Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle.

Infertility, Female Clinical Trial

Official title:

Descriptive Analysis of Serum Immunological Markers During an Euploid Frozen Embryo Transfer in a Natural Cycle (NC).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05473273
• Other study ID #: 2206-ABU-004-LMM
• Status: Recruiting
• Start date: April 24, 2023
• Est. completion date: January 30, 2024

Study information

• Verified date: July 2023
• Source: ART Fertility Clinics LLC
• Contact: BARBARA LAWRENZ, PhD
• Phone: 97126528000
• Email: barbara.lawrenz[@]artfertilityclinics.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To describe the peripheral serum levels of the anti-inflammatory cytokines IL-4 (Interleukin-4), IL-10 (Interleukin-10), TGF-ß1 (Transforming Growth Factor beta1), the pro-inflammatory cytokines IL-17 (Interleukin-17), IFγ (Interferon Gamma) and the immune mediator PIBF (Progesterone-Induced Blocking Factor) along a single frozen euploid blastocyst transfer in a natural cycle (NC) or Hormone Replacement Therapy (HRT).

Description:

This a prospective, observational study including 40 infertile patients undergoing a "single embryo transfer" (SET). Blood samples will be drawn for Progesterone-Induced Blocking Factor (PIBF), interleukin 17 (IL-17), Interferon Gamma (IFγ), Interleukin 10 (IL-10), Interleukin 4 (IL-4) and Transforming Growth Factor beta 1 (TGF-ß1) measurement on the day of ovulation in the natural cycle (NC) or first day of progesterone in the Hormone Replacement Therapy (HRT) protocol, on the day of embryo transfer (ET) and 3 and 10 days later, coinciding with the early and late embryo invasion stages respectively. In case of pregnancy, an additional blood test for PIBF, IL-17, IFγ, IL-10, IL-4, TGF-ß1 and ßHCG (Beta-Human Chorionic Gonadotropin) will be performed at 5 weeks +/- 3 days. The study will be performed at ART Fertility Clinics and the estimated completion time will be 12 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 30, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Women aged 18 years to 40 years
• Having at least one good quality (grade A or B for inner mass cell and trophectoderm) day 5 or 6 chromosomally normal cryopreserved blastocyst available for transfer
• Single embryo transfer in a natural cycle (NC) or an Hormone Replacement Therapy (HRT) protocol
• Fresh ejaculate used for fertilization

Exclusion Criteria:

• Body mass index lower than 18.5 or equal or higher than 29 kg/m2
• Endometriosis or adenomyosis suspected by medical history (dysmenorrhea, dyspareunia, heavy or prolonged menstrual bleeding (> 8 days), chronic pelvic pain, catamenial rectal or bladder symptoms) or diagnosed by imaging (magnetic resonance imaging or ultrasonography)
• Uterine abnormalities
• Hydrosalpinx
• Insulin resistance or diabetes mellitus diagnosed by HbA1c 5.7 %
• Antiphospholipid syndrome
• Polycystic ovarian syndrome according to Rotterdam criteria: presence of at least two of the following: irregular cycles (< 21 or > 35 days or < 8 cycles a year), biochemical or clinical hyperandrogenism, ovarian ultrasound morphology (> 20 follicles per ovary on transvaginal scan) or Anti-mullerian hormone > 5,98 ng/ml
• History of recurrent miscarriage, defined as the loss of 2 or more pregnancies according to ESHRE guidelines
• History of implantation failure, considered as the lack of pregnancy after the transfer of 2 good-quality (grade A or B for inner mass cell and trophectoderm (29)) euploid embryos
• History or suspicion of Asherman syndrome
• Autoimmune disease
• Couple first degree consanguineous

Related Conditions & MeSH terms

• Infertility
• Infertility, Female

Intervention

Drug:
• Endometrin 100Mg Vaginal Insert
Endometrin will start once endometrial thickness is equal or higher to 7 mm with a trilaminar appearance, after at least 10 days and always less than 16 days of estradiol administration. First day of supplementation a dose of 100mg will be administered at of at 1.pm and 9 pm. From the second day and onwards administration will be increased to three times daily, at 6 am, 2 pm and 10 pm
• Estradiol Valerate
Estradiol valerate dose will be reduced to 4mg daily at 7 pm during the first two days of vaginal natural micronized progesterone supplementation and increased afterwards to 6 mg daily (2 mg at 10 am and 4 mg at 7 pm).

