Vasiliki A. Moragianni, MD, MS REI CREOG REVIEW Vasiliki A. Moragianni, MD, MS Ben Lannon, MD Laura Smith, MD January 8, 2010

Microbiology/Immunology Menstrual abnormalities Vasiliki Moragianni

Most appropriate pharmacologic mgmt is: 39yo who smokes cigarettes consults you for severe irritability and poor concentration. Prospective sx calendar (kept for previous 3 menstrual cycles): sx are cyclic, occur 10 days before + resolve within 2 days of onset of menses. Mood and cognitive changes interfere with work performance. Has not responded to caffeine restriction, exercise, dietary supplements. Most appropriate pharmacologic mgmt is: Buspirone hydrochloride (BuSpar) in luteal phase Depot medroxyprogesterone acetate injections GnRH agonist therapy SSRI in luteal phase Spironoloctone (Aldactone) in luteal phase Q. 77 (Office)

PMS-PMDD >1/3 of menstruating women, mostly >30yo  in serotonergic function after ovulation If PMS is severe + functional impairment = PMDD Dx: Limited to luteal phase Mood, physical, cognitive sx Impairment Not explained by other dx (thyroid…)  check TSH Prospective sx charting Tx: OCPs: 24/4 of 20mcg ethinyl estradiol + 3mg drospirenone = YAZ ® Not if >35yo and smoker! SSRIs: Fluoxetine, Paroxetine, Sertraline Cyclic, if fails continuous ONLY if these fail Anxiolytics (BuSpar) Depot GnRH agonists

The most appropriate next step in management is: Visual field 36yo G2P2 p/w amenorrhea for past 6 years. Medical hx significant for dx of paranoid schizophrenia, which is well controlled with medication. Current meds include haloperidol decanoate (Haldol), benztropine mesylate (Cogentin) and lorazepam (Ativan). Exam unremarkable except for galactorrhea from L breast. Labs normal except for elevated serum prolactin of 142 ng/mL. MRI of pituitary shows no evidence of tumor. The most appropriate next step in management is: Visual field Reduce antipsychotic medications Mammography DXA scan Q. 32

Increased generalized adiposity Skin hypopigmentation Acral changes 32yo G2P2 p/w amenorrhea x 1year. Labs: FSH 3 mIU/mL, TSH 2.1 μU/mL, PRL 55 ng/mL. As you consider additional laboratory testing you perform a directed physical examination to look specifically for: Reduced body hair Increased generalized adiposity Skin hypopigmentation Acral changes Exophthalmos Q. 22

The best next step in the management is: Pituitary function testing 37yo G1P1 p/w amenorrhea and galactorrhea x 2 years. She reports increasingly severe frontal headaches over this period. Labs: FSH 21 mIU/mL, TSH 2.6 μU/mL, PRL 46 ng/mL. The best next step in the management is: Pituitary function testing Formal visual field testing Pelvic u/s MRI of sella turcica Treatment with dopamine agonist Q. 84

25yo G0 p/w lethargy, constipation, cold intolerance, breast discharge 25yo G0 p/w lethargy, constipation, cold intolerance, breast discharge. HR 55bpm, B/L galactorrhea. PRL 67 ng/mL, TSH 15 μU/mL. The hormone responsible for prolactin elevations and galactorrhea in this pt is: IGF-1 TRH Free T4 TSH Vasopressin Q. 71

The most appropriate next step in mgmt is: Clomiphene citrate 28yo p/w h/o infrequent menses. LMP 4 months ago. BMI 26, B/L galactorrhea. Labs: neg hCG, nl TSH, DHEAS 180 μg/dL, fasting PRL 75 ng/mL. Repeat PRL still elevated. MRI of pituitary: nl. The most appropriate next step in mgmt is: Clomiphene citrate Dexamethasone Wgt reduction Metformin Bromocriptine mesylate Q. 111

Hyperprolactinemia Physiologic processes: Pharmacologic causes: Pregnancy Breastfeeding, nipple stimulation Sleep Hypoglycemia Stress Exercise Orgasm Pharmacologic causes: Dopamine antagonists Monoamine oxidase inhibitors

Hyperprolactinemia Associated conditions: PCOS Cushing’s CNS lesions Centripetal obesity Moon facies Buffalo hump Acne Mucocutaneous fungal infections (tinea versicolor) Hyperpigmentation CNS lesions GH secreting tumor 40’s Co-secrete GH + PRL Acromegaly, oily skin, hyperhydrosis Craniopharyngioma (bimodal distribution) Hypothyroidism (# 1 endocrinopathy in pt’s with hyperprolactinemia) Myxedema (not exophthalmos): rare finding of late dz

Hyperprolactinemia Antipsychotics  antidopaminergic action within mesolimbic system: carries over to D2-R located in pituitary lactotrophs Usually PRL >100 ng/mL Sx: galactorrhea, amenorrhea, oligomenorrhea, sexual dysfunction, infertility, hirsutism, acne, vaginal atrophy Dx: MRI of sella turcica (r/o prolactinoma) Get DXA scan (prolonged hypoestrogenic state) Antipsychotic AND bromocriptine: exacerbates psychotic sx!!! Newer antipsychotics (little/no effect on prolactin): olanzapine (Zyprexa), clozapine (Clozaril), quetiapine (Seroquel)

TRH = prolactin-releasing factor Thyroid axis: + by TRH ( TSH, PRL) - by somatostatin, dopamine

Gonadotrope adenomas Levels frequently  paradoxically in response to TRH-stimulation test < 10mm (microadenoma): observation Repeat MRI if sx Visual fields yearly > 10mm (macroadenoma) or sx: transsphenoidal surgery Sometimes respond to dopamine agonist / octreotide (inhibits GH)

Rx Bromocriptine: Start: 1.25 – 2.5 mg QD Therapeutic: 5-7.5 mg QD Max: 10-15 mg QD (2-3 divided doses) Side effects: GI (minimized if PV) Cabergoline: Start: 0.25 mg 2x/wk Max: 1 mg 2x/wk Fewer side-effects

