Conception

Conception: Transition to Pregnancy

Pregnancy

humans are best able to conceive while in their late teens and twenties; infertility increases with age

pregnancy period usually 40 wks. ± 2 wks

dated from last mentratration, so actual length of pregnancy is usually two weeks less

remember that length of follicular phase can be variable, while length of luteal phase is constant (14 days)

estimated date of confinement (EDC) = due date

Male Factors Contributing to Pregnancy

(1) Ejaculate

volume 1.5 - 5 cc; concentration is > 20 X 10⁶sperm per cc, so total > 60 X 10⁶

motility: > 40 % need to be motile

forms gel immediately after release, liquifies within 20-30 minutes; alkaline pH protects against acidity of vagina

of estimated 200 million sperm ejaculated, less that 200 reach area of ovum

(2) Entry into female genital tract: rapid; sperm found in fallopian tube 5 minutes after insemination

cilia and muscular contractions of uterus and fallopian tubes transport sperm; female orgasm not required
sperm motility maintained up to 7 days in cervical mucus; gradual transport from endocervical crypts ensure that conception can take place several days after intercourse

(3) Capacitation: process of sperm becoming competent to cause fertilization

does not require female genital tract; can be induced by removing seminal plasma antigens from membrane
sperm retain fertilization capability for 48 hours

(4) Acrosome Reaction: sperm contact with follicular antigens causes merging and breakdown of plasma and acrosomal membranes Þ release of lytic acrosomal enzymes thought to be involved in sperm penetration of cumulus oophorus

Tests:

ultracritical assessment: careful studying of the morphology of sperm – can predict the fertility of a man
antisperm Ab – often present after vasectomy; can cause infertility even after the vasectomy is reversed
acrosome reaction test

Female Factors Contributing to Pregnancy

(1) Vagina – hostile to sperm

sperm readily enter ovulatory mucus; cervical mucus guides, protects and nourishes sperm

ovulatory mucus: stretches, alkaline, abundant and demonstrates ferning under microscopic exam

follicle arrested in prophase I Þ resumes meiosis when released, stops at metaphase II Þ completes when fertilized

(2) Ovum Capture and Transport –hormonal changes in late follicular, periovulatory, and early luteal phases are all probably critical to the function of the fallopian tubes

fimbria brought in contact with ovary (due to contraction of the fimbria ovarica, mesosalpinx, and utero-ovarian ligament)

sticky cumulus mass attaches to adhesive sites on the cilia of the fimbria

ciliary beat of fimbria and muscular contractions of fallopian tubes transport cumulus-egg mass

cumulus-egg mass reaches isthmic-ampullary junction in about 30 hrs; remains there another 30 hrs (tubal lock); is then rapidly transported through the isthmus to the uterus by about 72 hours after its original release

tubal lock is probably initiated by Ý estradiol; Ý progesterone probably causes the egg to resume movement

fertilizable lifespan of the human ovum is estimated to be 12-24 hours

(3) Fertilization – usually occurs in ampulla of the fallopian tube; successful fertilization requires three steps:

(1) Penetration of cumulus mass

(2) Binding to and penetration of zona pellucida; receptors are species specific

hard "impenetrable" zona syndrome is a source of female reproductive failure – release of cortical granules from periphery of the ovum usually prevents other sperm from fertilizing the egg

(3) Fusion of sperm and egg membranes and formation of pronuclei – leads to protrusion of second polar body

area of male reproductive failure Þ hamster egg penetration test used to detect it

(4) Embryo Development Transport and Implantation

embryo has divided to the morula stage by the time it reaches the uterus Þ 72 hours post ovulation

blastocyst hatches from zona pellucida and attaches to decidualized endometrium (implantation)Þ 6 days postovulation

implantation begins with membrane approximation and is followed by formation of junctional complexes; trophoblast cells invade endometrial cells and begins formation of the decidua; probably involves signals from the embryo

Abnormal Development

10-15% don’t divide, 15-20% don’t implant;15-27% abort during 2^nd post ovulatory wk

1^st trimester losses are difficult to prevent Þ developmental errors usually occur long before the problem manifests

miscarriage = spontaneous abortion; risk Ý with maternal age

habitual abortion = 3 consecutive early pregnancy losses; chance of next pregnancy being successful only 50%

causes: luteal phase defect, balanced translocation, autoimmune diseases, structure abnormalities, idiopathic

ectopic pregnancy: 1% of pregnancies; sites include fallopian tube, ovary, bowel, peritoneum and liver

risk factors: infertility, tubal damage, pelvic inflammatory disease, IUD use

complications: loss of tubal function, hemorrhage, death

treatment: methotrexate Þ inhibits tetrahydrofolic acid synthesis; embryo is dependent on folic acid

surgery Þ if embryo is large, tube must be removed; if small, tube can be sparedÞ 20% chance of recurrence

diagnosis – human chorionic gonadotropin (HCG) should double every 2 to 3 days during 1^st trimester; if HCG levels do not rise it suggests an ectopic pregnancy