A.M. Salvatierra

Treatment with NORPLANTR subdermal implants inhibits sperm penetration through cervical mucus in vitro

Attempts were made to collect several samples of cervical mucus in each of thirty-three cycles of women using NORPLANT subdermal implants, in seven cycles from NORPLANT-2 rod users, and in 33 control cycles. The attempts to collect a mucus sample were successful on 20 of 77 and 7 of 14 occasions in NORPLANT capsule and rod users, respectively, due to the scanty amount and stickiness found in the majority. All 59 attempts in control subjects were successful. The distance travelled by the fastest sperm and by the bulk of spermatozoa through the cervical mucus in vitro was assessed after 10 min of incubation with a normal semen sample. The best score for each cycle was considered for the comparison between treated and control cases. Sperm penetration was greatly impaired in mucus samples of implant users with penetration by the fastest sperm exceeding 10 mm in only two instances and exceeding 20 mm in none. In 30 of 33 control samples, the fastest sperm travelled 21 mm or more and in 28, the bulk of spermatozoa travelled further than 10 mm. Unsuccessful attempts to collect mucus and poor sperm migration were observed in NORPLANT implant users even when circulating estradiol levels were comparable to those seen in the late follicular phase of the normal menstrual cycle. These results suggest that the principal mechanism by which NORPLANT implants prevent pregnancy is by interference of sperm migration through cervical mucus.

FERTILITY REGULATION IN NURSING WOMEN: IV. Long-Term Influence of a Low-Dose Combined Oral Contraceptive Initiated at Day 30 Postpartum Upon Lactation and Infant Growth

The study was designed to test the long-term influence of a low-dose combined oral contraceptive upon lactation and infant growth when treatment was initiated at day 30 postpartum. The contraceptive tested contained ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg. Two control groups were formed by women who received an injectable placebo or a Copper T at day 30 postpartum. Women in the injectable placebo group received non-hormonal contraceptives at day 90 postpartum. An exacting list of requirements for admission and continuation in the study was applied to all groups. The oral contraceptive group had a significantly lower percentage of cases in full nursing from the 4th through the 10th postpartum month when compared to both control groups. The average absolute weight of infants in the oral contraceptive group was significantly lower at several ages when compared to the placebo group but not when compared to the Copper T group. No adverse side effects upon infants health were detected. It was concluded that the oral contraceptive tested showed a moderate inhibitory influence upon lactation when treatment was initiated at the beginning of the second postpartum month.

Lactational amenorrhea and the recovery of ovulation and fertility in fully nursing Chilean women

The probability of experiencing the first postpartum bleeding, the first ovulation and the risk of pregnancy during exclusive breastfeeding was assessed in a selected group of urban Chilean women. Admission criteria included having had a normal pregnancy and a vaginal term delivery of a healthy infant and the desire to maintain breastfeeding for as long as possible. The risk of bleeding and the recovery of ovulation was assessed in 48 women selected for being amenorrheic and fully nursing at day 75 postpartum and their willingness to participate in the blood sampling protocol. The first bleeding and ovulation was experienced while fully nursing by 28% and 26% of these subjects, respectively, at day 180 postpartum. The probability of experiencing the first bleeding and the probability of pregnancy during full nursing were calculated for 236 women not contracepting who were enrolled during the first month postpartum. The cumulative probability of bleeding and of pregnancy was 52% and 9.4% at day 180 postpartum, respectively. The risk of pregnancy was less than 2% in the subset of amenorrheic cases. In this urban population selected for having the highest motivation and best breastfeeding performance, the association of breastfeeding with infertility was too weak to serve as an effective birth spacer, except for the period of lactational amenorrhea. When the first postpartum bleeding took place before the sixth postpartum month in fully nursing women, it had a good predictive value to indicate the onset of a higher risk period.

Fertility regulation in nursing women: VIII. Progesterone plasma levels and contraceptive efficacy of a progesterone-releasing vaginal ring

The objectives of this trial were to test the contraceptive efficacy and measure progesterone plasma levels of women using progesterone-releasing rings during lactation. Two types of rings delivering an average of about 5 mg or 10 mg of progesterone per day were tested in 128 healthy nursing women. A control group was formed by 127 Copper T users. Rings were inserted at day 60 postpartum and replaced every 3 months with a new one. Initially progesterone plasma levels were around 10 nmol/l and 15 nmol/l for rings releasing 5 and 10 mg per day, respectively, and decreased slightly after 30 days. Levels observed in subsequent segments of use approximated those of the first segment. These levels are within the range shown to inhibit fertility in lactating women. One pregnancy was diagnosed in 739 woman-months of progesterone ring use, and none occurred in 794 woman-months of Copper T use, which contrasts with the high incidence of pregnancy in a group of untreated nursing women where 19 pregnancies resulted during 677 woman-months. No deleterious effects were detected lactation and infant growth or maternal and infant health. It is concluded that the vaginal rings releasing progesterone are a suitable contraceptive method for lactating women.