FSH receptor gene mutation 17α-hydroxylase deficiency 28yo G0 developed premature ovarian failure @ 22yo and 46,XX premature ovarian failure was diagnosed. Her older sister developed the same condition @ 31y/o. At l/s for pelvic pain, found to have very small round ovaries measuring 1 cm bilaterally. Before considering her youngest sister as an oocyte donor, the pt should be screened for which one of the following causes of familial ovarian failure: Swyer syndrome Galactosemia Fragile X premutation FSH receptor gene mutation 17α-hydroxylase deficiency Q. 35

POI Menopause <= 40yo (2 s.d.) Workup: Other genetic disorders: karyotype FMR1 premutation gene Other genetic disorders: Resistant ovary syndrome (Savage) - ? Mutation in FSH-R 17α-hydroxylase deficiency Associated with other autoimmune endocrine disorders Hashimoto’s thyroiditis Hypoparathyroidism Adrenal insufficiency Pernicious anemia Swyer (46,XY), Turner’s (45,X): streak gonads, no puberty

The most appropriate treatment regimen for this pt is: GnRH agonist 18yo with AML is scheduled to undergo high-dose chemo and total body XRT for bone marrow transplant in 5 days. Her hematologist requests advice regarding the best approach to conserve ovarian function and to reduce the likelihood of vaginal bleeding during the anticipated chemo-induced pancytopenia. The patient has regular menses and her LMP was 6 days ago. She is not using contraceptives. The most appropriate treatment regimen for this pt is: GnRH agonist Depot medroxyprogesterone acetate Combination OCPs GnRH antagonist Transposition of the ovaries Q. 67

(or less if started in luteal phase) GnRH agonists GnRH antagonists Initial Flare ( FSH, LH) YES NO ( chemo pt’s) FSH, LH downregulation 10-14 days (or less if started in luteal phase) hours Examples Lupron Ganirelix, Cetrorelix

16yo adolescent comes in for evaluation of 1o amenorrhea + lack of breast development. Denies being sexually active, no h/o VB. Hgt is 134.6cm (53in), Tanner I breasts, Tanner I pubic hair, nl vaginal length, visible cx, small palpable uterus, no palpable ovaries. Initial labs: neg serum preg test, nl Prl, nl TSH. The serum measurement that would povide the most information to make the dx is: FSH Estradiol Testosterone DHEAS 17-OH-progesterone Q. 117

1o amenorrhea r/o outflow tract disorders Serum hCG, FSH, PRL, TSH Pelvic u/s (+ ovaries, - uterus = müllerian agenesis) 20% of cases caused by congenital abnl PAIN Serum hCG, FSH, PRL, TSH High FSH = hypergonadotropic hypogonadism  karyotype 45X/46XY, 46XY gonadal dysgenesis (Swyer)  surgical gonadal removal Low FSH = hypogonadotropic hypogonadism  CT / MRI of head Lack of breasts = low E Sx of hyperandrogenism: T, DHEAS, 17-OH-P

The most appropriate next diagnostic test for this pt is: 33yo for evaluation of 1o infertility. Good health, nl menses. Initial labs: nl FSH, nl LH. PRL 31 ng/mL. TSH 4 µU/mL, free T4 1.1 ng/dL. The most appropriate next diagnostic test for this pt is: T3 concentration Repeat TSH concentrations TRH stimulation test Pituitary MRI Thyroid u/s Q. 78

Thyroid testing Mildly elevated TSH, nl T4 TRH stimulation test Subclinical hypothyroidism Recovery from nothyroidal dz Late evening Adrenal unsufficiency Rx (Reglan, Motilium) TSH-secreting pituitary adenomas TRH stimulation test Not useful, ? in pt’s with untreated central hypothyroidism

Hyperinsulinemia and hyperthecosis 57yo, 6 years postmenopausal, p/w new-onset hirsutism and increased sensitivity and size of the clitoris. Nl BP, increased muscle mass, no HTN, no acanthosis nigricans, no adnexal mass, no striae. Pelvic u/s reveals nl ovaries, CT shows nl adrenals. Serum T level is 300 ng/dL. The most likely dx is: Adult onset CAH Adrenal tumor Hilus cell tumor Cushing’s syndrome Hyperinsulinemia and hyperthecosis Q. 45

You recommend for tx of her hirsutism: GnRH agonist (Lupron) Flutamide 29yo requests alternatives to OCPs to treat her long-standing abnl facial hair growth. She has used OCPs for control of acne and facial hair growth for the past 9 years but is not satisfied with the results. You recommend for tx of her hirsutism: GnRH agonist (Lupron) Flutamide Ketoconazole (Nizoral) Spironolactone Q. 123

The next best step in mgmt is to continue OCPs and prescribe: 19yo Hispanic women with h/o hepatitis comes in for mgmt of hirsutism present since puberty that has become more severe despite tx with OCPs. Dark facial hair on the sides of her face, upper lip and chin. No acanthosis nigricans, no clitoromegaly. DHEAS, serum T, androstenedione levels are at upper limits of nl. TSH nl, PRL nl. Basal 17-OH-P level is 230 ng/dL. Following administration of contricotropin, her 17-OH-P level increases to 510 ng/dL. The next best step in mgmt is to continue OCPs and prescribe: Flutamide Spironolactone Finasteride GnRH agonist Q. 28

Hirsutism Testosterone production in women: 25% from ovary (↑ with LH, IGF-1, i.e. PCOS) – u/s T >200 in premenopausal, >100 in postmenopausal  ovarian tumor (hilus cell) 25% from adrenals - CT 50% from peripheral conversion Basal 17-OH-P > 200  adrenal stimulation test Administer IV ACTH Check 17-OH-P 30-60 min later: If >1,000 = nonclassic CAH

Rx Flutamide Androgen-R antagonist, used in prostate CA Liver toxicity, feminization of male fetus Finasteride 5α-reductase inhibitor, used in BPH Least side effects, feminization of male fetus Ketoconazole Inhibits cytochrome P450 Liver toxicity, warfarin potentiation Spironolactone Aldosterone antagonist, structurally related to progestins  inhibits steroidogenesis, androgen antagonist, inhibits 5α-reductase activity Hypotension, hyperkalemia (rare with nl renal fxn), feminization of male fetus OCPs + spironolactone >> spironolactone

