Outline of Management of Normal Low Risk Pregnancy See Manitoba Prenatal Record. Important history, physical and lab tests, ultrasound, etc. Pearls: Calculate EDC from LNMP – if accurate most reliable, average 40% unreliable. HCG first detectable in serum 6-8 days after ovulation; >25 IU is considered positive. Initial urine pregnancy test positive (2 mins) 32 days after conception – 1500 MIU/ml. Concentration of about 100 IU/ml is reached about the date of next menses. Most urine pregnancy tests are positive at HCG>25 IU. HCG level doubles every 2.2 days in the first 30 days of normal gestation. Initial perception of fetal movements – 19-20 weeks in Primip, 17-18 weeks in Multip. Fundal height in cm for gestational age – very good correlation between 18-30 weeks. Use of Ultrasound (transvaginal) Gestational sac – at 5 weeks with a mean bHCG 1500 IU/L. Crown rump length (CRL) (6-12 weeks) in centimeters + 6.5 approximate estimate of gestational age. Most accurate measurement – beyond 13th week obtained by averaging BPD, femur length, head circumference and abdominal circumference. Lab Tests First Prenatal Visit: blood type (Rh and antibody screen), CBC, Rubella, Hepatitis B&C, Toxoplasmosis, varicella (if history is negative), VDRL, HIV, Tuberculin test (USA and in some communities in Canada), Cystic Fibrosis. Cervix – Pap, GC, Chlamydia, other Vagina and Rectum – Group B Strep. Bacterial Vaginosis. If Mother is Rh negative then Father’s Rh needs to be done. MSU – culture. Maternal Ultrasound and Serum Marker Screening - Second Trimester. First Trimester: Maternal age >34, previous and family history of congenital anomaly or chromosomal anomaly. Ultrasound – Fetal nuchal transluscency (high in both chromosomal and congenital anomaly). At 16 weeks/Second Trimester – Maternal free beta HCG Pregnancy associated plasma protein (PAPP-A) Both increased in Down’s Syndrome. Check for Trisomy 21, 18; Neural tube defect; ventral wall defect – ultrasound exam. Alphafetoprotein (AFP) Low with Down’s Syndrome. HCG – High in Down’s syndrome. Amniocentesis/CVS (chorionic villi sampling) Uncongugated estriol (amniotic fluid) at 16-20 weeks. High neural tube defect in >80%, also with ventral wall defect. Combination of low MSAFP and elevated HCG, low UE3 has a detection rateof Down’s Syndrome (Trisomy 21) of about 70% with a positive screen result in about 5% of all pregnancies. Incidence Down’s syndrome – 1:700 pregnancies Spina Bifida/Anencephaly – 1:1200 Trisomy 18 – 1:1400 Ventral wall defect/Gastroschesis – 1:3000 Third Trimester CBC, again Rh (if negative and unsensitized) 1 hour PC blood sugar (before 28 weeks), if high GTT HGB A,C (maternal diabetes, prior macrosomic infant, 9 pounds) Rubella titres – if prior titre was 1:8 to 1:16, if suspected exposure to Rubella Cervix – GC, Group B Streptococcus, Herpes Vagina – Bacterial Vaginosis *Genetic Screening – Includes Mother, Father or others in either family. Consider referral to genetics: 1. Maternal age >35 years on EDD 2. History of consanguinity 3. Mediterranean or Asian – Thalassemia 4. Jewish – Tay Sachs 5. African – Sickle Cell Disease or trait 6. Neural tube defect 7. Down’s Syndrome 8. Hemophilia 9. Muscular Dystrophy 10. Maternal PKU 11. Cystic Fibrosis 12. Huntington Chorea 13. Mental retardation 14. Other inherited genetic or chromosomal disorder 15. Mother or baby’s father had a child with birth defect not listed (>2 first trimester abortion or stillbirth. Effects of Smoking, Alcohol, Medications and Physical Activity The most vulnerable time is day 17 to day 56 post conception. Smoking – should be discouraged at all times. Increased risk of abortion, fetal and neonatal death, prematurity, SIDS. Babies born to smoking mothers on average are 200 grams less than non-smoking mothers. Nicotine is concentrated in breast tissue and will be stored and released in milk. Adverse effects of marijuana are not well understood including any street drugs (LSD, “uppers”, “downers”, cocaine, “angel dust”), all are deleterious. Alcohol – There is no absolute safe level. Fetal Alcohol Syndrome (FAS) with prolonged and excessive consumption. Antianxiety Agents - >4 fold increase in severe congenital anomalies. Fluoxetine is now the drug of choice for anxiety and depression in pregnancy and