A three-dimensional study of endometrial microvessels in women using the contraceptive subdermal levonorgestrel implant system, norplant®

Simbar, Masoumeh; Manconi, Frank; Markham, Robert; Hickey, Martha; Fraser, Ian S.

doi:10.1016/j.micron.2004.01.005

Cited by 18 publications

(8 citation statements)

References 24 publications

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“…Dilated vessels, as well as endothelial cell columns without any lumen, and without basement membrane components, were demonstrated in a three-dimensional study of vessels in the endometrium of Norplant users. 21 Similar vascular changes were also seen in the present study. Dilated vessels have been reported in the endometrium of users of long-acting progestogen-only contraceptives, such as Norplant, and the levonorgestrelreleasing intrauterine system in other studies.…”

Section: Discussionsupporting

confidence: 90%

A comparative study of Cyclofem<SUP>®</SUP> and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature

Simbar¹,

Tehrani²,

Hashemi³

et al. 2007

j fam plann reprod health care

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Objectives The most common reason for discontinuation of long-acting progestogen-only contraceptives is irregular bleeding following local endometrial vascular changes. To reduce unpredictable bleeding episodes among depot medroxyprogesterone acetate (DMPA) users, the combined injectable contraceptive, Cyclofem ® , was offered as an alternative. However, there is a gap in our knowledge about the effects of Cyclofem on the endometrial vasculature and patterns of bleeding. This study aimed to compare the effects of Cyclofem and DMPA on endometrial vascular density, endometrial histology and pattern of bleeding.Methods Sixty-eight healthy women with regular menstrual bleeding and seeking injectable long-acting contraceptives were recruited. Two endometrial samples (before and 3 to 6 months after initial exposure to DMPA or Cyclofem) were collected from each participant. The samples were stained using an immunohistochemical method and anti-CD34 to visualise the endometrial vasculature. Endometrial vascular density was assessed using standard techniques.Results Sixty-eight women were randomly assigned to Cyclofem (38 women) or DMPA (30 women). Endometrial vascular density was 149.3 ± 6.7 (mean ± SD)/mm 2 before 271 IntroductionProgestogen-only contraceptives provide a safe and highly effective method of fertility regulation. Unfortunately, they are commonly associated with the problem of endometrial breakthrough bleeding, often leading to discontinuation of use. 1 Depot medroxyprogesterone acetate (DMPA) is an aqueous suspension of pregn-4-ene-3,20-dione,17-(acetyloxy)-6-methyl-(6α) administered by intramuscular injection (150 mg once every 3 months) for long-term contraception. MPA is detected in the serum within 30 minutes following injection. Serum concentrations generally plateau at about 1.0 ng/ml for about 3 months, after which there is a gradual decline. injection. This significantly decreased to 132.4 ± 12.2 after DMPA use, and from 151.9 ± 5.8 to 131.8 ± 12.8 vessels/mm 2 following Cyclofem use (paired t-test, p<0.05). However, there was no significant difference between endometrial vascular density during treatment with Cyclofem or DMPA. Total bleeding days in the first and second 3-month time intervals were 28 ± 23 and 18 ± 12 days in DMPA users and 22 ± 14 and 16 ± 9 days in Cyclofem users, respectively, Spotting was the most common type of bleeding experienced, and atrophic endometrium was the most common histological pattern observed in both groups.Conclusions This study demonstrated that both Cyclofem and DMPA use are associated with decreased endometrial vascular density and atrophic endometrium, in addition to irregular bleeding, mainly spotting. There was no significant difference in bleeding patterns or endometrial findings observed for these two injectable contraceptives in Iranian women. long-acting injectable method that produces a more regular vaginal bleeding pattern. The extensive literature indicates that although combined oestrogen-progestogen once-amonth injectable contraceptives ...