The most appropriate tx for this pt is: OCPs Lupron for 3-6 months 44yo who smokes 1 ppd, h/o heavy menses. Menses are regular, last 8 days, heavy for 5 days with intermittent passage of small clots. Saline infusion u/s showed slightly enlarged anterior-posterior diameter and nl endometrial cavity. Pap test and cervical cx neg. EMB showed secretory endometrium. No immediate interest in fertility. The most appropriate tx for this pt is: OCPs Lupron for 3-6 months Depot medroxyprogesterone acetate Levonorgestrel IUD Q. 90

The most common pathophysiologic basis for her disorder is: 13yo for evaluation and tx of rapid wgt gain and irregular menses. FHx of obesity, DM in her father and endo in her aunt. Morbidly obese, + acanthosis nigricans. Waist circumference is 90 cm, fasting blood glc is 175, total cholesterol is 300. The most common pathophysiologic basis for her disorder is: Hyperlipidemia Hypothalamic dysfunction Hyperandrogenemia Insulin resistance Leptin gene mutation Q. 40

Metabolic syndrome Need 3 for dx: Central obesity – waist circumference > 88cm in women, > 102cm in men ↑ TG (150) ↓ HDL (50 in women, 40 in men) ↑ BP (130/85) ↑ fasting glc (110)

Infertility & Menopause Ben Lannon

Which is the correct method to perform a Clomid Challenge Test: Administer 100mg CC day 3-7. Sample FSH on day 3 and 10. Administer 50mg CC day 5-9. Sample FSH on day 5 and 10 Administer 100mg CC day 5-9. Sample FSH on day 3 and 10 Administer 100mg CC day 3-7. Sample FSH on day 5 and 10.

Which of the following is the correct interpretation of a CCCT: The FSH declines from day 5 to 10, implying normal ovarian reserve The FSH increases from day 5 to 10, implying decreased fecundability An elevated FSH on either day implies diminished ovarian reserve An elevated FSH on either day implies the patient should use gonadotropins instead

Clomiphene Challenge Test More sensitive test of ovarian reserve than D3 FSH alone CC should cause a transient increase in FSH/LH but should be suppressed by D10. Fewer follicles produce less inhibin and less negative feedback inhibition of CC induced FSH rise. Thus FSH is elevated at D10. Elevated FSH (>15) on D3 or 10 implies poor response to exogenous stimulation. D3 E2 >80 also a poor prognosis

In patients using CC for ovulation induction, the frequency of twinning is: < 1% 5-10% 15-20% 25-30% 35-40%

Multiples with Clomid Twins: 6.9 to 9% Triplets: 0.3 to 0.5 % Quadruplets: 0.3 % Quintuplets: 0.13%

Which of the following is the most significant side effect of Clomiphene Hot flushing Visual disturbances Mood swings Ovarian hyperstimulation Head aches

CC side effects Hot flashes 10-20% Ovarian enlargement – 14% OHSS – rare Visual symtoms – blurring, doiplopia, sotomata may be irreversible and are indication to discontinue treatment Mood swings, depression, headache – typically mild and transient

A 28yo G0 is undergoing CC treatment for anovulation A 28yo G0 is undergoing CC treatment for anovulation. Initial findings are shown. Basal body temps are monophasic with 50mg of CC on days 5 to 9. The next most appropriate step in management is: Repeat cycle with 50mg CC on days 3 to 7 Add metformin 500mg BID Administer hCG on day 16 of the cycle Add intrauterine insemination Increase CC to 100mg FSH d3 4.3 E2 d3 54 PRL 15 ng/ml Total motile sperm: 27 million HSG: normal

Clomiphene management Increase dose up to mg until ovulation is achieved – positive urinary LH or biphasic BBT Can give days 3-7 or 5-9. Earlier theoretically provides shifts LH/FSH balance earlier in cycle but no proven difference. Metformin may have some role in PCOS but not anovulation IUI increases pregnancy rates slightly but won’t help without ovuluation

She has normal ovulatory function She has adequate ovarian reserve A 27yo G0 is undergoing infertility evaluation. Her LMP was 15 days prior. Pelvic exam reveals copious clear, elastic cervical mucus. Which of the following is true? She has normal ovulatory function She has adequate ovarian reserve She is producing an effective amount of estrogen She has a luteal phase defect She is producing adequate progesterone

Cyclic cervical changes E2 peaks prior to ovulation and stimulated cervical glands – mucus is clear, watery, stretchy (spinnbarkeit) After ovulation – progesterone changes cervical gland production to thick, viscous mucus

Initiation of weight loss program Reduce caffeine A sedentary 32yo woman with BMI 28 consumes 1 glass of 1 wine and 3 cups of coffee daily. She smokes 1PPD. The change in lifestyle that would most affect her success rate with IVF is: Initiation of weight loss program Reduce caffeine Initiate a low fat diet Stop smoking Reduce alcohol

Lifestyle effects on fertility Smoking – 30% reduction in pregnancy rate, 40% reduction in eggs BMI, alcohol, caffeine have more modest effect

Which of the following is an indication for ICSI: Sperm count of 5 million per mL Sperm motility of 50% Semen volume of 0.5 cc Strict morphology of 8% normal

ICSI indications Normal semen parameters 20 million/mL >50% motile >4% normal forms ICSI for male factor less than 10 million/mL Other indications – failed fertilization, unexplained infertility, poor egg quality, PGD,

Y chromosome microdeletion 32yo male with normal gonadotropins has severe oliogospermia. Which of the following conditions would affect 100% of male offspring if they underwent ICSI. Y chromosome microdeletion Cystic fibrosis trasmembrane regulator - CFTR mutation Premature testicular failure Congenital bilateral absence of the vas deferens - CBAVD

Genetics of oligospermia 5-15% chromosomal abnormalities 47 XXY most common Y microdeletions 10-15% azospermia, 3-10% oligo 10-15% CBAVD 60% associated with CFTR – autosomal recessive Premature gonadal failure – elevated gonadotropins, low T No known genetic predisposition

