H. Cárdenas

Contraceptive efficacy of lactational amenorrhea in urban Chilean women

The contraceptive efficacy of breastfeeding was assessed in 236 healthy urban women who were followed at monthly intervals during the first postpartum year. Proportional hazard models were used to evaluate the influence of time postpartum, menstrual status and breastfeeding pattern upon the risk of pregnancy. Time and menstrual status had a highly significant effect on this risk. Those women who remained in amenorrhea had cumulative probabilities of pregnancy of 0.9% and 17% at 6 and 12 months postpartum, respectively. In those who recovered menstrual cycles, the risk rose to 36% and 55% at 6 and 12 months, respectively. Milk supplementation also increased significantly the risk when considered alone but not when time and/or menstrual status were included in the analysis. However, amenorrheic women who introduced bottle feeding, had a higher risk of pregnancy after 6 months postpartum than those who remained fully nursing. The analysis was unable to detect a significant influence of the nursing frequency. The results confirm that lactational amenorrhea is an effective contraceptive during the first six months postpartum. The first postpartum bleeding marks a great increase in the risk of pregnancy. Supplementation also increases the risk, particularly in amenorrheic women.

Relative contributions of anovulation and luteal phase defect to the reduced pregnancy rate of breastfeeding women

OBJECTIVEnTo evaluate the contribution of anovulation and luteal phase defects to lactational infertility.nnnDESIGNnProspective longitudinal follow-up.nnnSETTINGnOutpatient clinic.nnnSUBJECTSnForty-nine women fully nursing and amenorrheic on day 75 postpartum and 25 cycling, interval non-nursing women.nnnINTERVENTIONSnPlasma prolactin, luteinizing hormone, estradiol (E2), and progesterone (P) levels twice a week up to the second postpartum menses.nnnMAIN OUTCOME MEASURESnOvulation rate and endocrine profile of the menstrual cycles.nnnRESULTSnOvulation rates were 37% and 97% at 6 and 12 months postpartum; 67% of ovulations occurred in amenorrhea. The luteal phase was shorter, and E2 and P levels were lower in lactating women than in non-nursing women. These parameters were closer to normal in the second cycle than the first, in spite of active nursing. The risk of ovulation and pregnancy in amenorrhea was 27.7% and 0.9% at month 6 postpartum. After the first menses, these risks were 93% and 7%, respectively.nnnCONCLUSIONnThe abnormal endocrine profile of the first luteal phase offers effective protection to women who ovulate during lactational amenorrhea within the first 6 months after delivery. Later luteal phases are improved and women are at risk of pregnancy.

Recovery of fertility and outcome of planned pregnancies after the removal of NORPLANTR subdermal implants or Copper-T IUDs

The recovery of fertility after discontinuation of NORPLANT implant use was assessed in ninety women who stated a desire for a new child at the time of removal. Three subjects were lost to follow-up after removal. The cumulative probability of conception in the remaining 87 women was 25, 49, 73 and 86 percent at one, three, six and twelve months after removal, respectively. Nine observations were censored either because of the use of a contraceptive method soon after removal of the implants (n = 7) or separation (n = 2). All other cases were pregnant at the end of two years with exception of three subjects where a male factor for infertility was present. There was no significant correlation between the length of NORPLANT use and the length of the interval from removal to conception. A significantly higher frequency of intervals longer than 6 months was observed among women older than 30 years as compared to younger women. Pathology during pregnancy was cholestasia (n = 5), hypertension (n = 1) and gestational diabetes (n = 1). The outcome was term delivery in 59 cases, premature delivery in 4 cases, and spontaneous abortion in 7 cases. One woman is still pregnant and the outcome is unknown in 4 cases. One premature infant died. A contemporary control group of Copper T users enrolled under the same criteria as NORPLANT implant users provided 44 women who had the device removed to become pregnant. The cumulative probability of pregnancy was 27, 69, 84 and 89 at one, three, six and twelve months and all were pregnant by the end of the second year. Six censored observations occurred because of the use of another contraceptive method after removal (n = 3) or loss to follow-up (n = 3). The outcome of pregnancy was term delivery in 23 cases and abortion in 7 cases. Recovery of fertility occurred at a normal rate after NORPLANT implant removal and the incidence of problems detected in the ensuing pregnancy were within the expected range for Chilean women.

Clearance of levonorgestrel from the circulation following removal of NORPLANTR subdermal implants

The disappearance of levonorgestrel from plasma after the removal of NORPLANT subdermal implants was studied in 12 women who had been treated from 5.5 to 78 months. The existence of one or two half-lives for the rate of disappearance was assessed. The influence of body weight, body fat and length of treatment upon levonorgestrel clearance was studied through stepwise regression analysis. It was found that the levonorgestrel decay rate after implant removal can be entirely accounted assuming one half-life of 42 +/- 16 h (mean +/- SD; range 13 to 62 h). Stepwise regression analysis showed that levonorgestrel half-life is positively correlated with body weight and not significantly correlated with the length of treatment or body fat. It is concluded that, after long-term administration of levonorgestrel via subdermal implants, the major part of the steroid is cleared from plasma within 96 h and that only trace amounts are detected in the following days.