lactation. Antineoplastic Agents – Teratogens. Exposure before 40 days is lethal to embryo. Anticoagulants – Coumarion Derivative (Coumadin) during first trimester (especially between 6 to 9 weeks): Increased Spontaneous Abortion Intrauterine Growth Restriction CNS defect including mental retardation Craniofacial defect (fetal warfarin syndrome) Easily crosses the placenta – bleeding problem in fetus and excreted in milk. Heparin – does not cross the placenta (reported risk prematurity and fetal demise) Anticonvulsants – about 1:200 pregnant women is epileptic. Benefits of seizure prevention against teratogenicity of the drug. Dilantin – Fetal Hydantoin Syndrome – in 10% of exposed fetuses, cranioifacial abnormalities, IUGR, mental retardation and cardiovascular anomalies. Valproic acid – 1-2% risk of open neural tube defect. Phenobartione – neonatal withdrawal syndrome. Hormones Estrogen and Progestin combination (oral contraceptive pills) – OK!! Strong androgenic progestins – masculinization of external genitalia of female fetus increases up to 2%. D.E.S. – teratogen and carcinogen. DES exposure has increased risk of cervical abnormality (cock’s comb cervix), uterine malformations as well as clear cell adenocarcinoma in females. Others: Acutane – CNS, CV and craniofacial defect (ear), microcephaly, abortions and congenital anomalies, increases to >50%. Radiation – dose dependent: teratogenesis, mutagenesis, carcinogenesis. Physical Activity – continue to exercise except in cases of: P.I.H. Preterm labour or ruptured membranes IUGR Incompetent cervix Persistent 2nd or 3rd trimester bleeding. Sexual Activity – OK with the exception that there is a risk of preterm labour, repeated pregnancy loss, persistent 2nd and 3rd trimester bleeding. Methods of Contraception, Risks, Failures Vasectomy – there are no long term hormonal, metabolic or autoimmune effects. Oral contraceptives (O.C.): Failure rate is 0.1 to 2% mainly due to interrupted use. Increased risk of V.T.E. – In non user 1.1/10,000, with O.C. 1-3/10,000 In obese patient – slight decrease in contraceptive efficacy but combined OC is still a good option. Failure rate in obese patients is 13% with OC which is higher than implants, TL, CUIUD and LNGIUS. Intrauterine Devices 1. CUT – Failure rate 0.2%, Ectopic rate 5%. May be used as a postcoital emergency contraception. Can cause increased duration and amount of menses. 2. LNGIUS – releases 20 ug of LNG/day, Failure rate 0.1%, unpredictable bleeding for 3 months, dramatically reduced bleeding in 3-6 months, in 1/3 amenorrhea after 12 months. Implants – Progestin only, lasts for 3 years, failure rate 0.05%, irregular bleeding. Vaginal Ring or Transdermal Patches (Evra) – 3 weeks on, 1 week off, continuously. Failure rate as in O.C., B.T.B., breast tenderness, nausea and bloating. Depo Medroxy Progesterone Acetate 150 mg intramuscular every 12 weeks. Inhibits ovulation Failure rate – 0.2% with perfect use, imperfect use may be 6% Weight gain Breakthrough bleeding. Condom – 10% failure. Female condom. Diaphragm – 13% failure. Foam, Cream, Jelly – 15% failure. Rhythm method – 19% failure. Tuba ligation – failure rate of 0.1 to 0.4% Tubal Micro Insert (Essure) by hysteroscopic method, risk of tubal perforation which may also be late. Emergency contraception – Plan B – one single 1.5 mg Levonorgestoral pill within 72 hours of sex then 12 hours later another pill OR 2 x 75 mg Levonorgestoral pill up to 120 hours OR 1 x 30 mg Ulipristal acetate pill up to 120 hours. Tubal Ligation – Hulka clip, Filsche clip, electrocoagulation and division. Complications – Hemorrhage, tear of mesosalpinx, accidental electrical burns of intestines, abdominal wall, CO2 embolism, anaesthetic complication. Can also be done through vaginal colpotomy. Postpartum – by Pomeroy’s method. Higher failure rate in younger women, <38 years, 5.4%. 