{"id":17741,"date":"2017-12-21T11:00:03","date_gmt":"2017-12-21T11:00:03","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=17741"},"modified":"2018-08-24T05:23:27","modified_gmt":"2018-08-24T05:23:27","slug":"maternal-beta-hcg-levels-day-12-after-embryo-transfer-to-predict-pregnancy-outcome-in-in-vitro-fertilization-clinic-prima-medika-denpasar-bali-indonesia","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol10no4\/maternal-beta-hcg-levels-day-12-after-embryo-transfer-to-predict-pregnancy-outcome-in-in-vitro-fertilization-clinic-prima-medika-denpasar-bali-indonesia\/","title":{"rendered":"Maternal Beta Hcg Levels Day 12 After Embryo Transfer to Predict Pregnancy Outcome in In-Vitro Fertilization Clinic Prima Medika, Denpasar Bali Indonesia"},"content":{"rendered":"<p><strong>Introduction<\/strong><\/p>\n<p>The ability to predict the occurrence of pregnancy in the Assisted Reproductive Technology (ART) program is desirable both for the clinician and the patient. Some serum markers have been studied in relation to pregnancy, such as \u03b2-subunits from human chorionic gonadotropin (\u03b2-hCG), estradiol, progesterone, cancer antigen-125 (Ca-125), activin, and inhibin. \u03b2-hCG has proven to be the most predictive factor. Pregnancy obtained through IVF with or without ICSI has a high risk of obstetric and perinatal complications compared to spontaneous pregnancy.<sup>1,2,3 <\/sup>Ultrasound scanning is part of what is routinely done after embryo transfer, but the gestational sac can only be seen clearly during the third week after embryo transfer.<sup>4,5<\/sup><\/p>\n<p>The success of embryo implantation, with invasion and proliferation of trophoblast cells, depends on endometrial receptivity. Estradiol (E2) is formed in the follicle , and the high number of pre-ovulatory follicles shows high E2 levels. Further affects the final oocyte maturation process with hCG in invitro fertilization (IVF),\u00a0 the suprafisiological formation of \u00a0E2 and progesterone concentrations in the initial luteal phase, including the time of implantation. The high number of oocytes obtained during oocyte retrieval can lead to subsequent embryo-endometrial asynchrony affecting the embryo implantation process, resulting in less optimal trophoblast proliferation and low \u03b2-hCG levels.<sup>6<\/sup><\/p>\n<p><strong>M<\/strong><strong>a<\/strong><strong>t<\/strong><strong>erials <\/strong><strong>a<\/strong><strong>nd Methods<\/strong><\/p>\n<p>In vitro fertilization clinic, Prima Medika Hospital Denpasar in January &#8211; Desember 2015, there are 138 participants who follow In-vitro Fertilization (IVF) program, with 123 participants who can follow up in the Ovum Pick Up (OPU) stage. Fifty-seven participants tested positive for biochemical pregnancy (46.3%) and 42 participants tested positive for clinical pregnancy (34.1%). The inclusion criteria is patient medical record data in Medical Record Unit of Prima Medika Hospital Denpasar, with positive biochemical pregnancy result after transfer of at least two embryo 8 cells. Levels of serum \u00df-hCG were measured on the twelfth day after embryo transfer, at In vitro fertilization clinic, Prima Medika Hospital Denpasar, using immunoassay electroiluminesens method, measuring \u00df-hCG levels to a minimum of &lt;2.00 mIU\/ml. Participants who tested positive for biochemical pregnancy were \u00df-hCG&gt; 10 mIU\/mL. Of the 57 participants who had positive \u00df-hCG levels, followed by 12 weeks&#8217; gestation, they were grouped into two major groups: viable pregnancies (ongoing pregnancy) and non-viable pregnancies (abortion, ectopic pregnancy, and biochemical pregnancy). Using an independent T-Test can detect the average difference in \u00df-hCG levels between biochemical pregnancies, and abortion. The ANOVA (analysis of variance) test can determine the difference in mean \u00df-hCG levels between single pregnancy, twin pregnancy, and multiple pregnancies, with 95% confidence intervals.<sup>7<\/sup> As additional analysis, adjusted body mass index (BMI), maternal age and infertile duration. Statistical analysis was performed with SPSS IBM Statistical Package version 17 for Windows with p &lt;0.05 being significant.