For each patient with azoospermia select the most likely diagnosis 29yo man with adrenal insufficiency at age 2 and hypogonadism at age 15 Klinefelters Laurence-Moon Idiopathic hypogonadism Kallmans GnRH-R mutation DAX-1 mutation FSH-R mutation

For each patient with azoospermia select the most likely diagnosis Healthy 32yo with complete pubertal development and FSH 4, LH 2, total T 60 ng/dL Klinefelters Laurence-Moon Idiopathic hypogonadropic hypogonadism Kallmans GnRH-R mutation DAX-1 mutation FSH-R mutation

For each patient with azoospermia select the most likely diagnosis 28yo male taller than predicted height with reduced lean body mass and scanty pubic hair. FSH 24, T 98, FBG 145 Klinefelters Laurence-Moon Idiopathic hypogonadropic hypogonadism Kallmans GnRH-R mutation DAX-1 mutation FSH-R mutation

For each patient with azoospermia select the most likely diagnosis 32yo scandanavian male with normal exam, reduced testicular size. A sister had POF at age 19. A brother also has low sperm count. Klinefelters Laurence-Moon Idiopathic hypogonadropic hypogonadism Kallmans GnRH-R mutation DAX-1 mutation FSH-R mutation

Differential of hypogonadism Usually present with delayed puberty Low testosterone – normal male ~500-600 Hypogonadotropic GnRH R mutation rare KAL - X-linked – anosmia, Dax-1 – X-linked – development of adrenal cortex and hypothalamus/pituitary Present with AI (adrenal precursors not elevated) Can survive with corticosteroid replacement Laurence-Moon – rare Hypergonadotropic Klinefelters – most common – tall, hypogonadal, 47 XXY or mosaic 46 XY/47 XXY. FSH R mutation - Finland

Menstrual history and symptoms Basal body temp charting 46yo presents with 9 mo of irregular menses. She has hot flushes and sleep disturbance. Pelvic exam is normal. The most appropriate way to diagnose menopause in this patient is: Serum FSH Serum LH Serum E2 Menstrual history and symptoms Basal body temp charting

Dx of menopause 12 months after last period FSH is often elevated but can be highly variable. Not diagnostic. Can see hyper or hypoestrogenic state depending on timing BBT can document ovulation but not menopause

Combined hormone therapy Transdermal estrogen patch 45 yo nonsmoker presents with menorrhagia over the past 6 months then a skipped cycle. HCG is neg and EMBx is normal. She also reports mild hot flushes, night sweats, mood lability. She requests hormonal intervention. Which is most appropriate: Combined hormone therapy Transdermal estrogen patch Low-dose combined OCP Monthly 10 day course of MPA Hormonal therapy is not indicated for these symptoms

Treatment of perimenopause FSH is elevated due to reduced inhibin Erratic release of FSH results in erratic E2 Post menopause HRT is insufficient dose MPA alone may control bleeding but not vasomotor symptoms E2 patch should not be unopposed Combined low dose OCP should control bleeding and suppress FSH and E2 variability and protect endometrium OCPs are no longer contraindicated by age alone

Progestin releasing IUD diaphragm 41 yo with irregular vaginal bleeding, hot flushes, and dyspareunia is primarily concerned about contraception. She smokes 1 PPD and has a hx of depression. She is attempting to loose weight and exercise. Which is most appropriate: Combined OCP Progestin only pill Depot MPA Progestin releasing IUD diaphragm

Perimenopausal contraception OCPs are not a first choice for smokers >35 Diaphragm has high failure rate ~16% POP has failure rate ~8% DMPA has 3% failure rate but associated wgt gain Progestin IUD has low (<1%) failure rate and low risk of side effects. Will not control vasomotor sxs.

Clonidine Megestrol acetate SSRI Premarin Black cohash 42yo P1 presents with severe hot flushes, insomnia, fatigue, and irritability over 2 months. She is s/p wide local excision and chemo for ER/PR neg breast cancer. Menses became irregular following chemo. Exam is nl. Labs notable for elevated FSH and low E2. Which is the next step in management: Clonidine Megestrol acetate SSRI Premarin Black cohash

Hormonal alternatives Estrogen (90% reponse) and progesterone (80%) can alleviate hot flushes but are not first line in breast cancer (despite receptor status) Clonidine (30%) SSRI – effexor/paxil (50%) Black cohosh similar to placebo

For each menopausal patient with vasomotor sxs select the best test prior to starting HRT (assume normal mammo, normal lipids 2 years prior) 54 year old hispanic P3 with T2DM, mild obesity, and smokes 1-2 PPD. DXA Lipid profile Fasting glucose BRCA1 FSH

For each menopausal patient with vasomotor sxs select the best test prior to starting HRT (assume normal mammo, normal lipids 2 years prior) 48yo causaian P0 who exercises regularly. Her mother and maternal aunt had breast cancer prior to 45 DXA Lipid profile Fasting glucose BRCA1 FSH

For each menopausal patient with vasomotor sxs select the best test prior to starting HRT (assume normal mammo, normal lipids 2 years prior) 50yo AA P2 with history of asthma requiring periodic steroid use DXA Lipid profile Fasting glucose BRCA1 FSH

Screening prior to HRT HRT may have some benefit on lipids HRT is not for primary or secondary prevention of cardiovascular disease FH of breast cancer is not a contraindication unless a known carrier of BRCA1 Strong family history of early onset Postmenopausal steroid users are at increased risk of osteoporosis. FSH is not indicated

REI Procedures Pediatric and Adolescent Gyn Laura Smith

1. A patient with longstanding infertility undergoes HSG, which shows bilateral proximal tubal occlusion. In the proximal tube, there is a honeycomb pattern of contrast that seems to enter the tube wall. Subsequent laparoscopy shows multiple 1-2cm nodules in the isthmus of one fallopian tube. The most likely diagnosis is: (A) chronic chlamydial salpingitis (B) tuberculous salpingitis (C) salpingitis isthmica nodosa (D) prenatal exposure to diethylstilbestrol (E) ectopic pregnancy