6-10% of women seek reversal, many more have remorse. Contraindication to prescribing a pill containing Estrogen A. Arterial or venous thrombosis or the presence of factors which could predispose to this type of complication: History of DVT/PE Ischemic heart disease or CVA Hypertension >160/100 mmHg Diabetes with retinopathy, nephropathy, or neuropathy or diabetic for >20 years. Complicated cardiac vascular disease (pulmonary hypertension, atrial fibrillation, subaortic infections, endocarditis) Presence of known thrombopenic mutations (factor V Liden, Protein S, C or antithrombin deficiency) Migraine with aura or neurological problems (loss of vision, blurred vision, speech or motor disorder) Smoker over age 35 (absolute >15 cigarettes/day) Less than 3 weeks after delivery. B. An estrogen dependent cancer: Breast Cancer Endometrial Cancer (any undiagnosed abnormal uterine bleeding) C. Liver disease Active viral hepatitis Severe decompensated cirrhosis Benign or malignant liver tumor History of cholestasis and/or jaundice related to oral contraceptives. Question: What dose of Ethinyl Estradiol should you prescribe: 20 ug (micrograms) 25 ug 30ug 35 ug Use the lowest done containing 20 ug EE. Are oral contraceptives with 20 ug of Ethinyl Estradiol as effective as pills with 30 ug or 35 ug of EE? Yes. Progestin is responsible for most of the pill’s contraceptive action. Inhibition of LH peak. Thickening of cervical mucous. Altered tubal motility. Inhibition of endometrial thickening. The main role of EE is to stabilize the endometrium. Pearl Index of 0.29. If the patient is obese should I use an oral contraceptive with a higher dose of EE to prevent any risk of pregnancy? No. Higher doses of oral contraceptives should not be prescribed. Obese patients are at greater risk for thrombosis. There is increased risk of thrombosis with higher doses of estrogens. Is an OC containing 20 ug of EE sufficient for patients with Acne? Yes. All low dose OCs have a beneficial effect on acne. Estrogen components of the pill raises SHBG thereby decreasing free testosterone; progestin inhibits release of LH thereby the synthesis of testosterone by the ovaries. Drug Interactions of Oral Contraceptives – Reference CPS. Drugs which may decrease the efficacy of oral contraceptives: Anticonvulsants – Rapid metabolism of Estrogen – use higher dose OCs (50 ug of EE) Increased binding of Progestin and EE to SHBG Fluid retention may increase risk of seizures. Antibiotics and Rifampicin – Enterohepatic circulation disturbance Acceleratin of EE and Progestin metabolism For short course use additional method. For long course use another method. Antifungals – Griseofulvin – Stimulate hepatic metabolism Use other method. Cholesterol Lowering Agent – Reduces elevated serum Triglycerides and cholesterol Reduces OC efficacy. Use other method. Sedatives, Hypnotics – Induction of hepatic microsomal enzymes For short course use additional method. For long course use higher dose of OC or other method. Antacids – Decrease intestinal absorption of Progestin Dose 2 hours apart. Antihistamine, Analgesics, Antimigraine, Vitamin E – Reduced OC efficacy reported. Folic Acid – OC may impair folate metabolism Increase dietary intake or supplement. Vitamin B12 – Reduces serum Vitamin B12 Increase dietary intake or supplement. Alcohol – Possible increased level of Ethanol or acetaldehyde Use with caution. Anticoagulants – OC increases clotting factors Decrease efficacy May potentiate in some Use another method. Antidiabetic Drugs – OC may impair glucose tolerance and increase blood glucose. Use low dose EE and progestin OC. Monitor blood glucose or use other method. Caffeine – Action of caffeine may be enhanced as OC may impair hepatic metabolism of caffeine. Herbal Preparations including St. John’s Wort – Degradation of contraceptive steroids, Decreased effectiveness of EE, Breakthrough bleeding or OC failure. Serious Adverse Reactions: Thrombophlebitis, Pulmonary Embolism, mesenteric thrombosis, retinal thrombosis, cerebral thrombosis, cerebral hemorrhage, myocardial infarction, hypertension, benign hepatic tumour and gall bladder disease. Thromboembolic complications – post surgery there is an increased risk in OC users after major surgery. OC should be discontinued one month prior to surgery and alternative methods used. OC should not be resumed until the first menstrual period after hospital discharge. Question: If I prescribe an OC with 20 ug of EE is there a greater risk of spotting? Spotting is common in the first few months which stops spontaneously in most within 3 months. There is no conclusive data indicating less cycle control with an OC with 20 ug of EE than with OCs containing 30-35 ug EE. Products containing