<\/p>\n<p><strong>Results and Discussion<\/strong><\/p>\n<p>The mean \u03b2-hCG levels on day 12 after embryo transfer based on maternal age, body mass index and infertile duration. The mean \u00df-hCG concentrations based on maternal age (23-33 years vs 34-45 years) were obtained (357.9 + 276.7 vs 269.5 \u00b1 244.4 mIU\/mL), where the differences in both groups did not differ significantly statistically (p = 0.206). Based on body mass index (BMI), the sample with IMT 18-24 kg\/m<sup>2<\/sup> was 349.1 \u00b1 290.8 mIU\/mL, while sample with IMT&gt; 24 kg\/m<sup>2<\/sup> was 281.0 \u00b1 232.9 mIU\/mL. Differences in both BMI groups showed no statistically significant (p = 0.335). Infertile duration between 1-10 years, the average \u00df-hCG concentration was 324.9 \u00b1 268.2 mIU\/mL. The mean \u03b2-hCG concentration in infertile 11-20 years was 176.5 \u00b1 121.8 mIU\/mL, where the difference between the two groups did not differ significantly (p = 0.086) (table 1). Sekhonm <em>et al.,<\/em> on observation of 458 patients who became pregnant after a single frozen embryo transfer (FET) transfer also found that maternal age factors did not differ significantly statistically.<sup>8<\/sup> Similarly, in embryo or blastocyst transfer, the \u03b2-hCG concentration in days 14 and 16 after OPU have no significant correlation with maternal age.<sup>9<\/sup><\/p>\n<p><strong>Table 1: Characteristics of Research Samples Based on Maternal-\u03b2-hCG Levels<\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"156\"><strong>Variables\u00a0<\/strong><\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"72\"><strong>Category<\/strong><\/td>\n<td style=\"text-align: center;\" colspan=\"3\" width=\"318\"><strong>Levels of \u00df-hCG Maternal (mIU \/ mL)<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"108\"><strong>Mean<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"132\"><strong>Standard Deviation<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"78\"><strong>P<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"156\">Maternal Age (Years)<\/td>\n<td style=\"text-align: center;\" width=\"72\">23 \u2013 33<\/td>\n<td style=\"text-align: center;\" width=\"108\">357.9<\/td>\n<td style=\"text-align: center;\" width=\"132\">276.7<\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"78\">0.206<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"72\">34 \u2013 45<\/td>\n<td style=\"text-align: center;\" width=\"108\">269.5<\/td>\n<td style=\"text-align: center;\" width=\"132\">244.4<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"156\">Body Mass Index (BMI) \u00a0(kg\/m<sup>2<\/sup>)<\/td>\n<td style=\"text-align: center;\" width=\"72\">18 \u2013 24<\/td>\n<td style=\"text-align: center;\" width=\"108\">349.1<\/td>\n<td style=\"text-align: center;\" width=\"132\">290.8<\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"78\">0.335<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"72\">&gt; 24<\/td>\n<td style=\"text-align: center;\" width=\"108\">281.0<\/td>\n<td style=\"text-align: center;\" width=\"132\">232.9<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"156\">Infertile duration<\/p>\n<p>(Years)<\/td>\n<td style=\"text-align: center;\" width=\"72\">1 \u2013 10<\/td>\n<td style=\"text-align: center;\" width=\"108\">324.9<\/td>\n<td style=\"text-align: center;\" width=\"132\">268.2<\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"78\">0.086<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"72\">11 \u2013 20<\/td>\n<td style=\"text-align: center;\" width=\"108\">176.5<\/td>\n<td style=\"text-align: center;\" width=\"132\">121.8<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>The mean maternal \u00df-hCG concentrations in the viable pregnancy were higher than non-viable pregnancies (419.7 vs 44.8 mIU\/mL, P = 0.000). In non-viable pregnancies, for mean \u03b2-hCG levels in biochemical pregnancy was lower than abortion (24.3 vs 165.2 mIU\/mL) but not statistically significant (P = 0.495). Wang et al., in 212 IVF cycles received \u00df-hCG 10 days after OPU differed significantly in both viable and non-viable pregnancies, as well as in single pregnancy and multiple pregnancy.<sup>10<\/sup> Similarly, Reljic et al. found significantly different levels of \u00df-hCG in both viable and non-viable pregnancies in the group of fresh embryo transfer and frozen embryo transfer examined on day 13 after embryo transfer.<sup>11<\/sup> The mean \u00df-hCG concentrations in single pregnancies, twin pregnancies, and multiple pregnancies suggest a significant difference, as shown in Table 2.