HUMAN REPRODUCTION BIOLOGY 269

1. HUMAN REPRODUCTIONBIOLOGY 269

2. So far, we have discussed sexual anatomy and physiology, sexual response, and fertilization with the assumption that pregnancy is desired. That is often not the case – many forms of contraception are now available. These can be grouped as: Natural methods Barriers Spermicides Intrauterine devices Oral contraceptives Implanted progestins Sterilization 1800-1900: Average family size in US dropped from 7 to 3.5 children 1933: Average family had 2.3 children 1957: Average family had 3.7 children Since 1972: Average family has ~2 children

3. Natural Methods: 1. Rhythm: Sperm viability: few days Oocyte viability: one day Avoid sexual intercourse 5-7 days on either side of expected ovulation Length of cycle / time of ovulation vary: unsafe period Thus: rhythm method generally recommended only when: a) The woman b) The couple c) The couple

4. Natural Methods: 2. Basal Temperature Monitoring: Few hours before ovulation: body temperature drops fraction of degree Few hours after ovulation: body temperature rises fraction of degree Use temperature changes to detect ovulation, avoid intercourse Basal temperature monitoring generally recommended only when: a) The woman b) The couple c) The couple d) The couple

5. Natural Methods: 3. Cervical Mucous Screening: Most of cycle: cervical mucous thick, stringy Near time of ovulation: cervical mucous thins Threads of mucous stretched to detect “stringiness”, avoid intercourse near ovulation Cervical mucous screening generally recommended only when: a) The woman b) The couple c) The couple d) The couple is willing and able to accept a relatively high risk of pregnancy

6. Natural Methods: 4. Withdrawal or Coitus Interruptus: Penis must be completely withdrawn from vagina before ejaculation Recommendations similar to other natural methods: a) The woman has a very regular menstrual cycle b) The couple c) The couple is willing and able to accept a relatively high risk of pregnancy

7. Most failures due to improper use Failure rates: Number of pregnancies per 100 “woman years” = 5 women for 20 years; 10 women for 10 years; 50 women for 2 years; etc No method: 25 – 35 year old woman . . . . . . . . . . . . . . . . . 80 - 90 No method: > 35 year old woman . . . . . . . . . . . . . . . . . 45 - 60 Rhythm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 - 35 Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 30 Spermicide alone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 25 Condom, diaphragm, cervical cap . . . . . . . . . . . . . . . . . . . . 5 - 12 Barrier plus spermicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 - 5 Intrauterine devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3 - 3 Oral/Inserted/Patch contraceptives . . . . . . . . . . . . . . . . . . . 0.1 - 3 Implanted/injected hormones . . . . . . . . . . . . . . . . . . . . . . . . 0.1 - 1 Female sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.5 Male sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.2

8. Spermicides: Creams, jellies, sponges, foams, dissolving films, etc. Can be applied 30 – 60 minutes before intercourse May be used with or without barriers Must be reapplied before each sexual intercourse Usually no effect on sexual motivation or sexual response Spermicides widely recommended for most couples who Some individuals have

9. Most failures due to improper use Failure rates: Number of pregnancies per 100 “woman years” = 5 women for 20 years; 10 women for 10 years; 50 women for 2 years; etc No method: 25 – 35 year old woman . . . . . . . . . . . . . . . . . 80 - 90 No method: > 35 year old woman . . . . . . . . . . . . . . . . . 45 - 60 Rhythm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 - 35 Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 30 Spermicide alone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 25 Condom, diaphragm, cervical cap . . . . . . . . . . . . . . . . . . . . 5 - 12 Barrier plus spermicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 - 5 Intrauterine devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3 - 3 Oral/Inserted/Patch contraceptives .. . . . . . . . . . . . . . . . . . . 0.1 - 3 Implanted/injected hormones . . . . . . . . . . . . . . . . . . . . . . . . 0.1 - 1 Female sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.5 Male sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.2

10. Barrier Methods: 1. Condom: Must be put on and removed while penis erect Must be put one before emission phase of ejaculation Some effect possible on sexual motivation or sexual response Can be used with or without spermicides; more effective if both used Also protects against sexually transmitted diseases Widely recommended for.

