The Challenge of the Miracle of Life - Infertility Jennifer McDonald DO

Fecundability Probability of achieving a pregnancy within one menstrual cycle 25% for normal couples

Infertility l Couple’s failure to achieve pregnancy after one year of regular, unprotected intercourse l US ~ 15% couples l Incidence has remained stable over last three decades Primary Infertility ?? Secondary Infertility ??

Average Conception Rates

Causes of Infertility l Multiple factors 20% l Male factors 40% l Female factors 40% Ovulatory factor 15-20% Peritoneal factor 40% Uterine-tubal factor 30% Cervical factor 5-10% l Unexplained infertility 20%

Aging and female infertility l As age increases follicular phase becomes shorter and estradiol begins to rise earlier l Increased rate of follicular atresia after l Increased rate of spontaneous miscarriage

Aging and female infertility

What’s age got to do with it? Intercourse on most fertile day 50% achieve pregnancy age % achieve pregnancy age % achieve pregnancy age 35-39

So what’s so hard??

Parts is Parts l Adequate numbers of healthy sperm (male factor) l Mature ovum released in predictable fashion (ovarian factor) l Cervix must capture, nuture and release sperm into uterus and tubes (cervical factor) l Fallopian tubes must have a functional anatomic relationship to facilitate ovum capture (peritoneal factor) l Fallopian tube must be patent and capable of transfer (tubal factor) l Uterus must be receptive to implantation and supporting pregnancy (uterine factor)

Male Factor Evaluation l Physical exam l Environmental/occupational exposures l Semen analysis > 20 million Motility > 50% Volume > 2mL Morphology > 30% normal l Endocrine evaluation if warranted

Female Factor Infertility - Peritoneal Factors Endometriosis Pelvic Adhesions Pregnancy rates after treatment as high as 75% for mild disease and as low as 30% for severe disease Diagnosis = Laparoscopy

l Hypothalamic-pituitary dysfunction l Intracranial tumors l PCOS l Ovarian abnormalities l Thyroid disease l Androgen excess Female Factor Infertility - Ovulatory Factors Ovulation restored in 90% of cases due to endocrine factors. Other cases rely on ovulation induction with medications

Evidence of Ovulation l Basal body temperature l Serum progesterone (mid-luteal Day19-22) l ng/mL considered evidence of ovulation l Ovulation predictor kits (LH surge) l Ultrasound

Basal Body Temperature l Temperature first thing in the morning l Biphasic pattern suggestive of ovulation l Common to have dip the day of ovulation l Temperatures rise after ovulation due to progesterone from corpus luteum l If temperatures drop late in the luteal phase don’t waste money on a pregnancy test!

Female Factor Infertility - Uterine & Tubal Factors l Fibroids l Intrauterine adhesions (Asherman’s) l Congenital malformations l Tubal occlusion (PID most common) l Endometrial abnormalities

Tubal Adhesions

Mullerian Anomalies

Anomaly Frequency l Bicornuate uterus (37 percent) l Arcuate uterus (15 percent) l Incomplete septum (13 percent) l Uterus didelphys (11 percent) l Complete septum (9 percent) and l Unicornuate uterus (4.4 percent)

Hysterosalpingogram l Radiopaque dye through the cervix under x-ray watching dye fill uterus and spill from tubes into peritoneal cavity

Ultrasonography l Non-invasive l 3D contours of uterus and endometrium as well as ovaries

MRI l More distinct delineation of soft tissue structures l MR imaging has been shown to be both sensitive and specific and is clearly less invasive than laparoscopy, which was considered the gold standard for diagnosis of anomalies.

l Structural abnormalities l Abnormal mucous production Female Factor Infertility - Cervical Factors Evaluation should include post-coital test Treatment includes intrauterine insemination

Smoking and Female Fertility l Interferes with gametogenesis, fertilization & implantation l Reduces estrogen levels l Nicotine alters FSH/LH release decreasing LH surge l Nicotine stimulates cortisol secretion l Earlier menopause by 2-3 years l Fertility rates lower (30%)

Smoking and Male Fertility l Impaired sperm concentration, motility & morphology l Decreased libido l Combined with caffeine consumption increases number of non-viable sperm

Assisted Reproduction l IVF (in vitro fertilization) l GIFT (gamate intra-fallopian transfer) l ZIFT (zygote intra-fallopian transfer)

IVF l Ovarian stimulation with gonadotropins l Oocyte retrieval (36 hours after hCG) l Oocyte culture - sperm added after 4-6 hours (50,000 per oocyte) l 65-80% of mature oocytes will fertilize l Examined at the pro-nuclear stage l Cryopreservation of unused embryos (two thirds will survive freezing/thawing)

IVF l Embryo transfer 8-10 cell stage (72-80 hours after retrieval) l Multiple pregnancy rate 35% l Rise in hCG indicates pregnancy while drops indicate a failed cycle