<\/p>\n<p>In a viable pregnancy, the mean \u03b2-hCG concentrations in single pregnancies is smaller with twin pregnancies (gemelli) and is statistically significant (p = 0.008). The mean \u03b2-hCG levels of multiple pregnancies were greater than that of single pregnancies, which were statistically significant (p = 0.004). Meanwhile, the mean \u00df-hCG concentrations in multiple pregnancies and twin pregnancies (gemelli) were different but not statistically (p = 0.283), as in Table 3.<\/p>\n<p><strong>Table 2: Mean of Maternal \u03b2-hCG Based Maternal Ratio Viability<\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" rowspan=\"6\" width=\"90\"><strong>Category<\/strong><\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"186\"><strong>Variables\u00a0<\/strong><\/td>\n<td style=\"text-align: center;\" colspan=\"3\" width=\"267\"><strong>Levels of \u00df-hCG Maternal (mIU \/ mL)<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"64\"><strong>Mean<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"122\"><strong>Standard Deviation<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"81\"><strong>P<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">Non-viable<\/td>\n<td style=\"text-align: center;\" width=\"64\">44.8<\/td>\n<td style=\"text-align: center;\" width=\"122\">72.9<\/td>\n<td style=\"text-align: center;\" width=\"81\">0.000<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">Biochemical Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"64\">24.3<\/td>\n<td style=\"text-align: center;\" width=\"122\">22.5<\/td>\n<td style=\"text-align: center;\" width=\"81\">0.495<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">Ectopic Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"64\">70.5<\/td>\n<td style=\"text-align: center;\" width=\"122\">&#8211;<\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"81\"><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">Abortion<\/td>\n<td style=\"text-align: center;\" width=\"64\">165.2<\/td>\n<td style=\"text-align: center;\" width=\"122\">196.5<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" rowspan=\"4\" width=\"90\"><strong>Category\u00a0<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"186\">Ongoing pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"64\">419.7<\/td>\n<td style=\"text-align: center;\" width=\"122\">232.9<\/td>\n<td style=\"text-align: center;\" width=\"81\">0.000<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">Single Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"64\">272.7<\/td>\n<td style=\"text-align: center;\" width=\"122\">155.0<\/td>\n<td style=\"text-align: center;\" width=\"81\">0.000<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">Twins Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"64\">497.9<\/td>\n<td style=\"text-align: center;\" width=\"122\">192.7<\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"81\"><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"186\">Multiple Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"64\">683.3<\/td>\n<td style=\"text-align: center;\" width=\"122\">194.4<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>Sing N, <em>et al.<\/em> on observation of median \u00df-hCG levels on day 14 after transfer embryo, found significant differences in median \u00df-hCG concentrations in viable pregnancies (625 IU\/L) and non-viabel (174 IU\/L), while median \u03b2-hCG levels singleton pregnancies (502 IU\/L), twins (1093 IU\/L) and triplets (2160 IU\/L) were statistically significant.<sup>12<\/sup><\/p>\n<p><strong>Table 3: Differences in Maternal-\u03b2-hCG Levels by Number of Fetuses<\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"90\"><strong>Variables<\/strong><\/td>\n<td style=\"text-align: center;\" rowspan=\"2\" width=\"252\"><strong>Category\u00a0<\/strong><\/td>\n<td style=\"text-align: center;\" colspan=\"2\" width=\"201\"><strong>Levels of \u00df-hCG Maternal (mIU\/mL)<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"126\"><strong>Mean Diff.