11. Barrier Methods: 2. Diaphragm or Cervical Cap: Fits tightly in vagina, just below cervix May be used with or without spermicide; more effective if both used Risk of displacement during foreplay / intercourse Usually no effect on sexual motivation or sexual response Must remain in place until no living sperm in vagina: hours Generally recommended Requires fitting & prescription.

12. Barrier And Spermicide: Vaginal Sponge: Fits tightly in vagina next to cervix Both barrier (absorbs sperm) and spermacide Can be used for multiple times of intercourse up to 24 hours Must remain in place until no living sperm are present in vagina: hours Usually no effect on sexual motivation or response Generally recommended for couples who are motivated enough to use it regularly and correctly. Does not require prescription.

13. Most failures due to improper use Failure rates: Number of pregnancies per 100 “woman years” = 5 women for 20 years; 10 women for 10 years; 50 women for 2 years; etc No method: 25 – 35 year old woman . . . . . . . . . . . . . . . . . 80 - 90 No method: > 35 year old woman . . . . . . . . . . . . . . . . . 45 - 60 Rhythm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 - 35 Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 30 Spermicide alone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 25 Condom, diaphragm, cervical cap . . . . . . . . . . . . . . . . . . . . 5 - 12 Barrier plus spermicide . . . . . . . . . . . . . . . . . . . . . .. . . . . . . 1 - 5 Intrauterine devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3 - 3 Oral/Inserted/Patch contraceptives . . . . . . . . . . . .. . . . . . . . 0.1 - 3 Implanted/injected hormones . . . . . . . . . . . . . . . . . . . . . . . . 0.1 - 1 Female sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.5 Male sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.2

14. Intrauterine Devices: Inserted through cervix into uterus; left in place for months Produces mild inflammation of endometrium, inhibiting transport of sperm and /or implantation Usually no effect on sexual motivation or sexual response Two types in use: wrapped around plastic stem (“ParaGard”) (same activity as natural progesterone) embedded in plastic & slowly released (“Mirena”) May be Risk of Increased risk of Typically increases Thus: typically recommended

15. Most failures due to improper use Failure rates: Number of pregnancies per 100 “woman years” = 5 women for 20 years; 10 women for 10 years; 50 women for 2 years; etc No method: 25 – 35 year old woman . . . . . . . . . . . . . . . . . 80 - 90 No method: > 35 year old woman . . . . . . . . . . . . . . . . . 45 - 60 Rhythm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 - 35 Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 30 Spermicide alone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 25 Condom, diaphragm, cervical cap . . . . . . . . . . . . . . . . . . . . 5 - 12 Barrier plus spermicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 - 5 Intrauterine devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3 - 3 Oral/Inserted/Patch contraceptives . . . . . . .. . . . . . . . . . . . . 0.1 - 3 Implanted/injected hormones . . . . . . . . . . . . . . . . . . . . . . . . 0.1 - 1 Female sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.5 Male sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.2

16. A number of contraceptives deliver low amounts of estrogens and/or progesterone (either the natural hormone or synthetic forms) into the body over a prolonged period of time. These have a “negative feedback” on the pituitary gland, preventing it from releasing follicle stimulating hormone to start another follicle developing. This, of course, is just mimicing what happens normally just before and after ovulation and during pregnancy. - O - V - T - I - I

17. Oral contraceptives Progesterone alone or combinations of estrogen and progesterone, usually taken daily a) Negative feedback: Inhibits pituitary from producing follicle stimulating hormone and luteinizing hormone; no follicle development or oogenesis. b) Keeps mucous of cervix thick, preventing sperm penetration. c) Decreased growth of endometrium; embryo less likely to implant if fertilization does occur.

18. Oral contraceptives T : Alesse, Brevicon, Demulen, Desogen, Janest Levlen, Loestrin, Mircette, Necon, Norinyl, Ortho-Cept, Ortho-Cyclin, Ortho-Novum, TriCylcin, TriLevien, TriNorinyl, TriPhasil, Yasmin, Yaz E : Lybrel, Seasonale, Seasonique.