A longitudinal study on cortisol, prolactin and thyroid hormones in users of norplantR subdermal implants or a copper T device

A longitudinal study was undertaken to assess PRL, cortisol, TSH, T3 and T4 levels in NORPLANT implant users (n = 22) and Copper T users (n = 20). Participants were healthy women with no contraindication for hormonal contraception. Samples were drawn at 0930 to 1000 h twice pretreatment and at month 2, 4, 6, 12, 24 and 36 after insertion. At the second treatment month, a second sample was obtained at 1600 h to assess cortisol diurnal variation. Hormones were measured by RIA. Values for all hormones were similar in Norplant and Copper T users. No significant changes occurred throughout the study period. Elevated PRL levels (greater than 500 mU/1) were found in three women from each group before and during treatment but no clinical evidence of hyperprolactinemia was detected. The results of this study reassure that long-term use of NORPLANT implants do not impair plasma levels of cortisol, prolactin and thyroid hormones.

Additive effect of RU 486 and anordrin on pregnancy interruption in the mouse

The effect of various doses of anordrin and RU 486, alone or combined, on serum progesterone (P) levels, fetal resorption, and recovery of ovulation was studied in mice. Each drug was given as a single sc injection on day 7 of pregnancy and autopsy was performed on days 8, 9, or 11. Serum P was normal at 24 h but fell significantly 48 h after treatment with anordrin (0.05 mg). Doses of 0.05 or 0.2 mg anordrin were effective in interrupting pregnancy in 30% and 70% of pregnant mice, respectively. RU 486, 0.01 mg per mouse, induced a pronounced decrease of P levels 24 h after treatment and interrupted pregnancy in 50% of pregnant mice. The combined treatment with submaximal doses of anordrin plus RU 486 did not further decrease P levels, but increased the proportion of mice with fetal resorptions to 90%. The combination of small doses of anordrin with RU 486 had an additive effect on pregnancy termination. The additive effect required a dose of RU 486 above the threshold level. Direct observation of aborted fetuses indicated that the resorptive process occurred earlier with RU 486 than with anordrin. Recovery of ovulation was associated with pregnancy termination in a high proportion of mice treated with either drug or their combination.

A STUDY ON THE FEASIBILITY OF SUPPRESSING OVARIAN ACTIVITY FOLLOWING THE END OF POSTPARTUM AMENORRHOEA BY INCREASING THE FREQUENCY OF SUCKLING

The aim of the study was to test the effect of increasing the frequency of breastfeeding upon ovarian function following the end of postpartum amenorr‐hoea. Women exclusively breastfeeding (n= 14) who experienced their first postpartum menstruation between the third and fifth month after delivery were randomly allocated to an experimental (n= 7) and a control (n= 7) group and studied during the next two cycles. Women in the experimental group agreed to increase the number of breastfeeding episodes per day throughout the second cycle. Blood samples were drawn twice a week from the first to the third postpartum menstruation for prolactin, oestradiol and progesterone determinations. The number of breastfeeding episodes per day and night and the length of each episode were recorded daily. An average frequency of 11 nursing episodes per 24 h was reported during the first study cycle in both groups. The experimental group increased by 50% the breastfeeding frequency after the second menstruation while the control group kept its spontaneous feeding pattern. The increase of suckling frequency occurred mainly during day hours. The total breastfeeding time per 24 h was not increased. The length of the menstrual cycle was not altered by the increased suckling frequency. The endocrine pattern differed neither between the first and second cycle of the experimental group nor between the experimental and control group, with the exception of PRL levels which were higher in the experimental group throughout both cycles. Twenty cycles (71%) showed progesterone values compatible with ovulation (> 9.5 nmol/l). The highest progesterone values and the highest oestradiol values observed in the ovulatory cycles of lactating women were within the range found in non‐nursing fertile women. Plasma levels of PRL were significantly elevated in all cycles but one, in comparison with PRL levels in non‐nursing women. It is concluded that if cyclic ovarian function is reestablished early in fully nursing women, a mere increase in the number of breastfeeding episodes, without augmenting total suckling time and the frequency of nocturnal episodes, does not provide a sufficient stimulus to re‐suppress the pituitary‐ovarian axis.

Inhibition of sperm migration, fertilization and implantation in rats by precoital intrauterine administration of Gossypol or Nonoxynol-9

The effects of precoital intrauterine administration of Gossypol, Nonoxynol-9 or p-Aminobenzamidine on reproductive function were investigated in rats. The drugs were instilled in one uterine horn in the evening of proestrus prior to caging with a fertile male. The opposite side was similarly treated with the vehicle and served as control. Animals were killed in the morning following mating to assess the number of spermatozoa at the site of fertilization or on days 2-3 of pregnancy to determine the proportion of penetrated oocytes or on day 12 to count implanted embryos. Gossypol 0.05 to 5 mg or Nonoxynol-9 0.1 - 10 microliter reduced the number of spermatozoa reaching the ampullae and the number of penetrated oocytes in a dose-dependent fashion. At the highest dose both compounds prevented pregnancy exclusively in the treated side. p-Aminobenzamidine at a dose of 10 mg failed to affect the proportion of penetrated eggs found on days 2 or 3 of pregnancy. The results indicate that the rat bioassay is suitable to screen agents that can affect sperm function or viability since it can discriminate between drugs and doses and disclose differential effects upon sperm migration and fertilizing capacity.