Reproductive Function During Lactation

Strategies for Mammalian Reproduction and Birth Spacing

In mammalian physiology, lactation follows pregnancy, and provision of species-specific milk is an essential part of neonatal development. However, reproductive strategies vary widely. Life history theory proposes that unfavorable conditions favor a “fast” strategy, with early sexual maturity and frequent, short pregnancies with many small offspring. Under more favorable conditions, “slow” strategies predominate, with later sexual maturity, longer pregnancies, larger offspring, and greater investment after birth through prolonged lactation and parenting ( Fig. 21.1 ). ³

While the offspring is suckling and dependent on its mother for care, fertility is suppressed, so that the mother has sufficient energy and time to care for the juvenile. Weaning occurs once the juvenile is able to survive independently; with cessation of lactation, fertility returns and the mother is able to conceive again ( Fig. 21.2A ). Primates as a group follow a slower life history pattern than many other mammals, with one or two offspring per pregnancy and a prolonged period of maternal care. Compared with nonhuman primates, humans mature later, which reduces the number of years they are able to reproduce; to compensate, anthropologist Daniel Sellen notes that humans have adapted their child-rearing strategy to allow shorter intervals between births. ⁴ , ⁵ Indeed, humans are the only primates who are able to conceive before the older sibling is able to forage for himself or herself; we rely on other caregivers and grandparents to assist with juveniles and provide transitional foods after weaning (see Fig. 21.2B ). When resources are constrained, humans may introduce supplemental feeds from birth, with adverse consequences for mother and child (see Fig. 21.2C ).

Normal interpregnancy intervals in natural fertility populations appear to have been between 2 and 3 years. In the !Kung hunter-gatherers, breastfeeding occurs continuously through age 2 to 3, with children continuing to sleep near their mothers and nurse at night for years. ¹ Sellen notes that foragers, who are able to carry their children with them, tend to wean later than subsistence farmers and herders, whose work requires separation from their infants. ⁴

With the introduction of breast-milk substitutes, it became possible to separate mother from infant at birth, allowing resumption of ovulation and pregnancy to follow almost immediately and markedly shortening interbirth intervals. However, rapid repeat pregnancies are associated with risks. In observational studies, interpregnancy intervals less than 18 months are associated with increased risks to the mother, the older child, and the next baby. A variety of mechanisms have been proposed to explain these associations. ⁶ A major objective of postpartum contraceptive counseling is to share with families the rationale for delaying the next pregnancy and assist them in selecting an appropriate contraceptive strategy.

Factors Affecting Return of Fecundity

Ovulation and return of menses occur earlier in women who do not breastfeed or breastfeed less intensively. A study in US women showed that the average time to first ovulation was 45 ± 3.8 (range 25 to 72) days in nonlactating women compared with 189 ± 14.7 (range 34 to 256) days for lactating women, as determined by urinary pregnanediol-3a-glucuronide, a progesterone metabolite ² ( Fig. 21.3 ). Among lactating women, frequency and duration of suckling were inversely correlated with return of ovulation. These findings were confirmed in a study of lactation among women in Manila and Baltimore. ⁷ A larger number of feeds per day, longer durations of feeding, and a greater percentage of feeds that were breast milk were all associated with a lower proportion of women ovulating ( Fig. 21.4 ).

Return of fecundity also varies with maternal energy balance. Lactation imposes a substantial metabolic load on the mother, estimated at 597 to 716 kcal (2.5 to 3 MJ) per day. ⁸ Valeggia and Ellison ⁹ propose that the lactating mother cannot “afford” to ovulate unless she has access to sufficient nutrition to sustain herself, her infant, and another pregnancy. These authors studied return of ovulation among well-nourished Toba women in Argentina and found that positive energy balance, indexed by rising C-peptide levels and increasing body mass index (BMI) ( Fig. 21.5 ), precedes return of menses, which occurred at a mean of 10.2 ± 4.3 months postpartum. ⁹ , ¹⁰ , ¹¹ , ¹² In a study in Sri Lanka, higher BMI was associated with earlier return of menses, providing further support for the importance of energy balance in duration of amenorrhea. ¹³

A large international study (N=4118 mother-infant pairs) by the World Health Organization (WHO) Task Force on Methods for the Natural Regulation of Fertility quantified non–feeding-related and feeding-related characteristics associated with time to return of menses. ¹⁴ Lower maternal BMI, a higher number of prior live births and more episodes of infant illness were associated later return of menses. Infant factors independently associated with longer amenorrhea included shorter time between birth and first breastfeed, later introduction of regular supplementation, longer total duration of breastfeeding in 24 hours and greater percentage of feeds that were breast milk. For women who were fully breastfeeding and whose menses had not returned, the 6-month pregnancy rate was 1.0% (95% confidence interval [CI] 0 to 2.1) and the 12-month pregnancy rate was 6.9% (95% CI 2.0 to 11.8). ¹⁵

Physiology of Fertility Suppression

Ovulatory cycles require the coordinated activity of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Pulsatile release of GnRH from the hypothalamus stimulates pituitary production of LH and FSH, which promote maturation of ovarian follicles, ovulation, and production of progesterone from the ovarian corpus luteum. Estrogen and progesterone in turn stimulate proliferation and secretory differentiation of the endometrium to support a pregnancy, should fertilization occur.

Lactation appears to suppress ovulation through multiple mechanisms. Emerging evidence suggests that the neuropeptide kisspeptin, encoded by the Kiss1 gene, may play a central role in lactation-associated fertility suppression, both through prolactin receptors on kisspeptin neurons and through sensory input from suckling. ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ Moreover, kisspeptin neurons are modulated by nutritional status, and food restriction during lactation in rodents downregulates Kiss1 mRNA expression and delays return of fertility. ²² , ²³ Although animal studies demonstrate lactation-related differences in kisspeptin expression, a small study in women with lactational amenorrhea did not find differences in plasma kisspeptin levels compared with normally cycling women. ²⁴

Lactation may also suppress ovulation at the level of the pituitary and the ovary. In a longitudinal study of women with lactation amenorrhea, follicular growth was observed, but levels of estradiol and both inhibin A and B were much lower than during ovulatory cycles. ²⁵ Although circulating levels of FSH were similar during lactational amenorrhea and ovulatory cycles, the isoforms of FSH during lactational amenorrhea were more acidic, reflecting posttranslational modifications that may reduce the bioactivity of circulating FSH. ²⁶