Neil Goodman, MD, FACE

Transcription

1 Initial Workup of Infertile Couple: Female Neil Goodman, MD, FACE Professor of Medicine Voluntary Faculty University of Miami Miller School of Medicine

2 Scope of Infertility in the United States Affects 2-4 million couples Relative factors: Delayed childbearing Sexually transmitted diseases Advanced reproductive technologies Absolute infertility (sterility) Absence of sperm (azoospermia) Absence of oocytes (premature ovarian failure) Absence of functional tubes Subfertility or relative infertility: reduced fertility potential

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7 Ovarian Reserve

8 Age-Dependent Follicle Pool Initial pool of primordial follicles at 16 to 20 weeks of fetal life is believed to encompass approximately 6 to 7 million oocytes. At birth ovaries contain 7 million oocytes By menarche, about 300,000 remain. Only about 450 mono-follicular ovulations occur during a reproductive life of approximately 30 years. First consideration in treating a woman for infertility is always age

9 Age-Specific Fertility

10 Reproductive Aging Number of oocytes decreases with age, independent of ovulation or OCP use Quality of oocytes decreases with advancing age Increased mitotic spindle abnormalities Increased rates of single chromatid abnormalities Increased aneuploidy in preimplantation embryos At age 38 approximately 50% of oocytes are aneuploid

11 Fertility and Miscarriage Rates as a Function of Maternal Age

12 Diminished Ovarian Reserve Women of reproductive age having regular menses whose response to ovarian stimulation or fecundity is reduced compared with those women of comparable age. Women at risk over age 35 years family history of early menopause single ovary or history of previous ovarian surgery, chemotherapy, or pelvic radiation therapy unexplained infertility poor response to gonadotropin stimulation planning treatment with assisted reproductive technology (ART)

13 Pregnancy rate (%) Assessing Ovarian Reserve: CD 3 FSH/E2 High values (>10 20 IU/L) have been associated with both poor ovarian stimulation/failure to conceive basal serum FSH concentration is normal but the serum estradiol level is elevated (>60 80 pg/ml) in the early follicular phase, associeated with poor response to stimulation and poor pregnancy rate Total Delivery 5 0 < >25 Basal Day 3 FSH (miu/ml) Scott RT et al. Fert Steril :651-4

14 Assessing Ovarian Reserve: Antral Follicle Count Antral follicle count (AFC) is the sum of antral follicles in both ovaries, as observed with transvaginal ultrasonography duringthe early follicular phase. Antral follicles have been defined as measuring 2 10mmin mean diameter in the greatest twodimensional plane. A low AFC is considered to be 3 6 total antral follicles (mean of 5.2 with SD 2.11) and is associated with poor response to ovarian stimulation during IVF, but does not reliably predict failure to conceive

15 Antral Follicle Count Low AFC is considered to be 3 6 total antral follicles (mean of 5.2 with SD 2.11) Transvaginal Ultrasound of Ovary

16 Antimullerian Hormone Produced by follicular granulosa cells Determine success with various ART procedures Optimize ovarian stimulation protocol Does not fluctuate throughout a woman s menstrual cycle Ranges Consistent with PCOS:>= 4.0 Normal Ovarian Reserve: Poor Ovarian Response: Very Poor Ovarian Response: <0.2

17 Categories of Infertility Combined Unexplained 25% 10% 30% Female 35% Male

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19 Evaluation of Ovulation Oligomenorrhea and hyperandrogenism requires evaluation for PCOS Urinary home LH surge determination Cycle day 21 progesterone level Ultrasound observation of folliculogenesis Thyroid function tests and prolactin

20 OVULATION: FOLLICULOGENESIS

21 Single Follicle Development

22 POLYCYSTIC OVARY String of Pearls Sign

23 Luteal Phase Progesterone Pulsatile release, thus single level may not be useful unless elevated Performed 7 days after presumptive ovulation by LH surge testing Done properly, >3 ng/ml consistent with ovulation

24 Uterine Abnormalities Ultrasonography (US) and other imaging modalities such as three-dimensional (3- D) ultrasound and magnetic resonance imaging (MRI) may be used to diagnose uterine pathology leiomyomas congenital malformations ovarian pathology

25 Ultrasound Presentation of Normal Female Reproductive Anatomy

26 Hysterosalpingography Defines the size and shape of the uterine cavity and can reveal developmental anomalies unicornuate septate bicornuate uteri Acquired abnormalities endometrial polyps submucous myomas, synechiae HSG has relatively low sensitivity (50%) and positive predictive value (PPV; 30%) for diagnosis of endometrial polyps and submucous myomas HSG cannot reliably differentiate a septate from a bicornuate uterus,further evaluation with pelvic MRI or 3D ultrasonography

27 Hysterosalpingogram 1) Determine patency of the fallopian tubes 2) Detect uterine cavity abnormalities

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29 Hysterosalpingogram Bicornuate uterus Hydrosalpinx Submucosal fibroids

30 MRI Bicornuate Uterus

31 Saline Infusion Sonogram Endometrial Polyp

32 Ovulation Induction

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34 Fertilization

35 FECUNDIBILITY MONTH COUPLES REMAINING PERCENT PREGNANT % per month

36 OVULATION: FOLLICULOGENESIS

37 Treatment of Ovulation Disorders Oocyte maturation and ovulation is FSHdependent Clomiphene citrate stimulates pituitary release of FSH through hypothalamic interaction FSH can be given parenterally as gonadotropin therapy

38 Unexplained Infertility Absence of a defined cause of infertility after evaluating the four infertility factors Subfertile couples have some potential for conceiving More than 30% of couples with unexplained infertility will become pregnant within 3 years of expectant management If female partner >30 years old and infertility is long-standing, treatment is appropriate

39 Unexplained Infertility 1-2 years 2-3 years 3-5 years >5 years

40 Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility

41 Clomiphene Citrate First line treatment in PCOS/anovulation Limited success in unexplained infertility Avoid empirical trials 40% pregnancy rate 85% of pregnancies in three cycles of adequate response Minimal improvement in pregnancy rates with doses greater than 100mg x 5 days 50% of CC cycles with dysmucorrhea by PCT Letrozole 5mg x 5 days

42 Clomiphene Citrate: Insurance Treatment Insure: adequate follicle growth by US and E2 documentation Insure: HCG administering for oocyte maturation and release, and corpus luteum formation Insure: adequate sperm availability by IUI Insure: adequate uterine receptivity by administering transvaginal progesterone

43 Gonadotropin Therapy Recombinant FSH: Follistim/Gonal F Menotropins (purified urinary gonadotropins) Start CD3 PCOS/<35: 75 units AMA (>35): 150/300 US/E2 q2-3 days Step up/step down Control follicle growth to peak CD Lead follicle 16mm/ 1-3 E2 200pg/ml/per follicle total <2000 Micro HCG = LH

44 IVF

45 Assisted Reproductive Technologies Intrauterine insemination In vitro fertilization Intracytoplasmic sperm injection

46 Indications for IVF Absolute Tubal factor Severe oligoasthenospermia Relative (15-25% pregnancy rates per cycle of COH/IUI) Unexplained infertility Endometriosis Prior treatment failure (ovulation induction) (? Evaluate adequacy of treatment)

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48 A high quality day 3 human embryo at the 8-cell stage 6 cells are visible in this plane of focus

49 Intracytoplasmic Sperm Injection (ICSI)

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