Machine-Learning Prediction of Pregnancy Outcomes After Assisted Reproductive Treatments
Development and Validation of a Machine Learning Prognostic Model for Early Prediction of Pregnancy Outcomes Following Assisted Reproductive Treatment: A Retrospective and Prospective Cohort Study
The goal of this observational study is to develop and validate a machine-learning model to predict pregnancy outcomes in women with a positive pregnancy test following assisted reproductive treatment (ART), with the primary analysis focusing on in vitro fertilization (IVF) and frozen embryo transfer (FET). The study will also include an exploratory analysis of pregnancies following intrauterine insemination (IUI). The main questions addressed by the study are:
Can early blood levels of beta-human chorionic gonadotropin (beta-hCG) predict the likelihood of live birth in an IVF or FET cycle? Can early beta-hCG levels help identify pregnancies at increased risk of biochemical pregnancy or early pregnancy loss?
Participants will have clinical and treatment information, including beta-hCG measurements and pregnancy outcomes, collected from medical records or during prospective follow-up. No changes to participants' medical treatment will be made as part of the study.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
Infertility affects more than 15% of the global population, and ART are increasingly used to achieve pregnancy. The field continues to evolve rapidly with ongoing technological and clinical advances. Although these advances have improved ART, success rates continue to vary, contributing to significant psychological distress among patients due to uncertainty regarding outcomes.
The most intense stress typically occurs after the procedure, especially following a positive pregnancy test and before ultrasound confirmation. This period, which lasts at least 3-4 weeks, is characterized by considerable uncertainty, as neither patients nor healthcare providers have reliable tools to determine pregnancy viability, assess early development, or accurately predict pregnancy progression. An individualized assessment of the probability of live birth after a positive pregnancy test could provide clinically meaningful information during this period and potentially improve counseling and management of patient expectations.
Serum beta-hCG is one of the earliest measurable biomarkers following embryo implantation and has long been recognized as an important prognostic marker of early pregnancy outcome. Both the absolute concentration of beta-HCG and its subsequent rate of increase have been associated with pregnancy viability and live birth following embryo transfer.
Investigators plan to use a machine-learning system to collect and analyze retrospective clinical data. Beta-HCG values from this dataset were collected at very early stages of pregnancy (around aspiration days +14 and 16, and post-FET days 9 and 11).
Patients were advised to have blood drawn for beta-HCG measurement 14 days after oocyte aspiration or insemination, followed by a second measurement two days later. For FET, measurements were taken 9 days after blastocyst transfer (or the corresponding day for cleavage-stage embryos) and two days afterward. Due to scheduling constraints, such as weekends, actual measurements may have occurred one day earlier or later, or several days apart. The dataset included the exact dates of each blood draw, allowing precise calculation of the interval between measurements for analysis.
ART outcomes were primarily collected through direct patient reporting of events, including adverse pregnancy outcomes or live birth; for patients who did not report the outcomes, clinic staff conducted follow-up calls to ensure complete follow-up.
This study is an observational retrospective-prospective cohort study for development and validation of an AI (artificial intelligence) - based prognostic model predicting live birth after ART.
The retrospective phase will use existing clinical data from patients who underwent ART procedures at the BetaPlus Center between January 2017 and 31.12.2025.
The prospective phase will include consecutive patients undergoing ART after model development in both BetaPlus Center and Clinical University Hospital in Rijeka. These patients will be followed to assess pregnancy outcomes, enabling external validation of the model.
The study is observational in nature. No interventions, treatment modifications, or randomization will be performed as part of this research. Clinical management will follow standard operating procedures (SOP) independent of model predictions.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Kontakter og lokationer
Studiekontakt
Studiekontakt
- Navn: Romana Dmitrovic
- Telefonnummer: +385981983563
- E-mail: romana@betaplus.hr
Studiesteder
-
-
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Rijeka, Kroatien
- Rekruttering
- Clinical Hospital Center
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Kontakt:
- Neda Smiljan Severinski
- Telefonnummer: +385913644239
- E-mail: nedass@medri.uniri.hr
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Zagreb, Kroatien, 10000
- Rekruttering
- BetaPlus Center for Reproductive Medicine
-
Kontakt:
- Martina Kuzman
- Telefonnummer: +385993765735
- E-mail: martina@betaplus.hr
-
-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Participants will be women undergoing ART at the BetaPlus Center and, during the prospective validation phase, at the Clinical University Hospital in Rijeka, Croatia. The study population will include patients undergoing IVF/ICSI, FET, or IUI.