19. Oral contraceptives Progesterone alone or combinations of estrogen and progesterone, usually taken daily a) Negative feedback: b) Keeps mucous of cervix c) Decreased growth Increased risk of blood clots Some women: Less discomfort during menstruation Decreased acne Usually no effect on sexual motivation or sexual response

20. Vaginal hormonal contraceptives: Combinations of estrogen and progesterone, inserted into the vagina (typically once per month) Removed for menstruation a) Negative feedback: Inhibits pituitary from producing follicle stimulating hormone and luteinizing hormone; no follicle development or oogenesis. b) Keeps mucous of cervix thick, preventing sperm penetration. c) Decreased growth of endometrium; embryo less likely to implant if fertilization does occur. Increased risk of blood clots Some women: nausea, vomiting, vaginal bleeding, breast tenderness Less discomfort during menstruation Decreased acne Usually no effect on sexual motivation or sexual response

21. Transdermal hormonal contraceptives Combinations of estrogen and progesterone, absorbed through the skin from a patch a) Negative feedback: Inhibits pituitary from producing follicle stimulating hormone and luteinizing hormone; no follicle development or oogenesis. b) Keeps mucous of cervix thick, preventing sperm penetration. c) Decreased growth of endometrium; embryo less likely to implant if fertilization does occur. Increased risk of blood clots Some women: nausea, vomiting, vaginal bleeding, breast tenderness Less discomfort during menstruation Decreased acne Usually no effect on sexual motivation or sexual response

22. Most failures due to improper use Failure rates: Number of pregnancies per 100 “woman years” = 5 women for 20 years; 10 women for 10 years; 50 women for 2 years; etc No method: 25 – 35 year old woman . . . . . . . . . . . . . . . . . 80 - 90 No method: > 35 year old woman . . . . . . . . . . . . . . . . . 45 - 60 Rhythm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 - 35 Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 30 Spermicide alone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 25 Condom, diaphragm, cervical cap . . . . . . . . . . . . . . . . . . . . 5 - 12 Barrier plus spermicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 - 5 Intrauterine devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3 - 3 Oral / Inserted / Patch contraceptives . . . . . . . . . . . . . . . . . 0.1 - 3 Implanted/injected hormones . . . . . . . . . . . . . . . . . . . . . . . . 0.1 - 1 Female sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.5 Male sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.2

23. Implanted or Injected Progestins: Progestins = Silicon tubes containing progestins implanted under skin (e.g. Norplant) or Progestins injected 2 - 4 times / year (e.g. DepoProvera) Hormone slowly released into blood Similar mechanism as oral contraceptives: a) Negative feedback: Inhibits pituitary from producing follicle stimulating hormone and luteinizing hormone so no follicle development / oogenesis b) Keeps mucous of cervix thick, preventing sperm penetration c) Decreased growth of endometrium; embryo less likely to implant Can last Easily removable So far: no serious side effects Usually no effect on sexual motivation or response

24. Most failures due to improper use Failure rates: Number of pregnancies per 100 “woman years” = 5 women for 20 years; 10 women for 10 years; 50 women for 2 years; etc No method: 25 – 35 year old woman . . . . . . . . . . . . . . . . . 80 - 90 No method: > 35 year old woman . . . . . . . . . . . . . . . . . 45 - 60 Rhythm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 - 35 Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 30 Spermicide alone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 25 Condom, diaphragm, cervical cap . . . . . . . . . . . . . . . . . . . . 5 - 12 Barrier plus spermicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 - 5 Intrauterine devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3 - 3 Oral/Inserted/Patch contraceptives . . . . . . . . .. . . . . . . . . . . 0.1 - 3 Implanted/injected hormones . . . . . . . . . . . . . . . . . . . . . . . . 0.1 - 1 Female sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.5 Male sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.2

