Lecture 14: Conception, Fertility, Early Fetal Loss. provera. Depo-provera. Early Fetal Loss. Implanon. Norplant. Nuva Ring.

Transcription

1 Lecture 14: Conception, Fertility, Early Fetal Loss Birth Control (cont.) Conception What Influences Probability of Conception? Early Fetal Loss Infertility Fertility Enhancement Depo-provera provera Injectable contraceptive -- Progestin Shot every 3 months First year failure rate of 0.3% Can delay fertility for 6 months - 1 yr after discontinue Used by 30 million women Assisted reproduction Behavioral Biology of Women-2007 Norplant 6 sticks under skin Synthetic progestin Lasts up to 5 years First year failure rate of 0.05%, 3.7% over 5 years Inhibits ovulation, thickens and decreases cervical mucous, thins endometrial lining Progestin 4-5x 4 lower than birth control pills Used by 3 million women Implanon New birth control similar to Norplant but just 6 stick under skin Not yet readily available The Patch Works similar to the pill Contains progestin and estrogen Delivered through skin Put a new patch on once a week Reversible Nuva Ring Ring inserted in vagina Leave in for 3 weeks - take out for 1 Contains progestin and estrogen Works similar to the pill, but delivers hormones vaginally Should be more effective than bill < 1% failure rate Reversible 1

2 Homunculus in Sperm Conception The Ovum 2

3 The Ovum Shed into peritoneal cavity Rising estradiol causes fimbria to sweep ovum in to fallopian tube Cilia is activated in ampulla Ovum moves into fallopian tube and into ampulla Ovum continues to ripen in ampulla The Sperm 3

4 How do sperm get into Cervix? Opening of cervix has cilia to waft sperm through Components of seminal fluid - maybe prostaglandings - stimulate contractions in upper vagina to propel sperm into cervix 4

5 Capacitation The Sperm Change to hyperactivated motility pattern - whip-like beats of tail Change in surface membrane -- responsive to signals from oocyte Seminal fluid causes contractions of upper vagina Cervical mucous changes Cilia propel sperm into ampulla where fertilization takes place Chemicals surrounding egg may attract sperm In ampulla goes through capacitation 5

6 Fertilization 6

7 Acrosome Reaction Acrosome Reaction Binds to Oocyte Perivetelline Space Fusion with oocyte Zona pellucida hardens (Zona reaction) Final division of meiosis in oocyte 7

8 Male and Female Pronuclei form Polar Bodies Pronuclei of Male and Female Fuse 8

9 Fertilization Progesterone from granulosa cells causes enzymes in acrosome to leak out and dissolve matrix around egg One Sperm binds to zona pellucida Acrosome reaction Microvilli of egg engulf sperm Egg enzymes harden zona pellucida Final division of oocyte occurs Implantation YOU - Day 1! 8 Cell Stage Morula 9

10 100 Cell Stage Blastocyte Inner Cell Mass Trophoblast Day 5: Hatching from Zona Pellucida Day 8-10: Implantation Day 11 10

11 Implantation Implantation First forms a morula after initial cell division At 8-cell stage differentiates tissues Forms blastocyte Trophoplast Inner Cell Mass Trophoblast hatches out of zona pellucida for implantation How does the Embryo signal it s presence to the mother HCG (Human Chorionic Gonadotropin) Rescue Embryo produces HCG to signal the mother Mimics LH Maintains the corpus luteum What Influences the Probability of Conception? (Lipson & Ellison, 1996) 11

12 Behavior and Conception (Lipson & Ellison, 1996) Causes of Subfertility England Infertility: Caffeine Frequency (%) Endometriosis Tubal Damage Ovulatory Sperm Defects Unexplained Problems Caffeine Infertility Miscarriage birth defects lower birth weight earlier births Johnson & Everitt 2000 Alcohol Infertility Miscarriage birth defects lower birth weight earlier births Infertility: Alcohol Fecundability Ratio Alcohol and Conception No Alcohol 1-5 Drinks/week >10 Drinks/week (Jensen, et al., 1998) 12

13 Alcohol and Caffeine Consumption Alcohol and Caffeine Consumption Pregnancies/100 Cycles No Alcohol + < 1 cup coffee/day Alcohol + >1 cup coffee/day (Hakim et al., 1998) >50% reduction in probability of conception during a menstrual cycle where alcohol was consumed Caffeine enhanced negative effect of alcohol (no independent effect) Pregnancies/100 Cycles No Alcohol + < 1 cup coffee/day Alcohol + >1 cup coffee/day (Hakim et al., 1998) Infertility: Smoking Smoking and Conception Smoking Infertility lower birth weight Fecundability Ratio Nonsmokers Female Smokers Male Smokers (Curtis et al., 1997) Nonsmokers had a dose response relationship with caffeine No dose- response with caffeine in smokers Smoking and Caffeine Consumption Fecundability Ratio Nonsmoker < 300 mg/d Nonsmokers mg/d Nonsmokers > 700 mg/d Smokers with >300 mg/d Sperm counts decrease during IVF treatment Male Infertility Caffeine Consumption (Jensen et al., 1998) 13

14 Timing of Intercourse? Timing of Intercourse and Conception Lovers by Paolo Fiammingo Dunson et al., 1999 Early Fetal Loss HCG Concentrations in 5 women with early Pregnancy Loss (Wilcox et et al., al. 1988) Wilcox Study 25% chance of conceiving with each cycle 31% pregnancies ended in miscarriage Doesn t t include loss before HCG secretion detected or if HCG too low Risk didn t t increase if had just 1 miscarriage No increased loss if conceived in next cycle after miscarriage Higher rate of miscarriage in women who eventually conceived Wilcox et al Early Fetal loss in Bangladesh 14

