Conception to ongoing pregnancy: the 'black box' of early pregnancy loss

Macklon, Nick S.; Geraedts, J. P. M.; Fauser, Bart C.J.M.

doi:10.1093/humupd/8.4.333

Cited by 652 publications

(467 citation statements)

References 116 publications

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“…Sub-optimal conditions for embryo culture mean that it was 109, 110 and probably still is 111 doubtful that reliable values can be extrapolated from laboratory in vitro to natural in vivo circumstances 20 . Importantly, the reproductive stages are also altered.…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, “ poor estimates of fertilization failure rate and the mortality at 2 weeks after fertilisation ” 15 drawn “ from unusual or biased samples ” 134 indicate that the “black box” of early pregnancy loss 20 is not as wide open as has been thought.…”

Section: Discussionmentioning

confidence: 99%

“…Mid-cycle elevation of hCG is associated with embryo implantation 19, 20, 55 . Early assays for the detection of hCG were probably confounded by antibody cross-reactivity with luteinizing hormone 56 but modern tests are more specific and a positive result is a reliable indicator of early pregnancy.…”

Section: What the Data Saymentioning

confidence: 99%

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Early embryo mortality in natural human reproduction: What the data say

Jarvis

2016

F1000Res

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It is generally accepted that natural human embryo mortality during pregnancy is high – losses of 70% and higher from fertilisation to birth are frequently claimed. The first external sign of pregnancy occurs two weeks after fertilisation with a missed menstrual period. Establishing the fate of embryos before this is challenging, and hampered by a lack of data on the efficiency of fertilisation under natural conditions. Four distinct sources are cited to justify quantitative claims regarding embryo loss: (i) a hypothesis published by Roberts & Lowe in The Lancet is widely cited but has no quantitative value; (ii) life table analyses give consistent assessments of clinical pregnancy loss, but cannot illuminate losses at earlier stages of development; (iii) studies that measure human chorionic gonadotrophin (hCG) reveal losses in the second week of development and beyond, but not before; and (iv) the classic studies of Hertig and Rock offer the only direct insight into the fate of human embryos from fertilisation under natural conditions. Re-examination of Hertig’s data demonstrates that his estimates for fertilisation rate and early embryo loss are highly imprecise and casts doubt on the validity of his numerical analysis. A recent re-analysis of hCG study data suggests that approximately 40-60% of embryos may be lost between fertilisation and birth, although this will vary substantially between individual women. In conclusion, it is clear that some published estimates of natural embryo mortality are exaggerated. Although available data do not provide a precise estimate, natural human embryo mortality is lower than is often claimed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Early embryo mortality in natural human reproduction: What the data say

Jarvis

2016

F1000Res

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Section: Epidemiologymentioning

confidence: 99%

“…An estimated 30% of human conceptions are lost prior to implantation and a further 30% following implantation but before the missed menstrual period, that is in the third or fourth week of gestation. These are often termed preclinical losses [11].The risk of sporadic miscarriage between 6 and 12 weeks of gestation in women less than 35 years of age is 9% to 12%. The risk increases with age.…”

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confidence: 99%

Recurrent Miscarriage: A Review

Barrenetxea¹

2017

RMGO

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pregnancy events [2]. Clinical miscarriages may be subdivided into early clinical pregnancy losses (before gestational week 12) and late clinical pregnancy losses (gestational weeks 12 to 21). The term miscarriage is preferred rather than abortion both by patients and physicians, although "spontaneous abortion" is still used in scientific literature [3,4].For more than 30 years, controversy has existed on the number of miscarriages required to define RM and when diagnostic testing is warranted [5] EpidemiologyEarly pregnancy loss is perhaps the most common obstetric complication, occurring in over two-thirds of human conceptions. Approximately 15 -20% of all clinically recognized pregnancies will end in a miscarriage [4,9,10]. However, prospective cohort studies using sensitive and specific daily urinary hCG assays in women trying to conceive have demonstrated that only around one-third of conceptions progress to a live birth. Most of the losses occur before the clinical recognition of pregnancy as implantation failures. An estimated 30% of human conceptions are lost prior to implantation and a further 30% following implantation but before the missed menstrual period, that is in the third or fourth week of gestation. These are often termed preclinical losses [11].The risk of sporadic miscarriage between 6 and 12 weeks of gestation in women less than 35 years of age is 9% to 12%. The risk increases with age. In women older than 40 years of age, the sporadic miscarriage rate approaches 50%. Late losses between 12 and 22 weeks occur less frequently and constitute around 4% of pregnancy outcomes [4,9].Compared to sporadic miscarriage the prevalence of RM is considerably lower irrespective of whether biochemical losses are included or not. Approximately 1% of all women trying to conceive have recurrent miscarriage, defined as three previous miscarriages; when recurrent miscarriage is defined as two previous miscarriages, the proportion rises to 3% [12,13]. EtiologyMultiple potential etiologies for RM have been described (Table 1). As a consequence, several recommendations have been published regarding the evaluation and management of RM [3].The potential etiologies of RM can be divided into embryologically driven causes (mainly due to an abnormal embryonic karyotype) and maternally driven causes which affect the endometrium and/or placental development [14,15]. Thus, studies that focus on RM have Barrenetxea G, et al., J Reprod Med Gynecol Obstet 2017 AbstractHuman reproduction is characterized by its inefficiency. The loss of pregnancy at any stage can be a devastating experience and particular sensitivity is required in assessing and counseling couples with Recurrent Miscarriage (RM). Recurrent Miscarriage (RM) represents a clinical challenge for physicians not only because there are multiple possible etiologies, but also because the diagnostic testing is costly and time consuming. Despite several well-known etiologic factors, the cause of RM cannot be determined in almost 50% of cases. Multiple potential etiolo...

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Plan B and the Politics of Doubt

Davidoff

Trussell²

2006

JAMA

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Conception to ongoing pregnancy: the 'black box' of early pregnancy loss

Cited by 652 publications

References 116 publications

Early embryo mortality in natural human reproduction: What the data say

Early embryo mortality in natural human reproduction: What the data say

Recurrent Miscarriage: A Review

Plan B and the Politics of Doubt

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