levonorgestral or norgestrol are associated with lower incidence of breakthrough bleeding than those containing norethindrone either monophasic or triphasic. Given that there is no combine OC that is less likely to cause metrorrhagia, it appears reasonable to start with the lowest dose recommended by Health Canada, The FDA, and the WHO. Take the pill at the same time every day. Absorption problem with diarrhea or vomiting. Is she taking Anticonvulsants or Rifampin; heavy smoking which can unduly increase metabolism of the pill. Question: Does the pill increase the risk of cancer? A) Breast Cancer – The risk of breast cancer in former users is minimal. Breast cancer increases with age and effect of OC can be felt up to 10 years after stopping the pill. B) Ovarian and Endometrial Cancer – 30-50% reduction. C) Cervical Cancer – Controversial due to risk factors related to sex (condom use, age at first intercourse, number of partners, etc.). Pap test is indicated at the annual follow-up of OCs. D) Liver Cancer – OC could increase the risk of liver cancer. Very rare. 2 cases in 100,000 women. Benign hepatic adenoma may also occur rarely. Question: What to do if one or several pills are missed? Recommendations from Contraceptive Technology: 1,2,3 or 4 pills missed in the first few days – take two pills as soon as possible then take the rest of the pack as usual. But, if 2-4 pills are missed in the third week – discard the rest of the pack and start a new pack of pills. If patient had sex in the 5 days before forgetting to take pills – advise Plan B emergency contraception and condom, then start her pills from a new pack with no time off. Pregnancy Termination Elective and Therapeutic Abortion Early in pregnancy (less than 49 days) both medical and surgical may be used. Medical - Mifepristone (an antiprogestin) can be administered and Misoprostol (a prostaglandin) to induce uterine contractions expelling products of gestation. Effective in 96% of cases. Methotrexate – can be used but takes longer. Both sometimes require completion of evaluation by D&C. Surgical – Risks – hemorrhage, infection, perforation, anaesthetic Aspiration with manual or mechanical suction curettage is more than 99% effective after cervical dilatation has been achieved with Misoprostol or Laminaria tents. No long term adverse effects on reproductive health. Short term – diarrhea, nausea, vomiting and diarrhea Second Trimester Abortion For 1. Serious genetic abnormality. 2. Intrauterine fetal death. Most commonly done by Prostaglandin or Misoprostol vaginal suppositories to induce contractions; oxytocin may or may not be required. Or D&E (dilatation and evacuation of fetus) – also may be needed with septic abortions. Preconception Counselling Should start before pregnancy ( organogenesis begins in early pregnancy and placental development starts with implantation at 7 days post conception). Most of the time this opportunity is missed. Half of all pregnancies are unplanned. Aim is to identify and modify biomedical, behavioural and social factors to women’s health. Components - a single visit is not enough. Risk assessment. Health promotion. Medical/psychosocial intervention and follow-up. Recommended for every woman in reproductive age. Opportunity to counsel and change dietary behaviour, health behaviours, healthy environments, medications use, infections and immunizations, genetic screening and family history, nutrition assessment, substance abuse, toxins and teratogens, psychosocial concerns. Medications: What and dose. Potential maternal benefits/risks to fetus. Herbs and supplements. Infections and Immunizations: Periodontal, Urogenital and STI TORCH (toxoplasmosis, other, Rubella, Cytomegalovirus, Herpes) Update immunization – Rubella, Hepatitis, Varicella, T-dap – combined tetanus, diphtheria and pertusis, HPV and influenza vaccine. Nutritional – BMI; biochemical (anaemia), dietary risks (too little, too much) Substance Abuse – smoking, alcohol, street drugs Physical Exam – Focus on periodontal, thyroid, heart, breasts and pelvic exam. Lab Tests – CBC, Urinalysis, blood type, screen Rubella, Syphyllis, Hep B, HIV, Pap smear, GC, Chlamydia. Diabetes in selected population and check TSH. Major – Family planning, healthy weight, multivitamins with folic acid, Health Behaviours – Nutrition, exercise, safe sex, contraception, dental care. Discourage risky habits – douching, non use of seatbelts, smoking, alcohol, substance abuse Ideal BMI – BMI < 19 are at a greater risk for low birth weight or premature infants BMI >29 are at a greater risk for obstetric complications, PIH, diabetes and fetal macrosomia Investigations and Therapeutic Options for a Couple with Infertility Younger age group – start investigations after 1 year of unprotected sex. Older women >35 years of age – start after 6 months. 