Beskrivelse
Inclusion Criteria:
- Women who underwent ART procedures (IUI, IVF/ICSI, or FET) using homologous oocytes.
- Availability of at least one positive early serum beta-HCG measurement after aspiration, FET, or insemination (beta-HCG >10 mIU/mL).
- Availability of the pregnancy outcome.
- Availability of relevant patient characteristics and clinical variables required for predictive modeling.
- For embryo-transfer cycles, availability of information on embryo developmental stage and number of embryos transferred where applicable.
- For the prospective validation cohort, written informed consent.
Exclusion Criteria
- Missing beta-HCG measurements critical for model input.
- Missing key demographic or clinical variables required for predictive modeling.
- Missing ART treatment protocol where required for the model.
- Missing pregnancy outcomes.
- Multiple pregnancy, hydatidiform mole, heterotopic pregnancy, and ectopic pregnancy will be excluded from the primary live-birth analysis but will be described separately and, where sample size permits, evaluated as secondary adverse pregnancy outcomes.
- Non-consent for prospective participation in validation.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: COHORT
- Tidsperspektiver: OTHER
Antal grupper/kohorter
Kohorter og interventioner
Gruppe / kohorteGruppe / kohorte |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
ART pregnancies with positive beta-hCG
Patients with a positive serum beta-hCG measurement following ART, including IVF, FET, and IUI. Participants will be followed to assess pregnancy outcomes, including live birth, biochemical pregnancy, and early pregnancy loss. |
A machine-learning prognostic model using early serum beta-hCG measurements and patient, embryo, and treatment characteristics to predict live birth and early adverse pregnancy outcomes following assisted reproductive treatment. |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Live birth following ART
Tidsramme: From positive pregnancy test until delivery.
|
Delivery of a live infant at ≥24 weeks of gestation. |
From positive pregnancy test until delivery.
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Biochemical pregnancy following ART
Tidsramme: From the first positive serum beta-hCG measurement until biochemical pregnancy resolution.
|
A pregnancy characterized by a positive serum beta-hCG test followed by bleeding or pregnancy loss without ultrasound confirmation of a clinical pregnancy. |
From the first positive serum beta-hCG measurement until biochemical pregnancy resolution.
|
|
Early Pregnancy Loss following ART
Tidsramme: From clinical pregnancy confirmation until 12 weeks of gestation.
|
Pregnancy loss occurring before 12 weeks of gestation, excluding biochemical pregnancy, ectopic pregnancy, heterotopic pregnancy, and hydatidiform mole. |
From clinical pregnancy confirmation until 12 weeks of gestation.
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Samarbejdspartnere
Samarbejdspartnere
Efterforskere
Efterforskere
- Ledende efterforsker: Romana Dmitrovic, BetaPlus Center for Reproductive Medicine
Publikationer og nyttige links
Generelle publikationer
- Clarke EA, Jones C, Reckhow J, Flannagan K, Shaari D, Baird M, Lee JA, Sekhon L, Copperman AB, Romanski PA. Prognostic utility of serum beta human chorionic gonadotropin level following single euploid embryo transfer for live birth. Fertil Steril. 2026 Aug;126(2):371-378. doi: 10.1016/j.fertnstert.2026.04.025. Epub 2026 May 4.
- Papageorgiou TC, Leondires MP, Miller BT, Chang AS, Armstrong AB, Scott LA, Segars JH. Human chorionic gonadotropin levels after blastocyst transfer are highly predictive of pregnancy outcome. Fertil Steril. 2001 Nov;76(5):981-7. doi: 10.1016/s0015-0282(01)02840-0.
- Mourad A, Antaki R, Rowen M, Levesque E, Lapensee L. The POPI-Plus tool: prediction model of outcome of pregnancy in in vitro fertilization from a large retrospective cohort. Fertil Steril. 2024 Mar;121(3):489-496. doi: 10.1016/j.fertnstert.2023.11.035. Epub 2023 Dec 1.
- Kidera N, Ishikawa T, Kawamura T, Miyasaka N. Serum human chorionic gonadotropin can predict live birth 7 days after frozen-thawed blastocyst transfer. F S Rep. 2025 Oct 23;6(4):455-461. doi: 10.1016/j.xfre.2025.10.002. eCollection 2025 Dec.