1. A patient with longstanding infertility undergoes HSG, which shows bilateral proximal tubal occlusion. In the proximal tube, there is a honeycomb pattern of contrast that seems to enter the tube wall. Subsequent laparoscopy shows multiple 1-2cm nodules in the isthmus of one fallopian tube. The most likely diagnosis is: (A) chronic chlamydial salpingitis (B) tuberculous salpingitis (C) salpingitis isthmica nodosa (D) prenatal exposure to diethylstilbestrol (E) ectopic pregnancy

Salpingitis isthmica nodosa (Prolog p. 90) Single / multiple outpouchings / diverticulae of fallopian tube often bilateral, often multifocal, so surgery not always works IVF = treatment of choice Infection  prox obstruxn, distal obstruxn, hydrosalpinx, or normal HSG TB  nodular thickening of tubes DES  T shaped uterus, tubes often patent

(A) spontaneous abortion (B) fetal anomalies from radiation 2. A 25yo G3P0 with a h/o PCOS comes in for evaluation of recurrent SAB. She reports a history of irregular menses ranging in length from 35-90 days. She undergoes HSG on day 8 of her cycle after 3 days of light flow. After injection of dye, an intrauterine filling defect is seen. A pregnancy test is positive. The most important complication to discuss with her is: (A) spontaneous abortion (B) fetal anomalies from radiation (C) pelvic infection (D) hemorrhage (E) intrauterine adhesions

(A) spontaneous abortion (B) fetal anomalies from radiation 2. A 25yo G3P0 with a h/o PCOS comes in for evaluation of recurrent SAB. She reports a history of irregular menses ranging in length from 35-90 days. She undergoes HSG on day 8 of her cycle after 3 days of light flow. After injection of dye, an intrauterine filling defect is seen. A pregnancy test is positive. The most important complication to discuss with her is: (A) spontaneous abortion (B) fetal anomalies from radiation (C) pelvic infection (D) hemorrhage (E) intrauterine adhesions

Complications of HSG (Prolog p. 100) At BIVF, performed CD5-12. Prolog says “2-5days after cessation of menstrual flow.” goal timing = thin endometrial lining (minimize false + tubal obstruxn) and not pregnant if irregular menses, do UPT prior to HSG One study: SAB rate 50% after HSG in pregnant patients No increased risk congenital anomalies For pregnancies dx at HSG, abortion not recommended

(A) 17 years (B) 20 years (C) 26 years (D) 35 years (E) 38 years 3. A 44yo Chinese-American woman is considering using an oocyte donor because of her age. The preferable age of the donor is: (A) 17 years (B) 20 years (C) 26 years (D) 35 years (E) 38 years

(A) 17 years (B) 20 years (C) 26 years (D) 35 years (E) 38 years 3. A 44yo Chinese-American woman is considering using an oocyte donor because of her age. The preferable age of the donor is: (A) 17 years (B) 20 years (C) 26 years (D) 35 years (E) 38 years

Informed consent for donor eggs (Prolog p. 105) ASRM has guidelines for oocyte donation ASRM recommends donors age 21-34 years Younger donors “can” donate, but they should have attained their state’s age of legal majority On the basis of age, the 26yo is preferable to the 35yo (younger eggs  decreased SAB rate / aneuploidy) ASRM recommends that the recipients be specifically informed if donor > 34yrs due to increased risk of aneuploidy

(A) premature menopause at age 35 years 4. In counseling patients on the use of donor oocytes, it is important to inform them of a substantially increased risk of maternal death during pregnancy if their ovarian failure is associated with: (A) premature menopause at age 35 years (B) natural menopause at age 50 years (C) bilateral oophorectomy for stage IV endo (D) Turner’s syndrome (E) Fragile X gene premutation

(A) premature menopause at age 35 years 4. In counseling patients on the use of donor oocytes, it is important to inform them of a substantially increased risk of maternal death during pregnancy if their ovarian failure is associated with: (A) premature menopause at age 35 years (B) natural menopause at age 50 years (C) bilateral oophorectomy for stage IV endo (D) Turner’s syndrome (E) Fragile X gene premutation

IVF in patients with Turner’s Syndrome (Prolog p. 119) Maternal mortality est. 2% in pts with Turner’s Aortic dilation, dissection, rupture in pregnancy Risk factors: bicuspid aortic valve +/- stenosis, regurg, or both 15% initiate puberty, 5% menstruate (variable time), 1% spontaneous pregnancy Maternal mortality est. 5% (normal aorta)-50% (affected aorta) in Marfan syndrome

(B) serum 17-OHP to evaluate for congenital adrenal hyperplasia 5. A 16yo with no history of sexual activity is being evaluated for primary amenorrhea. On PE, she has Tanner IV breasts, Tanner II pubic hair, a 2cm blind vaginal pouch, no visible cervix, and no palpable uterus or ovaries. Labs: FSH 8.3, testosterone 811 ng/dL. The best next step is: (A) pelvic ultrasound to evaluate for Meyer-Rokitansky-Kuster-Hauser syndrome (B) serum 17-OHP to evaluate for congenital adrenal hyperplasia (C) serum DHT level to evaluate for 5 reductase deficiency (D) karyotype to evaluate for complete androgen insensitivity

(B) serum 17-OHP to evaluate for congenital adrenal hyperplasia 5. A 16yo with no history of sexual activity is being evaluated for primary amenorrhea. On PE, she has Tanner IV breasts, Tanner II pubic hair, a 2cm blind vaginal pouch, no visible cervix, and no palpable uterus or ovaries. Labs: FSH 8.3, testosterone 811 ng/dL. The best next step is: (A) pelvic ultrasound to evaluate for Meyer-Rokitansky-Kuster-Hauser syndrome (B) serum 17-OHP to evaluate for congenital adrenal hyperplasia (C) serum DHT level to evaluate for 5 reductase deficiency (D) karyotype to evaluate for complete androgen insensitivity