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Section: Discussionsupporting

confidence: 90%

A comparative study of Cyclofem<SUP>®</SUP> and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature

Simbar¹,

Tehrani²,

Hashemi³

et al. 2007

j fam plann reprod health care

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“…Although differing in their effects, these results do indicate that exogenous steroid administration may cause a disruption in normal vessel formation. This variability of vascular structure in LNG exposed endometrium compared to normal endometrium has also been shown in vitro, in 3-dimensional culture systems [31]. These studies demonstrated uncannulated clumps of endothelial cells continuous with vessel-like structures.…”

Section: Progestogen Effects On Endometrial Blood Vesselssupporting

confidence: 66%

Progestogen only contraception and endometrial break through bleeding

Smith

Critchley

2005

Angiogenesis

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Progestogen only contraceptives (POC) provide a safe and effective method of fertility regulation. Unfortunately, they are commonly associated with the problem of endometrial break through bleeding (BTB), often leading to discontinuation of use. An increase in endometrial vascular fragility has been demonstrated as an important mechanism that contributes to BTB but our understanding of the interaction between exogenous steroid use and endometrial vasculature remains incomplete. This review sets out to describe a number of commonly used POC, their effects on endometrial morphology and possible molecular and cellular mechanisms that may lead to unscheduled bleeding.

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“…In some studies, reconstituted 3D visualization of the partial endometrial structures was performed by using computerized two-dimensional binary images of serial sections or multiphoton excitation microscopy (Manconi et al, 2003;Manconi et al, 2001;Simbar et al, 2004). However, these studies had serious limitations in that the observable depth was less than 120 μ m because of tissue transparency and could not detect the detailed 3D structure of the endometrial gland.…”

Section: Discussionmentioning

confidence: 99%

Three-dimensional understanding of the morphological complexity of the human uterine endometrium

Yamaguchi

Yoshihara

Suda

et al. 2020

Preprint

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The histological basis of the human uterine endometrium has been established by 2D observation. However, the fundamental morphology of endometrial glands is not sufficiently understood because these glands have complicated winding and branching patterns. To construct a big picture of endometrial gland structure, we performed tissue-clearing-based 3D imaging of human uterine endometrial tissue. Our 3D immunohistochemistry and 3D layer analyses revealed that endometrial glands formed a plexus network in the stratum basalis, similar to the rhizome of grass. We then extended our method to assess the 3D morphology of adenomyosis, a representative "endometrium-related disease", and observed 3D morphological features including direct invasion of endometrial glands into the myometrium and an ant colony-like network of ectopic endometrial glands within the myometrium. Thus, 3D analysis of the human endometrium and endometrium-related diseases will be a promising approach to better understand the pathologic physiology of the human endometrium. lives of women from puberty until after menopause (Garcia-Solares et al., 2018;Koninckx et al., 2019;Morice et al., 2016). However, the pathogenesis of endometrium-related diseases remains unclear, and further investigations focusing on the endometrium from the standpoint of disease prevention are required.The conventional morphological theory of endometrial structure has been established based on two-dimensional (2D) histological observation (Johannisson et al., 1982;McLennan and Rydell, 1965;Noyes et al., 1950). Histologically, the endometrium is lined by a simple luminal epithelium and contains tubular glands that radiate through endometrial stroma toward the myometrium via coiling and branching morphogenesis (Gray et al., 2001). The human endometrium is stratified into two zones:the stratum functionalis and the stratum basalis. The stratum functionalis is shed during menstruation and regenerates from an underlying basal layer during the proliferative period. Therefore, it is widely assumed that regeneration of the stratum functionalis depends on endometrial progenitor/stem cells residing in the stratum basalis (Kyo et al., 2011;Maruyama and Yoshimura, 2012;Padykula, 1991;Prianishnikov, 1978). Despite this well-established understanding, neither the detailed mechanisms of endometrial regeneration during the menstrual cycle nor the localization of endometrial progenitor/stem cells have been fully characterized (Garry et al., 2010;Gellersen and Brosens, 2014;Santamaria et al., 2018). One of the reasons for this knowledge gap is that the fundamental structure of the human endometrium has not been sufficiently clarified. Since human endometrial glands have complicated winding and branching morphologies, it is extremely difficult to assess the whole shapes of glands by only 2D histopathology imaging.In our previous genomic study, sequence analysis of 109 single endometrial glands revealed that each gland carried distinct somatic mutations in cancer-associated genes such as PIK3CA, KRAS...

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A three-dimensional study of endometrial microvessels in women using the contraceptive subdermal levonorgestrel implant system, norplant®

Cited by 18 publications

References 24 publications

A comparative study of Cyclofem<SUP>®</SUP> and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature

A comparative study of Cyclofem<SUP>®</SUP> and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature

Progestogen only contraception and endometrial break through bleeding

Three-dimensional understanding of the morphological complexity of the human uterine endometrium

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