- Kalafat E, Ata B, Del Gallego R, Freedman A, Hoyos LR, Elkhatib I, Miller KA, Fatemi H, Lawrenz B. Predicting live birth following single euploid frozen-embryo transfer via beta-hCG dynamics: iHOPE prognostic model with external validation. Ultrasound Obstet Gynecol. 2026 Jun;67(6):824-835. doi: 10.1002/uog.70238. Epub 2026 May 24.
- Schmidt LL, Asch RH, Frederick JL, Rojas FJ, Stone SC, Balmaceda JP. The predictive value of a single beta human chorionic gonadotropin in pregnancies achieved by assisted reproductive technology. Fertil Steril. 1994 Aug;62(2):333-8. doi: 10.1016/s0015-0282(16)56887-3.
- Hughes LM, Schuler A, Sharmuk M, Schauer JM, Pavone ME, Bernardi LA. Early beta-hCG levels predict live birth after single embryo transfer. J Assist Reprod Genet. 2022 Oct;39(10):2355-2364. doi: 10.1007/s10815-022-02606-w. Epub 2022 Sep 8.
- Trautner PS, Oppelt P, Resch S, Enzelsberger SH, Ebner T, Shebl OJ. Single day 14 serum hCG values allow prediction of viable pregnancy and are significantly higher in frozen as compared to fresh single blastocyst transfer. J Assist Reprod Genet. 2024 Aug;41(8):2193-2200. doi: 10.1007/s10815-024-03164-z. Epub 2024 Jun 13.
- Al Mamari N, Al Zawawi N, Khayat S, Badeghiesh A, Son WY, Dahan MH. Revisiting serum beta-hCG cut-off levels and pregnancy outcomes using single embryo transfer. J Assist Reprod Genet. 2019 Nov;36(11):2307-2313. doi: 10.1007/s10815-019-01583-x. Epub 2019 Oct 12.
- Sarret Y, Reano A, Nicolas JF, Su H, Thivolet J. Bullous pemphigoid and cicatricial pemphigoid: immunoblotting detection of involved autoantigens. Autoimmunity. 1989;2(2):145-53. doi: 10.3109/08916938909019951.
- Hobeika E, Singh S, Malik S, Knochenhauer ES, Traub ML. Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort. J Assist Reprod Genet. 2017 Oct;34(10):1333-1340. doi: 10.1007/s10815-017-0987-2. Epub 2017 Jun 21.
- Kathiresan AS, Cruz-Almeida Y, Barrionuevo MJ, Maxson WS, Hoffman DI, Weitzman VN, Christie DR, Manko GF, Ory SJ. Prognostic value of beta-human chorionic gonadotropin is dependent on day of embryo transfer during in vitro fertilization. Fertil Steril. 2011 Dec;96(6):1362-6. doi: 10.1016/j.fertnstert.2011.09.042. Epub 2011 Nov 1.
- Oron G, Shavit T, Esh-Broder E, Weon-Young S, Tulandi T, Holzer H. Predictive value of serum HCG concentrations in pregnancies achieved after single fresh or vitrified-warmed blastocyst transfer. Reprod Biomed Online. 2017 Sep;35(3):272-278. doi: 10.1016/j.rbmo.2017.05.011. Epub 2017 May 30.
- Oron G, Esh-Broder E, Son WY, Holzer H, Tulandi T. Predictive value of maternal serum human chorionic gonadotropin levels in pregnancies achieved by in vitro fertilization with single cleavage and single blastocyst embryo transfers. Fertil Steril. 2015 Jun;103(6):1526-31.e1-2. doi: 10.1016/j.fertnstert.2015.02.028. Epub 2015 Apr 22.
- Ozer G. Initial beta-hCG levels and 2-day-later increase rates effectively predict pregnancy outcomes in single blastocyst transfer in frozen-thawed or fresh cycles: A retrospective cohort study. Medicine (Baltimore). 2023 Oct 20;102(42):e35605. doi: 10.1097/MD.0000000000035605.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- PK 1.1.12.0074
- PK 1.1.12.0074 (Andet bevillings-/finansieringsnummer: HAMAG BICRO)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
De-identified individual participant data underlying the results of this study will be made available upon reasonable request. The shared dataset will include the clinical and treatment variables necessary to reproduce or further investigate the study findings, including relevant beta-hCG measurements, timing of measurements, ART treatment characteristics, and pregnancy outcomes.
Data will not include names, contact information, medical record numbers, or other directly identifying information.
IPD-delingstidsramme
After publication and for 5 years thereafter
IPD-delingsadgangskriterier
Data will be available to qualified researchers, subject to applicable ethical, legal, and institutional requirements
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
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