Androgen insensitivity syndrome (Prolog p. 143) Incidence: 1/20,000 dx: phenotypic female, primary amenorrhea, little or no axillary and pubic hair, no uterus, 46XY karyotype, serum testosterone characteristic of normal adult men may have abdominal testes, inguinal testes, or testes in labia majora lack of androgen tissue receptors  scant pubic/axillary hair (or out of proportion to breast development) female body habitus due to peripheral aromatization of androgens  estrogens

6. In the prior 16 yo patient, the next step in management is: (A) psychologic counseling (B) breast augmentation (C) estrogen therapy (D) vaginoplasty

6. In the prior 16 yo patient, the next step in management is: (A) psychologic counseling (B) breast augmentation (C) estrogen therapy (D) vaginoplasty

Androgen insensitivity syndrome (Prolog p. 143) Breasts: typically paucity of glandular tissue and small, pale areola. Rarely need augmentation Gonadal tumors do not develop until after puberty (rare b/f age 20), so delay gonadectomy until sexual maturation complete. Estrogen treatment indicated when gonadectomy performed after puberty or at the time of expected puberty if gonadectomy done prepubertally Psychological development is typically feminine Nonsurgical approaches to creation of a vagina preferred: dilators. Vaginoplasty should not be attempted until the patient is ready to be sexually active

(B) decrease oocyte recruitment (C) decrease embryo implantation 7. A 28yo G0 undergoes laparoscopy for infertility and pelvic pain. Two years ago she had a bilateral neosalpingostomy. Based on the intraoperative findings, you perform a bilateral salpingectomy in preparation for future IVF. The effect that hydrosalpinges would have during IVF is: (A) significantly increase the risk of pelvic infection after oocyte retrieval (B) decrease oocyte recruitment (C) decrease embryo implantation (D) slow the rate of embryonic cell cleavage

(B) decrease oocyte recruitment (C) decrease embryo implantation 7. A 28yo G0 undergoes laparoscopy for infertility and pelvic pain. Two years ago she had a bilateral neosalpingostomy. Based on the intraoperative findings, you perform a bilateral salpingectomy in preparation for future IVF. The effect that hydrosalpinges would have during IVF is: (A) significantly increase the risk of pelvic infection after oocyte retrieval (B) decrease oocyte recruitment (C) decrease embryo implantation (D) slow the rate of embryonic cell cleavage

(B) placement of an intrauterine balloon catheter 8. A 29yo with a history of recurrent pregnancy loss undergoes an operative hysteroscopy to incise a moderate-sized uterine septum. The procedure is uncomplicated and there is no evidence of uterine perforation. The most important step in the management in the postop period is: (A) placement of an IUD (B) placement of an intrauterine balloon catheter (C) oral estrogen for 2 weeks postop (D) oral contraceptives for 2 months postop (E) hysterosalpingography 1-2 months postop

(B) placement of an intrauterine balloon catheter 8. A 29yo with a history of recurrent pregnancy loss undergoes an operative hysteroscopy to incise a moderate-sized uterine septum. The procedure is uncomplicated and there is no evidence of uterine perforation. The most important step in the management in the postop period is: (A) placement of an IUD (B) placement of an intrauterine balloon catheter (C) oral estrogen for 2 weeks postop (D) oral contraceptives for 2 months postop (E) hysterosalpingography 1-2 months postop

Surgical therapy for septate uterus (Prolog p.155) Intrauterine balloon catheter has not been proven to reduce adhesions Estrogen or hormonal therapy has no apparent role after resection of an avascular septum (more useful after hysteroscopic LOA in Asherman synd b/c endometrium is damaged) No role for postop IUD Postop HSG recommended after 1-2 months to eval if septum resection is complete Residual septa < 1cm can be left in place, will not interfere with future fertility

(B) failed tubal reanastamosis (C) age of the spouse (D) CD3 FSH level 9. A 38yo G3P3 in a new relationship with a 32yo man comes in for fertility evaluation after a failed tubal ligation reversal that was done 18 months ago. The pt had CD3 FSH 5, normal HSG, and he had nl SA. She is interested in the IVF success rates given her tubal factor infertility. The factor most likely to predict IVF success is: (A) age of the patient (B) failed tubal reanastamosis (C) age of the spouse (D) CD3 FSH level

(B) failed tubal reanastamosis (C) age of the spouse (D) CD3 FSH level 9. A 38yo G3P3 in a new relationship with a 32yo man comes in for fertility evaluation after a failed tubal ligation reversal that was done 18 months ago. The pt had CD3 FSH 5, normal HSG, and he had nl SA. She is interested in the IVF success rates given her tubal factor infertility. The factor most likely to predict IVF success is: (A) age of the patient (B) failed tubal reanastamosis (C) age of the spouse (D) CD3 FSH level

BTL and future fertility (Prolog p.158) 3-5% who had BTL express regret and request reversal Female partner age has been shown consistently to have the most dramatic effect on pregnancy success after sterilization reversal as well as IVF

(E) 17-hydroxyprogesterone 10. A 16yo comes in for evaluation of primary amenorrhea and lack of breast development. She denies being sexually active. Height is 53 inches. She has Tanner I breasts, Tanner I pubic hair. Normal vaginal length, visible cervix, small palpable uterus, and no palpable ovaries. Initial lab eval: negative bHCG, normal PRL, normal TSH. The serum measurement that would provide the most information to make the diagnosis is: (A) FSH (B) estradiol (C) testosterone (D) DHEA-S (E) 17-hydroxyprogesterone

(E) 17-hydroxyprogesterone 10. A 16yo comes in for evaluation of primary amenorrhea and lack of breast development. She denies being sexually active. Height is 53 inches. She has Tanner I breasts, Tanner I pubic hair. Normal vaginal length, visible cervix, small palpable uterus, and no palpable ovaries. Initial lab eval: negative bHCG, normal PRL, normal TSH. The serum measurement that would provide the most information to make the diagnosis is: (A) FSH (B) estradiol (C) testosterone (D) DHEA-S (E) 17-hydroxyprogesterone

Primary amenorrhea (Prolog p.159) Absence of menses by age 16 Secondary = no menses x 3 cycles of previous cycle length or 6 months amenorrhea Need to determine level of problem: hypogonadotropic or hypergonadotropic amenorrhea to initiate algorithm (hypothal, pituitary, ovarian, outflow) you already know E2 is low by no breast development no evidence hyperandrogenism, so T4, DHEAS, 17-OHP not helpful no suspicion for androgen insensitivity given Tanner I breast and palpable cervix, uterus so T4 also not useful for that diagnosis

