Levonorgestrel IUD: is there a long-lasting effect on return to fertility?

Abstract

Intrauterine devices (IUDs) are effective and safe long-acting reversible contraceptive methods for preventing unplanned pregnancies. While extensive studies were conducted to evaluate return to fertility after removal of IUDs, majority of them were focused on multiparous women using copper IUDs. Current trends indicate increased use of levonorgestrel (LNG) IUDs in nulliparous women for very long periods of time, with both nulliparity and long duration of LNG-IUD use being potentially associated with trends towards longer time to conception post removal. Understanding the effects that LNG-IUDs may have on endometrial morphology and gene expression has important implications to further understanding their mechanism of action. Studies examining endometrial gene expression show persistent changes in receptivity markers up to 1 year after removal of an inert IUD, and no similar studies have been performed after removal of LNG-IUDs. Given the current gap in the literature and trends in LNG-IUD use in nulliparous young women, studies are needed that specifically look at the interaction of nulliparity, long-term use of LNG-IUD, and return to normal fertility. Herein, we review the available literature on the mechanism of action of IUDs with a specific focus on the effect on endometrial gene expression profile changes associated with IUDs.

Thin endometrial lining: is it more prevalent in patients utilizing preimplantation genetic testing for monogenic disease (PGT-M) and related to prior hormonal contraceptive use?

“…In general, a quick return to normal has been described for histologic aspects of the endometrium, but long-term effects have also been described, e.g. for gene-expression profiles persisting for over 1 year after cessation ( Anderson et al , 2005 ; Dinehart et al , 2020 ). The biological basis for a lasting effect of hormonal contraceptives on the endometrial lining after cessation is not clear.…”

“…However, most studies on return to fertility after contraceptive use are reassuring, although a slight delay of several months in return to fertility after cessation of COCs has also been described ( Barnhart and Schreiber 2009 , pp. 659–663; Dinehart et al , 2020 , pp. 45–52).…”

“…It is well recognized that endometrial thinning occurs during the use of combined oral contraceptive (COC) and hormonal long-acting reversible contraceptives, such as the levonorgestrel intra-uterine device (IUD) or depot medroxyprogesteronacetate (DMPA). After prolonged use, endometrial atrophy develops ( Anderson et al , 2005 ; Grow and Iromloo, 2006 ; Dinehart et al , 2020 ). Possibly, the thinning effect of hormonal contraceptives on the endometrium lingers longer than previously anticipated.…”

Practical Recommendations on the Management of Issues Related to the Levonorgestrel 52mg Intrauterine System: A Delphi Panel

“…In addition, recently ulipristal acetate (UPA) at the dose of 5mg/5 days was compared to placebo, showing a trend of superiority over placebo in the bleeding control [26]; however, the drug is not available in Brazil. Although one-third of the panelists reported the use of COC or progestin-only pills to bleeding control, it is not supported by the evidence because it is well described that the endometrium in users of Mirena® is refractory to estrogens [27,28].…”

Effect of levonorgestrel emergency contraception on implantation and fertility: A review

“…Against this background repeated use of Levonorgestrel EC is unlikely to affect future fertility. Three systematic reviews on future fertility after contraceptive use have all concluded that Levonorgestrel containing contraceptives, irrespective of parity, gravidity or duration of use, have no detrimental effect on time to pregnancy or fecundity compared to nonhormonal methods and that conception rates are similar to those expected in the general population [67][68][69] .…”