Fertility regulation in nursing women: VII. Influence of NORPLANTR: Levonorgestrel implants upon lactation and infant growth

The objective of this study was to test the influence of NORPLANT implants upon lactation and infant growth. The results obtained during the first postpartum year are reported. One-hundred women were enrolled in the implant group. The control group was formed by 100 women who received a Copper T IUD. Treatments were administered at day 55 +/- 3. At admission all subjects were in exclusive breastfeeding with an adequate weight increase of the infant. No significant differences were found between the treated and control groups in the percentage of women in full nursing at different postpartum intervals, except for the 12th month postpartum where a lower percentage of cases from the NORPLANT group was in the full nursing category. No difference was found in the time of weaning. The infants showed a normal weight gain rate in both groups although the girls from the NORPLANT group showed a significantly lower daily weight increase during the 4th month than the girls from the IUD group. No pregnancies were diagnosed. No women asked for implant removal during the first year. No serious side effects related to treatment were detected. Bleeding irregularities were rare during breastfeeding which is in contrast with what occurs in non-nursing women treated with NORPLANT implants. Levonorgestrel concentrations found in milk were variable and individual values ranged from 23 to 311 pg/ml. The dose received by the infant can be estimated around 15 to 18 ng/Kg/day during the first month of treatment when the higher plasma values of levonorgestrel are observed. These levels is conjunction with the clinical observations reported here minimize the potential problems associated with levonorgestrel transference through maternal milk. Nevertheless, long-term studies are required to settle this matter and until more information is available, NORPLANT implant use in lactating women should be limited to cases who require a highly effective contraceptive method and where non-hormonal methods of similar effectiveness are contraindicated or unacceptable.

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.

Fertility regulation in nursing women: III. Short-term influence of a low-dose combined oral contraceptive upon lactation and infant growth

The study was designed to test the short-term influence of a low-dose combined oral contraceptive upon lactation and infant growth when treatment was initiated at day 30 postpartum. The contraceptive tested contained ethinyl estradiol 0.03 mg and levonorgestrel 0.15 mg. Two control groups were formed by women who received either an oral placebo or an injectable placebo at day 30 postpartum. An exacting list of requirements for admission and continuation in the study was applied to all groups. The oral contraceptive group had a lower percentage of cases in exclusive breastfeeding at day 91 postpartum when compared to both control groups. Infants in the oral contraceptive group showed a significantly lower average absolute weight at days 61 and 91 postpartum and a significantly lower average daily weight increase during the first month of treatment when compared to both control groups. It was concluded that the oral contraceptive tested had a negative influence upon lactation and child growth.

Fertility regulation in nursing women. II. Comparative performance of progesterone implants versus placebo and copper T.

A clinical study was designed to test whether sustained administration of progesterone to nursing mothers could prolong lactation and delay the postpartum recovery of fertility. The hormone was administered by subdermal implantation of six pellets that each contained 100 mg of progesterone. This treatment was administered to 84 fully nursing women on day 30 post partum. Control groups were composed of 130 fully nursing women who received an injectably placebo, and by 125 fully nursing women who received a TCu 200 intrauterine contraceptive device. An exacting list of requirements for admission to and continuation in the study was applied to all groups. No pregnancies occurred in the progesterone-treated group from the second to the sixth postpartum month. This period coincided with the period of elevation plasma progesterone attributable to hormone released from the implants. The cumulative probability of pregnancy in the placebo group was 10.2 per 100 women at the sixth month. Treatment with progesterone did not change the duration of lactation or the rate of child growth, and no adverse effects were recorded. These results warrant further investagation of the use of progesterone as an alternative method to prevent conception in nursing women.

Fertility regulation in nursing women. VI. Contraceptive effectiveness of a subdermal progesterone implant.

Six progesterone pellets implanted subdermally were tested as contraceptive method for lactating women. One pregnancy was diagnosed in 1614 woman-months of observation, a failure rate which was similar to that observed in a contemporary group of Copper T users. Nineteen pregnancies were diagnosed in the 677 woman-months observed in untreated lactating women. The progesterone implants were effective when administered either at 30, 60 or 240 days after delivery. The duration of the effective life was 5 months and fertility was quickly restored afterwards. There were no deleterious effects upon maternal or infant health or upon lactation and the rate of child growth. The main problem encountered was the occurrence of pellet expulsion at a variable rate which appeared related to the manufacturing procedure.

Endocrine response and ovum transport in women treated with d-Trp6–luteinizing hormone–releasing hormone in the postovulatory period

Possible alterations in ovum transport during increased activity of the hypothalamic-pituitary-ovarian axis were investigated in women. D-Trp6-luteinizing hormone (LH)-releasing hormone, a synthetic peptide with potent gonadotropin-releasing activity, was used to induce a gonadotropin surge and stimulate ovarian steroid secretion in the postovulatory phase. The compound was administered intramuscularly or intravenously 24, 48, or 72 hours following the maximum preovulatory LH level in plasma in seven women. An immediate and pronounced gonadotropin surge accompanied by a moderate increase in the estradiol and progesterone level was obtained in all cases. Ova were recovered from the fallopian tubes in four of the seven women 24 hours following treatment. The rate of recovery and the location of ova within the genital tract indicate that the treatment and the resulting endocrine changes failed to accelerate migration of the ova toward the uterus. This observation, taken together with other negative findings previously reported, suggests that in comparison with other mammals transport of the ovum in the woman is relatively insensitive to endocrine changes occurring in the postovulatory phase.