Peri‐implantation urinary hormone monitoring distinguishes between types of first‐trimester spontaneous pregnancy loss

Abstract

Background Lutenising hormone (LH) and human chorionic gonadotropin (hCG) hormone are useful biochemical markers to indicate ovulation and embryonic implantation, respectively. We explored “point‐of‐care” LH and hCG testing using a digital home‐testing device in a cohort trying to conceive. Objective To determine conception and spontaneous pregnancy loss rates, and to assess whether trends in LH‐hCG interval which are known to be associated with pregnancy viability could be identified with point‐of‐care testing. Methods We recruited healthy women aged 18‐44 planning a pregnancy. Participants used a home monitor to track LH and hCG levels for 12 menstrual cycles or until pregnancy was conceived. Pregnancy outcomes (viable, clinical miscarriage, or biochemical pregnancy loss) were recorded. Monitor data were analysed by a statistician blinded to pregnancy outcome. Results From 387 recruits, there were 290 pregnancies with known outcomes within study timeline. Adequate monitor data for analysis were available for 150 conceptive cycles. Overall spontaneous first‐trimester pregnancy loss rate was 30% with clinically recognised miscarriage rate of 17%. The difference to LH‐hCG interval median had wider spread for biochemical losses (0.5‐8.5 days) compared with clinical miscarriage (0‐5 days) and viable pregnancies (0‐6 days). Fixed effect hCG profile change distinguished between pregnancy outcomes from as early as day‐2 post‐hCG rise from baseline. Conclusions The risk of first‐trimester spontaneous pregnancy loss in our prospective cohort is comparable to studies utilising daily urinary hCG collection and laboratory assays. A wider LH‐hCG interval range is associated with biochemical pregnancy loss and may relate to late or early implantation. Although early hCG changes discriminate between pregnancies that will miscarry from viable pregnancies, this point‐of‐care testing model is not sufficiently developed to be predictive.

Embryo biosensing by uterine natural killer cells determines endometrial fate decisions at implantation

“…Based on sensitive urinary hCG measurements, several prospective observational studies reported miscarriage rates of approximately 30% in young women trying to conceive. [44][45][46][47] Most of these losses involve menstruation-like shedding of the endometrium 1-2 weeks after implantation and are, therefore, often not recognized clinically. The high attrition rate in the very early stages of pregnancy is widely attributed to embryonic aneuploidy, caused either by age-dependent meiotic errors in oocytes or age-independent erroneous mitotic divisions during preimplantation development.…”

Involvement of uterine natural killer cells in the natural selection of human embryos at implantation

“…Based on sensitive urinary hCG measurements, several prospective observational studies reported miscarriage rates of approximately 30% in young women trying to conceive. 41–44 Most of these losses involve menstruation-like shedding of the endometrium one to two weeks after implantation and are therefore often not recognised clinically. The high attrition rate in the very early stages of pregnancy is widely attributed to embryonic aneuploidy, caused either by age-dependent meiotic errors in oocytes or age-independent erroneous mitotic divisions during pre-implantation development.…”

Jointly modelling longitudinally measured urinary human chorionic gonadotrophin and early pregnancy outcomes

“…This analysis echoes research suggesting declines in hCG can be noted even prior to other symptoms presenting 20 . There is also potential for this monitoring to occur prior to conception, with a recent study finding that a lag between the luteal phase and hCG production can be indicative of a biochemical pregnancy, possibly due to early or delayed implantation 21 .…”

“…Tracking of hCG by pregnant women is practicable, as demonstrated by Foo et al who employed a fertility monitor that also provide semi-quantitative analysis of hCG levels on pregnancy tests that were used daily in women who conceived 21 . Retrospective analysis of the semi-quantitative data indicated that non-viable pregnancies had different hCG profiles to viable pregnancies.…”