(C) formation of antisperm antibodies (D) uterine contractions 11. A 29yo woman comes in for intrauterine insemination (IUI) with her husband’s washed semen sample. The couple has unexplained infertility, and they have just completed their 4th IUI with CC treatment. Before her initial procedure, her cervical cultures were negative for gonorrhea/chlamydia. The most common consequence of IUI is: (A) acute salpingitis (B) anaphylactoid reaction to components in the media used to prepare the semen (C) formation of antisperm antibodies (D) uterine contractions (E) transmission of viruses into the uterine cavity

(C) formation of antisperm antibodies (D) uterine contractions 11. A 29yo woman comes in for intrauterine insemination (IUI) with her husband’s washed semen sample. The couple has unexplained infertility, and they have just completed their 4th IUI with CC treatment. Before her initial procedure, her cervical cultures were negative for gonorrhea/chlamydia. The most common consequence of IUI is: (A) acute salpingitis (B) anaphylactoid reaction to components in the media used to prepare the semen (C) formation of antisperm antibodies (D) uterine contractions (E) transmission of viruses into the uterine cavity

Complications of IUI (Prolog p.162) Uterine contractions are minimized by washing sperm to decrease prostaglandin concentration in semen There have been isolated reports of anaphylactoid reactions to media, but very rare Formation of antisperm antibodies has not been documented after IUI of washed sperm samples IUI used to treat patients with antisperm antibodies (sperm washed, seems to help) Sperm washing during IUI seems to decrease the transmission of viruses into the uterus Infection very rare following IUI

(A) repeat SA after a longer period of abstinence 12. A 39yo man with a 10yr h/o type 1 DM is referred for evaluation of an abnormal SA. He and his wife have 3 yr h/o infertility. Her eval has been normal. He has had 3 SAs in the past yr, each after 48-72hr abstinence. All had vol 0.1-0.3mL, sperm concentration 1-2 million/mL, normal motility, normal morphology. No dysuria, urethral discharge, radiation, testicular trauma. The next step in his evaluation is: (A) repeat SA after a longer period of abstinence (B) collect a postejaculate urine sample (C) testicular ultrasonography (D) testicular biopsy (E) GnRH stimulation test

(A) repeat SA after a longer period of abstinence 12. A 39yo man with a 10yr h/o type 1 DM is referred for evaluation of an abnormal SA. He and his wife have 3 yr h/o infertility. Her eval has been normal. He has had 3 SAs in the past yr, each after 48-72hr abstinence. All had vol 0.1-0.3mL, sperm concentration 1-2 million/mL, normal motility, normal morphology. No dysuria, urethral discharge, radiation, testicular trauma. The next step in his evaluation is: (A) repeat SA after a longer period of abstinence (B) collect a postejaculate urine sample (C) testicular ultrasonography (D) testicular biopsy (E) GnRH stimulation test

Retrograde ejaculation (Prolog p.171) Abstinence min 48 hours, max 7 days for SA Longer abstinence  decreased motility as fructose is used DM associated with retrograde ejaculation: peristaltic function of the vas deferens and closure of the bladder neck are affected by neuropathy retrograde ejaculation should be suspected if SA vol < 1mL can collect sperm from urine sample, urine pH and osmolarity are optimized for sperm survival by adjusting patient’s fluid intake and sodium bicarbonate (baking soda): 2 tbsp. the night before and 2 hrs before ejaculation

(A) 3-dimensional ultrasonography (B) repeat HSG (C) sonohysterography 13. A 30yo woman with primary infertility x 1year undergoes HSG which shows normal uterine cavity but bilateral proximal tubal obstruction at the uterotubal junction. The patient has no history of previous abdominal surgery, STDs, pelvic pain, or dysmenorrhea. She would prefer not to undergo surgery or anesthesia. An appropriate next step for examination of the fallopian tubes is: (A) 3-dimensional ultrasonography (B) repeat HSG (C) sonohysterography (D) office hysteroscopy

(A) 3-dimensional ultrasonography (B) repeat HSG (C) sonohysterography 13. A 30yo woman with primary infertility x 1year undergoes HSG which shows normal uterine cavity but bilateral proximal tubal obstruction at the uterotubal junction. The patient has no history of previous abdominal surgery, STDs, pelvic pain, or dysmenorrhea. She would prefer not to undergo surgery or anesthesia. An appropriate next step for examination of the fallopian tubes is: (A) 3-dimensional ultrasonography (B) repeat HSG (C) sonohysterography (D) office hysteroscopy

Occlusion of fallopian tubes (Prolog p.176) Proximal tubal obstruction seen on 15% of HSGs d/dx: acute/chronic salpingitis, salpingitis isthmica nodosa, cornual fibroid, PID, endometritis, prior ectopic, adenomyosis, tubal spasm SIS to identify pelvic fluid as confirmation of patent tubes has false + risk of dx tubal occlusion, considered to be higher than HSG Simplest maneuver = repeat HSG in 1 month Study: 40pts with prox tubal occlusion  repeat HSG 1 month 60% patency office HSC: can’t visualize the proximal tube 3D U/S only useful if suspect fibroids, not specific for tubal patency

14. For each of the following clinical scenarios, match the appropriate diagnostic tools (A-D) (A) hysterosalpingography (HSG) (B) sonohysterography (SIS) (C) hysteroscopy (D) transvaginal ultrasound (1) 32yo woman coming in 6mo after tubal ligation reversal (2) 30yo woman with continuous vaginal bleeding refractory to medical therapy for 4 months. Office pelvic exam normal. (3) 25yo woman with history of PID and infertility (4) 33yo woman with positive pregnancy test and pelvic pain