80% of couples achieve conception within 1 year. Rate of Infertility – 15%> in general population Female factor – 50% Male Factor – 40% (scrotal injury, orchitis, prior pelvic, inguinal or genitor urinary surgery, radiation/chemotherapy, medications, marijuana, hypospodius, varicocele, tobacco, chronic disease, testicular atrophy, prostatitis, alcohol, epididymitis) No obvious etiology – 10% Multiple causes – 40% of couples Semen analysis – Volume 2 ml, count > 20 million/ml, motility 50%, morphology 50% normal, viability 50% or more live. WBCs – fewer than 1/10 Endocrine tests – LH, FSH, Testosterone, PRL Low LH, FSH – indicates hypothalamia – pituitary failure Prolactin – prolacinemia FSH produces substantial parenchymal damage to pituitary Treatment – Male – sex 1-2 days in peri-ovulatory phase Lubricant – to be non-toxic. No smoking/alcohol. No sauna, hot tub, tight underwear Low semen count or volume – IUI Lower sperm density – HMG (human menopausal gonadotrophin) Hyerprolactinemia – bromocriptine Decreased semen quality – look for variococele IVF – is an effective treatment for male factor with ICSI. Treatment – Female – Ovulation tests – regular 22-35 day cycles mean ovulatory LH – serial measurement of urinary LH Progesterone – mid luteal phase, normal 5-40 ng/ml BT chart – slight rise followed by fall even if 1o temp. Endometrial biopsy – have been abandoned. Use of fertility drugs – eg Clomiphene Citrate or gonadotrophin will correct luteal phase insufficiency Pituitary insufficiency – injection of hmg (contains FSH and LH) Hyperprolactinemia – even very subtle - >10 units – try Bromocriptine Treatment – Female continued… P.C.O.S. – Clomiphene – an orally active antiestrogen 50 mg x 5 days – chronic mild suppression of FSH increase both ovarian and adrenal androgen production, clomiphene inhibits negative feedback effect of endogenous E2 – rise in FSH and stimulates follicular maturation. Insulin resistance – Metformin, increase insulin sensitivity is being used more and more with or without Clomiphene. Laparoscopic Ovarian Drilling – by cautery/laser. Main complication of ovulation induction – ovarian hyperstimulation syndrome - ovarian enlargement with ascites (fluid and protein) - use Clomiphene in graduated doses – 50 mg to 75 to 100 Multiple pregnancy rate – 5 to 8% with less than 1% exceeding twins With HMG – 20 to 30% rate of multiple pregnancy Cervical Factor – Post coital test – has more or less been abandoned. - Cervical infection – Doxycycline 100 mg BID x 10 days for both partners Uterine or Tubal Factors – Do HSG/hysteroscopy. HSG outlines both. Uterine – submucous fibroid, endometrial polyp are seldom the cause of infertility, may be associated with first trimester abortion. Tubal occlusion – due to prior salpingitis. Laparoscopy with dye and HSG – fimbria – most common. Microsurgical Tuboplasty – success rate 60 – 80% About 10% will be ectopic after tubal surgery. Peritoneal Factor – laparoscopy Endometriosis – 30 to 50% of infertile women Peri-adnexal adhesions – affecting tubal motility Tubal factor - success rate low <30% Assisted Reproductive Technology – A.R.T. IVF – Intracytoplasmic sperm injection (ICSI) High success rate – 30 to 35% Embryo transfer Egg Donation from Donor - Higher success rates than regular IVF (about 40%) Recipient to be programmed for optimal uterine receptivity by replacement doses of Estrogen and Progestin, to be continued until the placenta takes over in the late first trimester. Excellent success rate of egg donation mandates conservation of the uterus when future fertility is desired even if ovaries must be removed. Overall success rate by all methods combined 50 to 60% of infertile couples.
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