hCG and Ultrasound
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CAH cause
90% of cases are due to 21-hydroxylase deficiency as a result of abnormal CYP21A genes. This results in androgen excess and mineralocorticoid deficiency. 5% of cases are due to 11-hydroxylase deficiency.
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Down Syndrome cause
Nondisjunction accounts for approximately 95% of Down Syndrome. 88% is due to nondisjunction of the maternal gamete 8% is due to the paternal gamete Mitotic Nondisjunction after conception leads to mosaicism. Translocation Down Syndromes account for 4.5% of Down Syndromes
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Causes of first trimester miscarriages
Turner Syndrome is responsible for around 10-15% of all first trimester miscarriages. Trisomies are thought to be responsible for 68% of first trimester miscarriages.
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Noonan
Autosomal dominant condition Characteristic phenotype includes short stature, chest deformity, congenital heart defects, and unusual facial features. Coagulation defects, cryptorchidism in men (absence of at least one testicle, and may manifest delayed puberty), and lymphatic dysplasia are not uncommon.
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Cri-du chat
Syndrome caused by micro deletion of chromosome 5 Common symptoms include a unique cry that sounds like the mewing of a cat, characteristic facial features, slow growth and a head that is smaller than expected (microcephaly).
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Risk of Down Syndrome with Maternal Age
1:1,500 at 20 years 1:900 at 30 years 1:100 at 40 years >1:50 at 45 years and over
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Maternal mortality rate for women >40 years vs women aged 20-24 years
Maternal mortality rate for women >40 years is 3 times greater than for women aged 20-24 years
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Most common cause of miscarriage
aneuploidy - most common of these ds
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Women >40 and ectopics
Women >40 years are also 3 times as likely to experience an ectopic pregnancy
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Fertility for 40-44 and 45+ (rates of conception in one year)
40-44 years is 10-20% 45-49 years ~12%
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Pregnancy when does BP begin to fall and when is it at it's lowest
Blood pressure begins to fall from as early as 8 weeks gestation BP is lowest at ~ 24 weeks gestation Rises again towards end
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ALP and pregnancy
ALP produced by placenta Raise x 3 normal
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Ectopic Incidence and where they occur
UK Incidence of ectopic pregnancies is 1 in 90 (just over 1%) Tubal 95% (80% ampulla, then isthmus then fimbrial) Only ~3-5/100 ectopics occur outside of the fallopian tubes: Interstitial 2% Ovarian 0-3% Abdominal 1% Cervical <1% Heterotopic <0.1%
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When is intrauterine sac seen on TV USS (and ABDO USS)
An intrauterine sac should be seen on TV USS in a normal pregnancy once HCG reaches 1500 – 2000mIU/mL Pregnancy may not be seen until HCG >6000 for abdominal USS
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Methotrexate suitable for ectopic in what situations:
*No significant pain *Unruptured ectopic pregnancy <35mm with no visible heartbeat *Serum HCG <1500 *Confirmed absence of intrauterine pregnancy (teratogenic) *Need to be able to attend for follow up HCG monitoring until returns to non-pregnant levels Take HCG levels on day 4 and 7 following administration If falls by >15% between days 4-7 then it should be taken weekly until <15 If does not fall by 15% then repeat TV USS and consideration of second dose Note: With HCG between 1500 – 4999 and fulfils all other criteria for medical management, the patient has a choice between medical or surgical management options, though NICE recommends MTX firstline
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Methotrexate failure rate
15% of patients may need a second dose of MTX 7% of patients may require surgical management as a result of failed medical management
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Miscarriage: when to review if expectant management
Can be offered if a trial of expectant management unsuccessful, following a repeat confirmatory USS : No bleeding after 7-14 days (miscarriage process not started) Ongoing bleeding after 7-14 days (incomplete miscarriage) (can cont if generally well but check up every 14 days)
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Investigations for recurrent miscarriage