14. For each of the following clinical scenarios, match the appropriate diagnostic tools (A-D) (A) hysterosalpingography (HSG) (B) sonohysterography (SIS) (C) hysteroscopy (D) transvaginal ultrasound A (1) 32yo woman coming in 6mo after tubal ligation reversal (2) 30yo woman with continuous vaginal bleeding refractory to medical therapy for 4 months. Office pelvic exam normal. (3) 25yo woman with history of PID and infertility (4) 33yo woman with positive pregnancy test and pelvic pain

14. For each of the following clinical scenarios, match the appropriate diagnostic tools (A-D) (A) hysterosalpingography (HSG) (B) sonohysterography (SIS) (C) hysteroscopy (D) transvaginal ultrasound A (1) 32yo woman coming in 6mo after tubal ligation reversal (2) 30yo woman with continuous vaginal bleeding refractory to medical therapy for 4 months. Office pelvic exam normal. (3) 25yo woman with history of PID and infertility (4) 33yo woman with positive pregnancy test and pelvic pain B

14. For each of the following clinical scenarios, match the appropriate diagnostic tools (A-D) (A) hysterosalpingography (HSG) (B) sonohysterography (SIS) (C) hysteroscopy (D) transvaginal ultrasound A (1) 32yo woman coming in 6mo after tubal ligation reversal (2) 30yo woman with continuous vaginal bleeding refractory to medical therapy for 4 months. Office pelvic exam normal. (3) 25yo woman with history of PID and infertility (4) 33yo woman with positive pregnancy test and pelvic pain B A

14. For each of the following clinical scenarios, match the appropriate diagnostic tools (A-D) (A) hysterosalpingography (HSG) (B) sonohysterography (SIS) (C) hysteroscopy (D) transvaginal ultrasound A (1) 32yo woman coming in 6mo after tubal ligation reversal (2) 30yo woman with continuous vaginal bleeding refractory to medical therapy for 4 months. Office pelvic exam normal. (3) 25yo woman with history of PID and infertility (4) 33yo woman with positive pregnancy test and pelvic pain B A D

15. For each of the following patients with infertility, select the most appropriate treatment option to help them achieve pregnancy (A) IVF with ICSI (B) Bilateral salpingectomy followed by IVF (C) IVF alone (D) Bilateral neosalpingostomy (E) Bilateral tubal reversal (1) 34yo woman with bilateral hydrosalpinges > 3cm confirmed on U/S. Husband has 44million sperm/mL on SA (2) 35yo woman with h/o severe dysmenorrhea, stage III endo. Husband has 66 million sperm/mL on SA. (3) 29yo woman with h/o chlamydial salpingitis, bilateral proximal tubal occlusion on HSG. Husband with 2 million sperm/mL (4) 27yo woman with Hulka clip BTL, newly married, wants 2 more children. Husband has 34 million sperm/mL on SA

15. For each of the following patients with infertility, select the most appropriate treatment option to help them achieve pregnancy (A) IVF with ICSI (B) Bilateral salpingectomy followed by IVF (C) IVF alone (D) Bilateral neosalpingostomy (E) Bilateral tubal reversal B (1) 34yo woman with bilateral hydrosalpinges > 3cm confirmed on U/S. Husband has 44million sperm/mL on SA (2) 35yo woman with h/o severe dysmenorrhea, stage III endo. Husband has 66 million sperm/mL on SA. (3) 29yo woman with h/o chlamydial salpingitis, bilateral proximal tubal occlusion on HSG. Husband with 2 million sperm/mL (4) 27yo woman with Hulka clip BTL, newly married, wants 2 more children. Husband has 34 million sperm/mL on SA

15. For each of the following patients with infertility, select the most appropriate treatment option to help them achieve pregnancy (A) IVF with ICSI (B) Bilateral salpingectomy followed by IVF (C) IVF alone (D) Bilateral neosalpingostomy (E) Bilateral tubal reversal B (1) 34yo woman with bilateral hydrosalpinges > 3cm confirmed on U/S. Husband has 44million sperm/mL on SA (2) 35yo woman with h/o severe dysmenorrhea, stage III endo. Husband has 66 million sperm/mL on SA. (3) 29yo woman with h/o chlamydial salpingitis, bilateral proximal tubal occlusion on HSG. Husband with 2 million sperm/mL (4) 27yo woman with Hulka clip BTL, newly married, wants 2 more children. Husband has 34 million sperm/mL on SA C

15. For each of the following patients with infertility, select the most appropriate treatment option to help them achieve pregnancy (A) IVF with ICSI (B) Bilateral salpingectomy followed by IVF (C) IVF alone (D) Bilateral neosalpingostomy (E) Bilateral tubal reversal B (1) 34yo woman with bilateral hydrosalpinges > 3cm confirmed on U/S. Husband has 44million sperm/mL on SA (2) 35yo woman with h/o severe dysmenorrhea, stage III endo. Husband has 66 million sperm/mL on SA. (3) 29yo woman with h/o chlamydial salpingitis, bilateral proximal tubal occlusion on HSG. Husband with 2 million sperm/mL (4) 27yo woman with Hulka clip BTL, newly married, wants 2 more children. Husband has 34 million sperm/mL on SA C A

15. For each of the following patients with infertility, select the most appropriate treatment option to help them achieve pregnancy (A) IVF with ICSI (B) Bilateral salpingectomy followed by IVF (C) IVF alone (D) Bilateral neosalpingostomy (E) Bilateral tubal reversal B (1) 34yo woman with bilateral hydrosalpinges > 3cm confirmed on U/S. Husband has 44million sperm/mL on SA (2) 35yo woman with h/o severe dysmenorrhea, stage III endo. Husband has 66 million sperm/mL on SA. (3) 29yo woman with h/o chlamydial salpingitis, bilateral proximal tubal occlusion on HSG. Husband with 2 million sperm/mL (4) 27yo woman with Hulka clip BTL, newly married, wants 2 more children. Husband has 34 million sperm/mL on SA C A E

IVF vs. surgery (Prolog p.189) Bilateral neosalpingostomy = attempt to repair/drain hydrosalpinges Often unsuccessful (closure/adhesions) ICSI: < 10 million / mL (Prolog) Tubal reversal after ring / hulka = most effective (83% pregnancy rate in one study). Don’t forget risk of ectopic approx 15%