15 Holman Study Observed early pregnancy loss was 34% No difference between this and the western sample Holman Study Observed early pregnancy loss was 34% Extend findings back to period between conception and HCG detection 18-year year-olds - 64% loss 28-year year-olds - 85% loss 38-year year-olds - 96% loss 48-year year-olds - 99% loss Criticisms: Problems with mathematical model Fecundability must be almost 100% for this rate of loss Age and Conception Chromosomal Abnormalities & Age Fecundity decreases with age Increased chromosomal abnormalities 15

16 Age and Down s s Syndrome Risk Percent Risk Age Conception and Age Increased chromosomal abnormalities Zona pellucida too dense -- no implantation (Scher and Dix, 1990) Traditional Methods - Fertility Enhancement Oral Consumption Consumption of Dill Wild Rue Wormwood Rome, 1st Century 11 century Middle East 11 century Middle East "Hot" Foods (fish, eggs, brown sugar Modern Afghanistan almonds, dates, ginger, garlic, raisins) Ginger Intravaginal Alum Linseed Oil Frankincense & Wormwood Mechanical Application of vacuumed containers Wearing of fresh skins Massage to move navel Magico-Religious Jivaro of Peru Greco-Roman Greco-Roman 13th century Middle East Greco-Roman, modern Afghanistan Central Asia Afghanistan Clomid Perganol in vitro Fertilization Intra-Uterine Insemination Sex Selection GIFT ZIFT Assisted Reproduction 16

17 Fertility Drug: Clomid Fertility drug given to women to promote ovulation Ring structure similar to estradiol Binds to receptors for estrogen Hypothalamus thinks estrogen is low and pumps out FSH to make more estrogen So causes woman to produce estrogen on her own Multiple births Possibly associated with ovarian cancer (concern for women who donate eggs) Fertility Drug: Perganol (Human Menopausal Gonadotropin) LH and FSH combined (distilled from menopausal urine) Stimulates follicular growth and estrogen production Mid-cycle dose of HCG to stimulate ovulation (mimicking action of LH) Multiple gestation risk (higher than clomid) Fertility Treatment: in vitro Fertilization (IVF) Take fertility drugs to get several eggs to mature Ultrasound to watch follicular development When follicle mature get dose of HCG (as an LH mimic - to encourage follicular development) After 36 hours (just before ovulation would occur naturally) surgically remove eggs Fertilization outside (in petri dish) of body Grow cells Put back in hopes 1 will implant Tubal blockage, as a result of infection Low sperm count (select best sperm) Fertility Treatment: Intra-Uterine Insemination (IUI) Take fertility drugs to get several eggs to mature Ultrasound to watch follicular development When follicle mature get dose of HCG (high enough to cause ovulation Inseminate with partner s s sperm in the uterus GIFT ZIFT Gamete Intrafallopian Transfer Mix egg and sperm and put back in fallopian tube before fertilization Zygote Intrafallopian Transfer Put zygote in fallopian tube (instead of uterus) 17

18 Y-sperm lighter can separate out Centrifuge Avoid sex-linked recessive diseases Sex Selection Assisted Reproduction Implications Higher rate of multiple births Assisted Reproduction Implications Percentage with Low Birth Weight Higher rate of multiple births Lower birth weight of singletons AND multiples General Population Singletons Assisted Reproduction Singletons Schieve et al., 2002 Percent Risk of Low Birth Weight & Procedure Type Fresh Embryo, nondonor oocyte 10.5 Frozen Embryo, nondonor oocyte 14 Fresh embryo, donor oocyte 11.8 Frozen Embryo, Donor Oocyte 8.7 Gestational Carrier 6.6 No Assistance Schieve et al., 2002 Possible Causes of Low Birth Weight with Assisted Reproduction Human Menopausal gonadotropin (Perganol) increases insulin-like like growth factor-binding protein - intrauterine growth restricts Increased rates of structural abnormalities of the placenta Pregnancy-induced hypertension Increased levels of endometrial proteins Elective cesarean section - earlier delivery Schieve et al.,

19 Assisted Reproduction Implications Assisted Reproduction Implications Higher rate of multiple births Lower birth weight of singleton AND multiples Greater risk of short and long term disabilities and death with low birth weight Higher rate of multiple births Lower birth weight of singletons AND multiples Greater risk of short and long term disabilities and death with low birth weight Higher rates of birth defects Assisted Reproduction & Birth Defects 10% 9% 8% 7% 6% 5% 4% 3% 2% 1% 0% 4.20% Natural Conception 9.70% 9.50% Intracytoplasmic Sperm Injection In Vitro Fertilization Assisted Reproduction & Birth Defects Singleton Births 4% 4% 3% 3% 2% 2% 1% 1% 0% 1.6% 1.3% 0.6% 2.7%2.7% 1.3% 2.7% 3.8% 1.1% Cardiovascular Urogenital Musculoskeltal Intracytoplasmic Sperm Injection In Vitro Fertilization Natural Hansen et al., 2002 Hansen et al., 2002 Possible Causes of Increased Birth Defects with Assisted Reproduction Underlying cause of their infertility Medications to induce ovulation Medications to maintain pregnancy early on Freezing and thawing of embryos Potential for polyspermic fertilization Delayed fertilization of oocyte Hansen et al., 2002 Assisted Reproduction 23% success rate 2.6 times risk of low birth weight Twice the risk of major birth defects Mitchell

20 Assisted Reproduction 23% success rate 2.6 times risk of low birth weight Twice the risk of major birth defects However 94% will be of normal birth weight 91% free of major birth defects Mitchell 2002 Views of Pregnancy Next Time Gestational Development The Physiology of Pregnancy Pica eating Pregnancy Sickness Energetics of Pregnancy 20