(1) CLOTTING Antiphospholipid syndrome: lupus anticoagulant (most strongly associated) and anti-cardiolipin antibodies + Testing may be recommended for inherited thrombophilias, especially if a history of second trimester loss (with which they are more strongly associated) Factor V leiden > prothrombin gene mutation > Protein S deficiency Routine testing for protein C and antithrombin deficiency is not recommended (2) THYROID TFTs –subclinical hypothyroidism (TSH > 4.0) has been associated with miscarriage Thyroid peroxidase antibodies (TPOAbs); considered most sensitive marker of thyroid autoimmunity and presence of these antibodies is associated with miscarriage (RCOG) (3) IMAGING To look for congenital uterine anomalies (TV USS +/- 3D imaging) Increased risk of miscarriage with septate and bicornuate uterus (4) GENETICS Parental chromosomal abnormalities, especially translocations, are associated with recurrent miscarriage Parental karyotyping should be performed if pregnancy tissue analysis confirms presence of an ‘unbalanced structural chromosomal abnormality’ OR In instances where pregnancy tissue cytogenetics was to be performed but inadequate tissue was salvaged (5) TISSUE ANALYSIS Should be offered on pregnancy tissue from third and subsequent miscarriages or any second trimester loss
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Management of recurrent miscarriage: If APLS is diagnosed:
treat with aspirin 75mg and heparin until at least 34 weeks gestation
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complete vs partial molar preg
1:700 Complete: 1 or 2 sperm fertilise(s) an ‘empty’ ova (containing no genetic material) . 2 sets of chromosomes both paternal Partial 2 sperm fertilise a normal ova   Developing pregnancy has 3 sets of chromosomes 
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Follow up for partial molars: 
Until HCG negative   2 x negative HCGs at least 4 weeks apart 
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Follow up for complete molars: 
Until HCG negative   2 x negative HCGs at least 4 weeks apart  ****Minimum 6 months follow up HCG monitoring ****
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Rate of gestational trophoblastic neoplasia (GTN) in molar pregs and rx
1 in 7 for complete molars  1-2 in 200 for partial molars   Chemotherapy continued until + 6 weeks after HCG returned to normal (negative)  Advised not to conceive following chemotherapy for GTN for a further 12 months following completion of treatment 
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Does one molar preg put you at risk for future molar preg?
After 1st molar risk increases from ~1: 700 at baseline to ~1: 100 (1%) (Lower risk of recurrence for partial compared to complete molars) After 2 consecutive molar pregnancies, the risk of further recurrence is significantly higher(~20%)
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maternal health screen antenatal - whats included?
Rhesus status/disease Sickle cell and thalassaemia Sexually transmitted infections Blood borne viruses
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Combined screening
10-14 weeks (CRL must be between 45 mm – 84 mm) Maternal age (>=35 years is higher risk) Weight Fetal nuchal translucency on USS (Abn >=3mm or >99th percentile for gestational age) Maternal serum HCG and PAPP-A Low risk (risk of being effected < 1 in 150) -> no further testing required/ recommended High risk (risk of being effected between 1: 2 – 1: 150) -> recommendation/ offer of further tests
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Low PAPP-A
PAPP-A is a protein produced by the placenta Low PAPP-A associated with growth restriction, preterm delivery and pre-eclampsia If low PAPP-A identified, aspirin 150mg OD is recommended until 36 weeks gestation
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quadruple screening
14+3 – 20 Blood test only which looks at maternal serum: HCG AFP (alpha-fetoprotein) Inhibin A Unconjugated oestriol (uE3) In the UK, this test is only used to screen for Down’s syndrome and spina bifida risk Down’s syndrome is associated with low AFP and uE3, alongside raised HCG and Inhibin A Isolated raised AFP can suggest higher risk of spina bifida
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quadruple screening mneumonics
DOWNS - HI (hello) HIGH - H(cg) and I(nhibin A) LOW - AFP and uE3 EDWARD is a boys name, HE is feeling LOW LOW - H(cg) and uE3 N/ LOW others Raised AFP alone - spina bifida or multiple pregs
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Downs
trisomy 21 Generally good survival rates and average life expectancy into the 60s Wide variety of severities, both in intellectual disability and associated physical health conditions Only ~5% of babies born with Down’s syndrome die before their 1st birthday
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Edwards
Trisomy 18 Low survival rates; high rates of death in utero / around delivery Of babies born alive, only ~13% live past 1st birthday
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Pataus
trisomy 13 Low survival rates; high rates of death in utero / around delivery Of babies born alive, only ~11% live past 1st birthday
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Sex chromosome aneuploidy Most common Viable monosomy
Klinefelter’s (47 XXY, not screened for) is the most common sex chromosome aneuploidy, Turner’s syndrome (45XO, not screened for) is the only viable chromosomal monosomy
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Non-invasive pre-natal testing (NIPT); a further screening test