25. Sterilization 1. Vasectomy: Incisions in scrotum, both spermatic cords exposed Vas deferens isolated, tied twice, section cut out between ties Permanent Usually no effect on sexual motivation or sexual response Semen ~ normal volume (prostate & seminal vesicles) Sperm trapped behind cut must be absorbed; immune reaction possible

26. Sterilization 2. Tubal Ligation: Incisions made in abdomen Laparoscope used to identify Fallopian tubes Fallopian tubes isolated, tied twice, section cut out between ties Permanent Usually no effect on sexual motivation or sexual response

27. Sterilization 3. Tubal Implants (“Essure”): Silicone tubes inserted through vagina and uterus Causes scarring of Fallopian tubes, blocking sperm Permanent Usually no effect on sexual motivation or sexual response

28. Sterilization 4. Hysterectomy: Complete removal of uterus Fallopian tubes and ovaries may or may not also be removed Also stops menstrual periods

29. Most failures due to improper use Failure rates: Number of pregnancies per 100 “woman years” = 5 women for 20 years; 10 women for 10 years; 50 women for 2 years; etc No method: 25 – 35 year old woman . . . . . . . . . . . . . . . . . 80 - 90 No method: > 35 year old woman . . . . . . . . . . . . . . . . . 45 - 60 Rhythm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 - 35 Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 30 Spermicide alone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 25 Condom, diaphragm, cervical cap . . . . . . . . . . . . . . . . . . . . 5 - 12 Barrier plus spermicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 - 5 Intrauterine devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3 - 3 Oral/Inserted/Patch contraceptives . . . . . . . . . . . . . . . . . . . . 0.1 - 3 Implanted/injected hormones . . . . . . . . . . . . . . . . . . . . . . . . 0.1 - 1 Female sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.5 Male sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.2

30. Postcoital contraceptives or “Morning after pills” 1. Progesterone or estrogen/progesterone combinations (“Next Choice”, “Plan B”) Essentially concentrated forms of oral contraceptives Taken Prevents Thickens Inhibits Inhibits All states require

31. “Morning after pills” or postcoital contraceptives 2. Mifepristone (RU486) and Ulipristal (Ella) Blocks action of Can be used many days (Ulipirstal) or many weeks (Mifipristone) after fertilization Causes death and loss of endometrium (menstruation) Side effects similar to spontaneous abortion (miscarriage): Cramping, abdominal pain, bleeding, fatigue Requires prescription Commonly used in other countries for many years.

32. Most failures due to improper use Failure rates: Number of pregnancies per 100 “woman years” = 5 women for 20 years; 10 women for 10 years; 50 women for 2 years; etc No method: 25 – 35 year old woman . . . . . . . . . . . . . . . . . 80 - 90 No method: > 35 year old woman . . . . . . . . . . . . . . . . . 45 - 60 Rhythm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 - 35 Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 30 Spermicide alone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 - 25 Condom, diaphragm, cervical cap . . . . . . . . . . . . . . . . . . . . 5 - 12 Barrier plus spermicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 - 5 Intrauterine devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3 - 3 Oral/Inserted/Patch contraceptives . . . . . . . . . . . . . . . . . . . . 0.1 - 3 Implanted/injected hormones . . . . . . . . . . . . . . . . . . . . . . . . 0.1 - 1 Female sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.5 Male sterilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 - 0.2 Postcoital contraceptives . . . . . . . . . . . . . . . . . . . . . . . . . . . . ??

33. Postcoital contraceptives:Reliable failure rates not well establishedUsed primarily as emergency contraceptives or informally Progesterone or estrogen/progesterone mixtures; Ulipristal: Failure rate ~ 2% per use = 24% annual failure rate if used each cycle Mifepristone: Failure rate ~ 5% per use = 60% annual failure rate if used each cycle Thus: Recommended only as a last resort when other methods of contraception may have failed (e.g. broken condom) or when unprotected sexual intercourse occurred. Known as “emergency contraceptives”.

34. Despite many different methods of easily available contraception: More than half of all pregnancies in U.S. are unintended More than 1,200,000 abortions / year (>20% of all pregnancies) x