Locations

Country	Name	City	State
United Arab Emirates	ART Fertility Clinics LLC	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
ART Fertility Clinics LLC

Country where clinical trial is conducted

United Arab Emirates, 

References & Publications (33)

Abdala A, Elkhatib I, Bayram A, Arnanz A, El-Damen A, Melado L, Lawrenz B, Fatemi HM, De Munck N. Day 5 vs day 6 single euploid blastocyst frozen embryo transfers: which variables do have an impact on the clinical pregnancy rates? J Assist Reprod Genet. 2022 Feb;39(2):379-388. doi: 10.1007/s10815-021-02380-1. Epub 2022 Jan 22. — View Citation

AbdulHussain G, Azizieh F, Makhseed M, Raghupathy R. Effects of Progesterone, Dydrogesterone and Estrogen on the Production of Th1/Th2/Th17 Cytokines by Lymphocytes from Women with Recurrent Spontaneous Miscarriage. J Reprod Immunol. 2020 Aug;140:103132. doi: 10.1016/j.jri.2020.103132. Epub 2020 Apr 17. — View Citation

Bourdon M, Santulli P, Jeljeli M, Vannuccini S, Marcellin L, Doridot L, Petraglia F, Batteux F, Chapron C. Immunological changes associated with adenomyosis: a systematic review. Hum Reprod Update. 2021 Jan 4;27(1):108-129. doi: 10.1093/humupd/dmaa038. — View Citation

Calzada M, Lopez N, Noguera JA, Mendiola J, Hernandez AI, Corbalan S, Sanchez M, Torres AM. AMH in combination with SHBG for the diagnosis of polycystic ovary syndrome. J Obstet Gynaecol. 2019 Nov;39(8):1130-1136. doi: 10.1080/01443615.2019.1587604. Epub 2019 Jun 17. — View Citation

Chaouat G, Menu E, Clark DA, Dy M, Minkowski M, Wegmann TG. Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy. J Reprod Fertil. 1990 Jul;89(2):447-58. doi: 10.1530/jrf.0.0890447. — View Citation

Chen JZ, Sheehan PM, Brennecke SP, Keogh RJ. Vessel remodelling, pregnancy hormones and extravillous trophoblast function. Mol Cell Endocrinol. 2012 Feb 26;349(2):138-44. doi: 10.1016/j.mce.2011.10.014. Epub 2011 Oct 25. — View Citation

Conrad KP, Baker VL. Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies. Am J Physiol Regul Integr Comp Physiol. 2013 Jan 15;304(2):R69-72. doi: 10.1152/ajpregu.00239.2012. Epub 2012 Oct 24. — View Citation

DeJong CS, Maurice NJ, McCartney SA, Prlic M. Human Tissue-Resident Memory T Cells in the Maternal-Fetal Interface. Lost Soldiers or Special Forces? Cells. 2020 Dec 16;9(12):2699. doi: 10.3390/cells9122699. — View Citation

Diaz-Hernandez I, Alecsandru D, Garcia-Velasco JA, Dominguez F. Uterine natural killer cells: from foe to friend in reproduction. Hum Reprod Update. 2021 Jun 22;27(4):720-746. doi: 10.1093/humupd/dmaa062. — View Citation

Fatemi HM, Kyrou D, Bourgain C, Van den Abbeel E, Griesinger G, Devroey P. Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle. Fertil Steril. 2010 Nov;94(6):2054-8. doi: 10.1016/j.fertnstert.2009.11.036. Epub 2010 Jan 25. — View Citation

Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, Osteen K, Taylor RN, Lessey BA, Giudice LC. Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002 Jun;143(6):2119-38. doi: 10.1210/endo.143.6.8885. — View Citation

Keskin DB, Allan DS, Rybalov B, Andzelm MM, Stern JN, Kopcow HD, Koopman LA, Strominger JL. TGFbeta promotes conversion of CD16+ peripheral blood NK cells into CD16- NK cells with similarities to decidual NK cells. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3378-83. doi: 10.1073/pnas.0611098104. Epub 2007 Feb 20. — View Citation

Labarta E, Mariani G, Paolelli S, Rodriguez-Varela C, Vidal C, Giles J, Bellver J, Cruz F, Marzal A, Celada P, Olmo I, Alama P, Remohi J, Bosch E. Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone. Hum Reprod. 2021 Feb 18;36(3):683-692. doi: 10.1093/humrep/deaa322. — View Citation

Labarta E, Sebastian-Leon P, Devesa-Peiro A, Celada P, Vidal C, Giles J, Rodriguez-Varela C, Bosch E, Diaz-Gimeno P. Analysis of serum and endometrial progesterone in determining endometrial receptivity. Hum Reprod. 2021 Oct 18;36(11):2861-2870. doi: 10.1093/humrep/deab184. — View Citation

Lash GE, Robson SC, Bulmer JN. Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua. Placenta. 2010 Mar;31 Suppl:S87-92. doi: 10.1016/j.placenta.2009.12.022. Epub 2010 Jan 12. — View Citation

Liu Y, Gao S, Zhao Y, Wang H, Pan Q, Shao Q. Decidual Natural Killer Cells: A Good Nanny at the Maternal-Fetal Interface During Early Pregnancy. Front Immunol. 2021 May 12;12:663660. doi: 10.3389/fimmu.2021.663660. eCollection 2021. — View Citation

Lucas ES, Vrljicak P, Muter J, Diniz-da-Costa MM, Brighton PJ, Kong CS, Lipecki J, Fishwick KJ, Odendaal J, Ewington LJ, Quenby S, Ott S, Brosens JJ. Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Commun Biol. 2020 Jan 21;3(1):37. doi: 10.1038/s42003-020-0763-1. — View Citation