Offered via NHS if high risk result (1 in 2 – 1 in 150 risk) from combined or quadruple screening Can be performed from 10 weeks of pregnancy -> no upper limit Maternal blood sample only so no risk of harm to pregnancy More accurate than combined or quadruple screening but still considered a screening test Results again are given as low or high risk: If low risk, no further NHS testing is offered If high risk, an invasive diagnostic test would be offered
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false + on NIPT
Occurs if placental mosaicism (rare) the placental cell free DNA picked up in maternal circulation is not reflective of the fetal genome
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Contra indications / not suitable for NIPT
Active cancer (tumours can release cfDNA) On immunotherapy Recipient of blood transfusion within last 4 months Previous stem cell therapy, bone marrow or organ transplant Vanished twin pregnancies Triplet or higher multiple pregnancies Maternal Down’s syndrome or chromosomal translocations
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Chorionic villous sampling;
Invasive, diagnostic 11+0 – 13+6 Sample of tissue taken directly from placental bed (chorionic villi), under USS guidance Note on when can be preformed: (a) Can be performed from 10 weeks, should NOT be performed prior to 10 weeks due to possible association with oromandibular and limb defects (b) If required, can also be performed from 14+0 – 14+6 (should not be performed beyond this) More time to consider results/ reach decisions >amniocentesis TA vs TC: Transcervical associated with higher bleeding risk (10 in 100) but no greater miscarriage risk Important risks: (1) ~1 in 200 (0.5%) risk of miscarriage (RCOG – states no difference in risk amnio vs CVS with trained operator, but that risk is likely to be operator dependent) (2) ~ 1 in 1000 risk of infection (slightly higher than amniocentesis) (3) Risk of rhesus sensitisation; anti-D is given to Rh- mothers undergoing amniocentesis or CVS (3) Small chance of inadequate sample and repeat procedure needed
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Amniocentesis;
invasive, diagnostic 15-20/40 Sample of amniotic fluid is aspirated trans-abdominally, under USS guidance Increased risk of club foot only if performed <15/40– therefore this is not recommended Less time to consider results/ reach decisions < CVS Important risks: (1) ~ 1 in 200 (0.5%) risk of miscarriage (RCOG – states no difference in risk amnio vs CVS with trained operator, but that risk is likely to be operator dependent) (2) <1 in 1000 risk of infection (slightly less than CVS) (3) Risk of rhesus sensitisation; anti-D is given to Rh- mothers undergoing amniocentesis or CVS (4) Small chance of inadequate sample and repeat procedure needed
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Abortion Act 1967
legal limit 24/40 if terms met (1) Performed by registered medical practitioner (2) In NHS hospital/ approved location (now includes woman’s home up to 10 weeks - can be done up to 12 weeks) (3) 2 medical practitioners must agree it is justified under a clause of the HSA1 Termination procedures must be notified within 7 days to the CMO
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HSA1 form
HSA1 form – grounds for carrying out an abortion Majority of abortions (98%) carried out in the UK are undertaken via clause C of HSA1 1.6% were carried out under ground E A very small minority are carried out using other clauses of the HSA1 Clauses (A) cont preg risk to the life of the preg woman greater than if preg was terminated (B) term necc to prevent PERMANENT INJURY to physical/ mental health of preg woman (C) preg not exceeded 24wk and cont would involve risk, greater than if preg were terminated, injury to mental/physical health of woman (D) preg not exceeded 24wk and cont would involve risk, greater than if preg were terminated, injury to mental/physical health of existing kids or woman's fam (E) substantial risk that if child born, would suffer from physical/ mental anomalities -> severly handicapped.
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Medical abortion regime
mifepristone 200mg PO -> misoprostol 800mcg 24-48 hours later (effectiveness of single dose 800mcg misoprostol starts to decline from 9 weeks gestation) At <12 weeks gestation, RCOG advises that further doses misoprostol (400mcg/ further dose) may be required at 4 hourly intervals until pregnancy expelled (At <12 weeks gestation, if mifepristone not suitable or not available – 800mcg misoprostol -> 400mcg + 3 hourly intervals) Beyond 12 weeks, MTOP should take place in a medical facility due to increased risk of adverse effects/ multiple misoprostol doses required (3 hourly) **When being used >24 weeks lower doses of misoprostol should be used, with increased intervals between doses (especially for this with uterine scars) to reduce rupture risk **
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Surgical abortion
<14 weeks STOP should be performed via MVA/EVA No lower limit for use, but higher rates of ongoing pregnancy at <7 weeks gestation MVA/EVA can be performed up to 16 weeks if operator confident and appropriate equipment available (16mm cannulae) but this is not routine recommendation D&E is recommended from >14-24 weeks gestation The safest and most effective method of STOP at >14 weeks gestation Note – dilation and curettage (D&C) is an obsolete method of STOP and should not be used
