Recent Advances in Fertility Regulation

1. Recent Advances in Fertility Regulation Professor PC Ho Department of O&G University of Hong Kong

2. Condom or sheath Especially useful when coitus occurs infrequently and at irregular intervals Some protection against venereal disease Coincident use of spermicides advisable

3. Intrauterine contraceptive device Two types: 1. Inert e.g. Lippes 2. Bioactive e.g. copper T or 7 or levonorgestrel IUCD; need renewal every 3-5 years

4. Advantages of IUD 1. Highly effective 2. Little motivation 3. Non-coitus-related 4. Local effect 5. 90% conceive within 1 year of removal

5. New copper IUCD Cu T 380 A Cu T 220 C Multiload 250 & 375 Nova T Prerferred over inert devices

6. Advantages of new copper IUCDs 1. Smaller and easier to insert 2. Less side effects 3. Lower pregnancy rate <1/HWY

7. Complications of IUCD 1. Expulsion 2. Bleeding 3. Pain 4. Perforation 5. Pelvic infection 6. Pregnancy

8. Bleeding Most common complication requiring removal; may present with: 1. Increased menstrual flow 2. Longer periods 3. Intermenstrual bleeding

9. Management of bleeding problems May improve after several cycles NSAID 3. Anti-fibrinolytic agents 4. Oral iron 5. Remove IUCD/Change to smaller or LNG-IUCD

10. IUCD & ectopic pregnancy 1. Does not increase overall risk of ectopic pregnancy 2. Protects against IU pregnancy better than ectopic 3. Increased ectopic to intrauterine pregnancy ratio

11. Pelvic Inflammatory Disease No significant increase in low risk women IUCD related PID rare beyond 20 days

12. Contraindications 1. Active or recent P.I.D. 2. Known or suspected pregnancy 3. Undiagnosed abnormal vaginal bleeding 4. Suspected/confirmed genital tract malignancy 5. Congenital uterine abnormality or fibroids that prevent proper placement

13. Levonorgestrel IUCD Contains levonorgestrel which is slowly released Highly effective – Pearl Index 0-0.2/HWY Ectopic preg rate – 0.02%/year

14. Levonorgestrel IUCD Reduces menstrual blood loss but there is a higher incidence of intermenstrual bleeding/spotting Amenorrhoea 16.1% Spotting 8.9% Meno/metrorrhagia 7.6% (Siven & Stern 1994)

15. Levonorgestrel IUCD Incidence of PID lower than Nova-T Removal rates at 5 years due to PID LNG 0.8/HWY Nova T 2.2/HWY (Andersson et al 1994)

16. Modern combined oral contraceptives combination of oestrogen and progestogen taken daily for 21 days followed by an interval of 7 days Oestrogen - Ethinyl oestradiol 20 to 30 ug per tablet Progestogens: levonorgestrel; gestodene; desogestrel Failure rate < 0.1/HWY

17. OC pills - Side Effects Nausea & vomiting dizziness & headache breast tenderness fluid retention and weight gain Intermenstrual spotting/bleeding may disappear after a few cycles

18. Major complications of OC Increased risk of thromboembolism, cardiovascular diseases (CVA and myocardial infarction) Slightly increased risk of breast cancer and liver tumours (controversial - cervical cancer) Jaundice and liver dysfunction

19. COC - Absolute Contraindications Pregnancy Smoking in women over 35 Past or present evidence of thromboembolic disorders Complicated valvular heart disease Focal migraine Liver tumours

20. COC - Absolute contraindications Acute liver disease or cirrhosis DM with vascular complications including hypertension Moderate or severe hypertension with BP > 160/100 mm Hg Hypertension with vascular disease

21. COC - Relative contraindications (Risks usually outweigh benefits) Mild hypertension 140-159/90-99 mm Hg History of hypertension when BP cannot be evaluated Chronic liver disease other than severe cirrhosis Symptomatic biliary tract disease Known hyperlipidaemia

22. Benefits of COC (I) Reduction in risk of ovarian cancer Reduction in risk of endometrial cancer Menstrual benefits : Reduction in amount of blood loss mid-cycle pain menstrual irregularity premenstrual tension and dysmenorrhoea

23. Benefits of COC (II) Reduction in PID Protects against benign breast tumour Possible benefits protection against ovarian cyst, uterine fibroids and osteoporosis Highly effective form of contraception and protects against ectopic pregnancy

24. Third generation progestogens Desogestrel Gestodene Norgestimate Better lipid profiles

25. Concerns on new progestogens Do they increase the risk of deep vein thrombosis? Results are controversial and some of the results are probably due to the bias in the studies On the whole low dose OC pills are very safe; even if there is an increase in risk with new progestogens, the risk is small

