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 Couple’s failure to achieve

pregnancy after one year of regular, unprotected intercourse

US ~ 15% couples Incidence has remained stable over

last three decadesPrimary Infertility ??

Secondary Infertility ??

Average Conception Rates% of Couples Length of time

20% Conceive within 1 month60% Conceive within 6 months75% Conceive within 9 months80% Conceive within 12 months90% Conceive within 18 months

Causes of Infertility Multiple factors 20%

Male factors 40% Female factors 40%

Ovulatory factor 15-20%Peritoneal factor 40%

Uterine-tubal factor 30%Cervical factor 5-10%

Unexplained infertility 20%

Aging and female infertility As age increases follicular phase

becomes shorter and estradiol begins to rise earlier

Increased rate of follicular atresia after 37-38

Increased rate of spontaneous miscarriage

Aging and female infertilityAge Pregnancy

(1yr)Miscarriage

Rate20-25 90 9.7%26-30 85 10%31-35 75 11.5%36-40 65 21.4%>40 50 42.2%

What’s age got to do with it?

Intercourse on most fertile day

50% achieve pregnancy age 19-2640% achieve pregnancy age 27-3430% achieve pregnancy age 35-39

So what’s so hard??

Parts is Parts Adequate numbers of healthy sperm (male factor)

Mature ovum released in predictable fashion (ovarian factor)

Cervix must capture, nuture and release sperm into uterus and tubes (cervical factor)

Fallopian tubes must have a functional anatomic relationship to facilitate ovum capture (peritoneal

factor) Fallopian tube must be patent and capable of

transfer (tubal factor) Uterus must be receptive to implantation and

supporting pregnancy (uterine factor)

Male Factor Evaluation Physical exam

Environmental/occupational exposures Semen analysis

> 20 millionMotility > 50%Volume > 2mL

Morphology > 30% normal 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

Hypothalamic-pituitary dysfunction Intracranial tumors

PCOS Ovarian abnormalities

Thyroid disease 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

Basal body temperature Serum progesterone (mid-luteal Day19-22)

12 - 15 ng/mL considered evidence of ovulation Ovulation predictor kits (LH surge)

Ultrasound

Basal Body Temperature Temperature first thing in the morning

Biphasic pattern suggestive of ovulation Common to have dip the day of ovulation Temperatures rise after ovulation due to

progesterone from corpus luteum If temperatures drop late in the luteal phase don’t waste money on a pregnancy

test!

Female Factor Infertility - Uterine & Tubal Factors

Fibroids Intrauterine adhesions (Asherman’s)

Congenital malformations Tubal occlusion (PID most common)

Endometrial abnormalities

Tubal Adhesions

Mullerian Anomalies

Anomaly Frequency Bicornuate uterus (37 percent)

Arcuate uterus (15 percent) Incomplete septum (13 percent)

Uterus didelphys (11 percent) Complete septum (9 percent) and

Unicornuate uterus (4.4 percent)

Hysterosalpingogram Radiopaque dye through the cervix under x-ray watching dye fill uterus and

spill from tubes into peritoneal cavity

Ultrasonography Non-invasive

3D contours of uterus and endometrium as well as ovaries

MRI More distinct delineation of soft

tissue structures 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.

Structural abnormalities Abnormal mucous production

Female Factor Infertility - Cervical Factors

Evaluation should include post-coital test

Treatment includes intrauterine insemination

Smoking and Female Fertility Interferes with gametogenesis,

fertilization & implantation Reduces estrogen levels

Nicotine alters FSH/LH release decreasing LH surge

Nicotine stimulates cortisol secretion Earlier menopause by 2-3 years

Fertility rates lower (30%)

Smoking and Male Fertility Impaired sperm concentration,

motility & morphology Decreased libido

Combined with caffeine consumption increases number of non-viable

sperm

Assisted Reproduction

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

IVF Ovarian stimulation with gonadotropins

Oocyte retrieval (36 hours after hCG) Oocyte culture - sperm added after 4-6

hours (50,000 per oocyte) 65-80% of mature oocytes will fertilize

Examined at the pro-nuclear stage Cryopreservation of unused embryos (two

thirds will survive freezing/thawing)

IVF Embryo transfer 8-10 cell stage (72-

80 hours after retrieval) Multiple pregnancy rate 35%

Rise in hCG indicates pregnancy while drops indicate a failed cycle