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Abortion risks med vs surg Cont preg Further Ix Infec Bleeding req PRC Cervical injury Perf Rupture
MEDICAL Cont preg 1-2 in 100 Further Ix <14wk 7in100, >14wk 14in100 Infec <1 in 100 Bleeding req PRC <20wk <1in1000; >20 4in1000 Cervical injury NA Perf NA Rupture <1 in 1000 for 2/3rd trimester SURG Cont preg 1in1000(higher if <7wk) Further Ix <14wk 3.5in100, >14wk 3in100 Infec <1 in 100 Bleeding req PRC <20wk <1in1000; >20 4in1000 Cervical injury 1 in 100 Perf 4 in 1000 Rupture NA
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Cervical preparation prior to STOP at <12 weeks
single agent Oral mifepristone 200mg 24-48 hours prior Misoprostol 400mcg buccally or vaginally 3-4 hours prior Misoprostol 400mcg sublingually 1-2 hours prior
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Cervical preparation prior to STOP 12-18+6 weeks
2 agents +/- osmotic dilators: Combination of mifepristone AND misoprostol +/- osmotic dilators
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Cervical preparation prior to STOP from 19+ weeks
osmotic dilators and at least one agent: Osmotic dilators recommended PLUS mifepristone and/or misoprostol
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Contraindications to medical abortion:
Known or suspected ectopic pregnancy Previous allergy to mifepristone or misoprostol Severe uncontrolled asthma* (requiring oral steroids) Chronic adrenal failure* Porphyria* *Contraindicates use of mifepristone but misoprostol alone could be considered
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Prophylactic antibiotics and abortion
Not required for medical abortion procedures; ARE recommended following surgical abortions Oral doxycycline 100mg BD for 3-7 days typically Abx prophylaxis should be commenced within 2 hours of procedure Evidence shows a 3 day course is just as effective as a 7 day course Optimal regime not evidence based – other suitable agents include metronidazole/penicillins
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MTOP UPT following
Low sensitivity urine pregnancy test (detection HCG >=1000-1500) at +2 weeks High sensitivity urine pregnancy test (detection HCG >=25-50) at +4 weeks
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RPOC on USS
endometrial thickness >=15mm widely accepted as diagnostic (If infection present, removal of tissue = more urgent and surgical management is recommended)
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Mifepristone MOA
Competitive progesterone receptor antagonist (1) Endometrial decidual degeneration (via apoptosis) (2) Myometrial sensitisation to prostaglandins (3) Cervical softening and dilatation: From 24 hours Maximal effect 36-48 hours Side effects – GI upset, vaginal bleeding, hypotension Unintended effects – anti-glucocorticoid (reduces effect of steroids) Contraindicated in poorly controlled (steroid dependent) asthma or h/o adrenal insufficiency Also porphyria (-> porphyria storm) Is metabolised by P450 system so higher failure rates in concurrent use of inducers
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Misoprostol
Synthetic prostaglandin E1 analogue Type E prostaglandins (A) contractions of smooth muscle of myometrium (B) relaxation of the cervix Sensitivity to prostaglandins increases with gestation (Propess/ Prostin (dinoprostone prostaglandin E2) used for inductions) Vaginal administration -> greater contractility >> oral Vaginal administration increases uterine tone within 20 minutes (peak at 46 mins) Side effects – nausea, D+V, headache, fevers/shivers/ chills Unintended effects: (A) Enhances pain sensation by blocking K+ channels -> increased sensitivity of nerves (B) PV bleeding can be excessive; caution with other bleeding risks i.e. placenta praevia or high risk of uterine scar rupture If given in context TOP and pregnancy continues is associated with birth defects: Moebius syndrome, CNS abnormalities, amniotic band syndrome
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Incubation Period (days) for common an diseases Chickenpox Rubella Influenza Parvovirus (Fifth Disease) Streptococcus pyogenes (Scalet Fever)
Disease Incubation Period (days) Chickenpox 14 (10-21) Rubella 14 (12-23) Influenza 1-3 Parvovirus (Fifth Disease) 4-20 Streptococcus pyogenes (Scalet Fever) 1-7
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hpv in preg treatment
Podophylline is considered potentially teratogenic and shouldn't be used. 5-fluorouracil although not listed would also be inappropriate for the same reason. Imiquimod is not licensed for use in pregnancy Liq nitrogen ok Non treatment is also a safe option.
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what virus fams HIV Rubella Herpes Simplex and CMV Parvovirus B19 (slapped cheek) Hepatitis C
HIV is a retrovirus i.e. a member of the retroviridae family. Its genus is lentivirus Rubella is a Togavirus Herpes Simplex and CMV are members of Herpesviridae family Parvovirus B19 (slapped cheek) is a member of the Parvoviridae family Hepatitis C is a member of the Flaviviridae family
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