26. Commonly asked questions Are combined OC pills safe in women over the age of 35? Yes, if the woman is healthy and non-smoking Can OC pills be used in women with uterine fibroids? Yes. OC pills do not induce growth of fibroids and may decrease bleeding in these women (ACOG 2001)

27. Commonly asked questions Can OC pills be used in SLE? In general, progestin-only methods should be used. Combined OC pills may be considered if SLE is stable and inactive with no thrombosis, nephropathy or antiphospholipid antibodies (ACOG, 2001)

28. Commonly asked questions Can OC pills be used in women with fibrocystic breast changes, fibroadenoma, or a family history of breast cancer? Yes Do women have to stop OC pills every few years? No (ACOG 2001)

29. Depomedroxyprogesterone acetate (DMPA) Disadvantages 1. High incidence of amenorrhoea or menstrual irregularity 2. Weight gain 3. Slow return of fertility after discontinuation Advantages 1. Convenient - one injection/3 months 2. Can be used in women with contraindications to oestrogens

30. Monthly Injectables Cyclofem – 25 mg DMPA amd 5 mg E2 cypionate Mesigyna – 50 mg NET EN amd 5 mg E2 valerate Perlutan – 150 mg dihydroxyprogesterone acetophenide + 10 mg E2 enanthate Given monthly +/- 3 days

31. Monthly injectables Highly effective with pregnancy rates <1/HWY More regular cycle patterns 60-70% have regular cycles (compared to less than 10% in women on DMPA) Cannot be used for women with contra-indications for oestrogens

32. Progestogen implants Capsules containing levonogrestrel implanted under skin Low failure rate (<1/100WY) Most common side effect: excessive bleeding and intermenstrual bleeding Rapid return of fertility on removal Minimal metabolic effects

33. The Implanon rod The design of a single rod that provides controlled release of etonogestrel over three years requires high-tech knowledge. An AKZO-Nobel business unit specialized in fibers discovered that a copolymer called EVA ( ethylene vinyl acetate) appeared to be suitable for holding a hormonal substance and releasing it in a controlable manner. Crystals of etonogestrel are suspended in a polymer matrix of EVA to form a core. This core is then encased in an EVA membrane. This composition allows sustained release of etonogestrel from an implant with a smaller surface area than the previously known implants.The design of a single rod that provides controlled release of etonogestrel over three years requires high-tech knowledge. An AKZO-Nobel business unit specialized in fibers discovered that a copolymer called EVA ( ethylene vinyl acetate) appeared to be suitable for holding a hormonal substance and releasing it in a controlable manner. Crystals of etonogestrel are suspended in a polymer matrix of EVA to form a core. This core is then encased in an EVA membrane. This composition allows sustained release of etonogestrel from an implant with a smaller surface area than the previously known implants.

34. Contraceptive efficacy No pregnancies were observed in all 2,300 Implanon users, in an observation of more than 73,000 cycles. This demonstrates that Implanon is a highly efficacious contraceptive implant with a Pearl index of 0 (95% confidence interval 0.00-0.07). This Pearl index emphasizes the unsurpassed contraceptive protection of Implanon. If pregnancies occur during the use of a long-term contraceptive, it is difficult to describe an exact Pearl index. Especially since the contraceptive efficacy seems to depend on the duration of use, which with Norplant is 5 years: The data shown here are not comparative. In our trials, no pregnancies were observed for either Norplant or Implanon. Data from the Norplant studies show that in the first year of Norplant use 24 pregnancies occurred among more than 150,000 cycles. This results in a Pearl index of 0.2 for the first year. In the 5th year of Norplant use 9 pregnancies occurred among more than 10,000 cycles which results in a Pearl index of 1.1.No pregnancies were observed in all 2,300 Implanon users, in an observation of more than 73,000 cycles. This demonstrates that Implanon is a highly efficacious contraceptive implant with a Pearl index of 0 (95% confidence interval 0.00-0.07). This Pearl index emphasizes the unsurpassed contraceptive protection of Implanon. If pregnancies occur during the use of a long-term contraceptive, it is difficult to describe an exact Pearl index. Especially since the contraceptive efficacy seems to depend on the duration of use, which with Norplant is 5 years: The data shown here are not comparative. In our trials, no pregnancies were observed for either Norplant or Implanon. Data from the Norplant studies show that in the first year of Norplant use 24 pregnancies occurred among more than 150,000 cycles. This results in a Pearl index of 0.2 for the first year. In the 5th year of Norplant use 9 pregnancies occurred among more than 10,000 cycles which results in a Pearl index of 1.1.