<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"75\"><strong>P<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" rowspan=\"6\" width=\"90\"><strong>Viable pregnancy<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"252\">Single Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"126\">410.56<\/td>\n<td style=\"text-align: center;\" width=\"75\">0.004<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"252\">Multiple Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"126\"><\/td>\n<td style=\"text-align: center;\" width=\"75\"><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"252\">Twin Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"126\">185.44<\/td>\n<td style=\"text-align: center;\" width=\"75\">0.283<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"252\">Multiple Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"126\"><\/td>\n<td style=\"text-align: center;\" width=\"75\"><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"252\">Single Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"126\">225.12<\/td>\n<td style=\"text-align: center;\" width=\"75\">0.008<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"252\">Twin Pregnancy<\/td>\n<td style=\"text-align: center;\" width=\"126\"><\/td>\n<td style=\"text-align: center;\" width=\"75\"><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p><strong>Conclusions and Suggestions<\/strong><\/p>\n<p>In this study there was a difference in mean \u00df-hCG concentrations in viable pregnancies and non-viable pregnancies, with greater viable pregnancies. In single pregnancies, twin pregnancies and multiple pregnancies, there is a statistically significant difference.<\/p>\n<p>In this study it was found that maternal \u00df-hCG levels in very early pregnancy showed a significant difference based on viability. This finding has an effect on the interpretation of \u00df-hCG levels after the ART program<\/p>\n<p><strong>Acknowledgement<\/strong><\/p>\n<p>The researcher would like to thank dr. H.M. Ilyas Angsar, SpOG (K), Head of In-vitro Fertilization Clinic, Prima Medika Hospital, Denpasar<\/p>\n<p><strong>References<\/strong><\/p>\n<ol>\n<li>Chen X, Huang Y, Guo P.P, <em>et al<\/em>. The association between serum \u00df- hCG on day 24 of pregnancy and ongoing pregnancy in frozen embryo transfer cycles.<em> International Journal of Gynecology and Obstetrics.<\/em>\u00a0<em>Source Science Direct<\/em>. 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Dasar-dasar Metodologi Penelitian Klinis. Jakarta: CV Sagung Seto. 2008;279-301.<\/li>\n<li>Sekhonm L, Rodriguez-Purata J, Aharon D, <em>et al<\/em>. Interpreting early HCG dynamics in the era of the thawed euploid single embryo transfer: how important is doubling? <em>Fertility and Sterility<\/em>. 2016;106(3):e341-e342.<br \/>\n<a href=\"https:\/\/doi.org\/10.1016\/j.fertnstert.2016.07.967\" target=\"_blank\">CrossRef<\/a><\/li>\n<li>McCoy W, Nakajima S.T, Bohler Jr H.C.\u00a0 Age and a single day-14 \u03b2-HCG can predict ongoing pregnancy following IVF. <em>Reproductive Bio.Medicine.<\/em> 2009;19(1):114-120.<br \/>\n<a href=\"https:\/\/doi.org\/10.1016\/S1472-6483(10)60054-5\" target=\"_blank\">CrossRef<\/a><\/li>\n<li>Wang Q, Zhang R, Jia M, <em>et al<\/em>. 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Vlaisavljevi\u0107 Human chorionic gonadotropin levels are equally predictive for pregnancy outcome after fresh and vitrified-warmed blastocyst transfer. <em>\u00a0Assisted Reproduction and Genetics.<\/em> 2013; 30(11):1459\u20131463.<br \/>\n<a href=\"https:\/\/doi.org\/10.1007\/s10815-013-0099-6\" target=\"_blank\">CrossRef<\/a><\/li>\n<li>Singh N, Begum A.A, Malhotra N, <em>et al. <\/em>Role of early serum beta human chorionic gonadotropin measurement in predicting multiple pregnancy and pregnancy wastage in an in vitro ET fertilization cycle. <em>Human Reproductive Sciences.<\/em> 2013;6(3):213-218.<br \/>\n<a href=\"https:\/\/doi.org\/10.4103\/0974-1208.121425\" target=\"_blank\">CrossRef<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>Introduction The ability to predict the occurrence of pregnancy in  [&#8230;]<\/p>\n","protected":false},"author":9,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[53],"tags":[],"class_list":["post-17741","post","type-post","status-publish","format-standard","hentry","category-vol10no4"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/17741","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/9"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=17741"}],"version-history":[{"count":12,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/17741\/revisions"}],"predecessor-version":[{"id":21985,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/17741\/revisions\/21985"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=17741"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=17741"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=17741"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}