35. Bleeding patterns The overall bleeding pattern seen during Implanon® use is characterized by less bleeding compared to - use of Norplant® - use of COCs - and no use of hormonal contraception. In addition, a more varied pattern can be observed. Reference period 1 is excluded from the analyses because the description of the bleeding pattern would be influenced by the menstrual period in which the implant is inserted. In each reference period, on average, 20.8% (which is the mean of reference period 2-8) of the women who used Implanon had amenorrhea. The incidence of amenorrhea with Implanon was significantly higher compared to Norplant. The incidences of infrequent, frequent and prolonged B-S were somewhat higher among Implanon users, but the differences were not statistically significant.The overall bleeding pattern seen during Implanon® use is characterized by less bleeding compared to - use of Norplant® - use of COCs - and no use of hormonal contraception. In addition, a more varied pattern can be observed. Reference period 1 is excluded from the analyses because the description of the bleeding pattern would be influenced by the menstrual period in which the implant is inserted. In each reference period, on average, 20.8% (which is the mean of reference period 2-8) of the women who used Implanon had amenorrhea. The incidence of amenorrhea with Implanon was significantly higher compared to Norplant. The incidences of infrequent, frequent and prolonged B-S were somewhat higher among Implanon users, but the differences were not statistically significant.

36. Complications (Comparative trials, meta-analysis) Complications with insertion and removal rarely occurred. With Implanon, complications with insertion were reported in 0.3% of insertions (bleeding, rod following the needle out of the skin) and 0.6% of removal (1 case of excessive fibrosis). With Norplant, there were no complications reported at insertion. In 6% of Norplant removals complications were reported (broken capsules in 4 cases, 1 case excessively time consuming, 1 case 3 capsules could not be found, 1 case a second incision was necessary)Complications with insertion and removal rarely occurred. With Implanon, complications with insertion were reported in 0.3% of insertions (bleeding, rod following the needle out of the skin) and 0.6% of removal (1 case of excessive fibrosis). With Norplant, there were no complications reported at insertion. In 6% of Norplant removals complications were reported (broken capsules in 4 cases, 1 case excessively time consuming, 1 case 3 capsules could not be found, 1 case a second incision was necessary)

37. Post-coital contraception Emergency - intercourse unexpected rape failure of barrier methods Regular - not a good method because of high failure rate and side effects

38. Yuzpe regimen 2 tablets of OC pills (100 ?g EE 1 mg norgestrel) within 72 hours of coitus Another 2 tablets 12 hours later Pregnancy rates 0.2% - 2.6% Nausea 50% Vomiting 20-25%

39. Randomised comparison of Yuzpe regimen with LNG Yuzpe LNG No of subjects 424 410 Pregnancy rates whole group 3.5% 2.9% No further coitus 2.7% 2.4% Ho & Kwan 1993

45. Pregnancy rates by further acts of intercourse Further Acts of intercourse No Yes Yuzpe 1.9% 5.3% LNG 0.8% 1.6%

47. Mifepristone (RU 486) Antiprogestin which blocks the action of progesterone Used in inducing abortions Highly effective in emergency contraception even at a very low dose (10 mg) which does not cause abortion

48. Post-coital insertion ofCopper I.U.C.D. Advantages: 1. Highly effective pregnancy rate <0.1% 2. Can be used 5 days after intercourse 3. Continued contraception Disadvantages: Bleeding; pain; infection

49. Emergency Contraception 1. Effective and safe methods are now available but they are underutilized 2. Need to remove barriers - Education - Improve access

50. TOP in first trimester 1. Surgical methods Suction evacuation 2. Medical method (<9 wks) Mifepristone (RU486) + PG

51. Regimen of medical abortion with mifepristone and PG analogue Mifepristone PG analogue Follow up

52. Medical abortion with mifepristone & PG For TOP up to 9 weeks Misoprostol is commonly used now Complete abortion rate over 95% The process resembles miscarriage: abdominal pain, bleeding and expulsion of products of conception

53. Complicationsof Sterilization 1. Complications due to laparoscopy or laparotomy - visceral damage; bleeding; wound complications including pain and infection 2. Failure (about 1 in 200 lifetime risk) 3. Ectopic pregnancy Mortality rate 1 in 10,000

54. Vasectomy Advantages 1. Simple and quick operation requiring less skill 2. Local anaesthesia 3. Less complication 4. Easier to reverse Disadvantage Not immediately effective - 2 negative semen tests at 8 and 12 weeks

55. Long term health risks of vasectomy Men can be reasssured that there is no substantial long-term health risk associated with vasectomy but they should be informed about the possibility of chronic testicular pain after vasectomy. The pain is generally mild and only rarely requires further medical or surgical intervention. RCOG 1999

56. Other new developments Hormonal patch Vaginal rings Male pills