Matalka KZ. The effect of estradiol, but not progesterone, on the production of cytokines in stimulated whole blood, is concentration-dependent. Neuro Endocrinol Lett. 2003 Jun-Aug;24(3-4):185-91. — View Citation

Mor G, Aldo P, Alvero AB. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol. 2017 Aug;17(8):469-482. doi: 10.1038/nri.2017.64. Epub 2017 Jun 19. — View Citation

Munro MG, Critchley HOD, Fraser IS; FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet. 2018 Dec;143(3):393-408. doi: 10.1002/ijgo.12666. Epub 2018 Oct 10. Erratum In: Int J Gynaecol Obstet. 2019 Feb;144(2):237. — View Citation

Murphy SP, Tayade C, Ashkar AA, Hatta K, Zhang J, Croy BA. Interferon gamma in successful pregnancies. Biol Reprod. 2009 May;80(5):848-59. doi: 10.1095/biolreprod.108.073353. Epub 2009 Jan 21. — View Citation

Piccinni MP, Raghupathy R, Saito S, Szekeres-Bartho J. Cytokines, Hormones and Cellular Regulatory Mechanisms Favoring Successful Reproduction. Front Immunol. 2021 Jul 28;12:717808. doi: 10.3389/fimmu.2021.717808. eCollection 2021. — View Citation

Raghupathy R, Szekeres-Bartho J. Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy. Int J Mol Sci. 2022 Jan 25;23(3):1333. doi: 10.3390/ijms23031333. — View Citation

Robertson SA, Moldenhauer LM. Immunological determinants of implantation success. Int J Dev Biol. 2014;58(2-4):205-17. doi: 10.1387/ijdb.140096sr. — View Citation

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004. — View Citation

Salem ML. Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production. Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):97-104. doi: 10.2174/1568010043483944. — View Citation

Szekeres-Bartho J. The Role of Progesterone in Feto-Maternal Immunological Cross Talk. Med Princ Pract. 2018;27(4):301-307. doi: 10.1159/000491576. Epub 2018 Jun 27. — View Citation

Wang W, Sung N, Gilman-Sachs A, Kwak-Kim J. T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells. Front Immunol. 2020 Aug 18;11:2025. doi: 10.3389/fimmu.2020.02025. eCollection 2020. — View Citation

Wu HX, Jin LP, Xu B, Liang SS, Li DJ. Decidual stromal cells recruit Th17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17. Cell Mol Immunol. 2014 May;11(3):253-62. doi: 10.1038/cmi.2013.67. Epub 2014 Mar 17. — View Citation

Xu WM, Xiao ZN, Wang XB, Huang Y. IL-17 Induces Fetal Loss in a CBA/JxBALB/c Mouse Model, and an Anti-IL-17 Antibody Prevents Fetal Loss in a CBA/JxDBA/2 Mouse Model. Am J Reprod Immunol. 2016 Jan;75(1):51-8. doi: 10.1111/aji.12437. Epub 2015 Oct 17. — View Citation

Yang D, Dai F, Yuan M, Zheng Y, Liu S, Deng Z, Tan W, Chen L, Zhang Q, Zhao X, Cheng Y. Role of Transforming Growth Factor-beta1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy. Front Immunol. 2021 Aug 31;12:689181. doi: 10.3389/fimmu.2021.689181. eCollection 2021. — View Citation

Zhang X, Wei H. Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications. Front Immunol. 2021 Aug 26;12:728291. doi: 10.3389/fimmu.2021.728291. eCollection 2021. — View Citation

Zhao Y, Zhang T, Guo X, Wong CK, Chen X, Chan YL, Wang CC, Laird S, Li TC. Successful implantation is associated with a transient increase in serum pro-inflammatory cytokine profile followed by a switch to anti-inflammatory cytokine profile prior to confirmation of pregnancy. Fertil Steril. 2021 Apr;115(4):1044-1053. doi: 10.1016/j.fertnstert.2020.10.031. Epub 2020 Nov 30. — View Citation

* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood levels of IL-4 (Interleukin 4) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of IL-4 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of IL-10 (Interleukin 10) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of IL-10 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of IL-17 (Interleukin 17) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of IL-17 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of TGF-ß1 on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of IF? (Interferon gamma) on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of IF? on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of PIBF on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of PIBF on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of IL-4 (Interleukin 4) on the day before embryo transfer	Blood levels of IL-4 on the day before embryo transfer	1 day
Primary	Blood levels of IL-10 (Interleukin 10) on the day before embryo transfer	Blood levels of IL-10 on the day before embryo transfer	1 day
Primary	Blood levels of IL-17 (Interleukin 17) on the day before embryo transfer	Blood levels of IL-17 on the day before embryo transfer	1 day
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day before embryo transfer	Blood levels of TGF-ß1 on the day before embryo transfer	1 day
Primary	Blood levels of IF? (Interferon gamma) on the day before embryo transfer	Blood levels of IF? on the day before embryo transfer	1 day
Primary	Blood levels of PIBF (Progesterone induced blocking factor) on the day before embryo transfer	Blood levels of PIBF on the day before embryo transfer	1 day
Primary	Blood levels of IL-4 (Interleukin 4) on the day of embryo transfer	Blood levels of IL-4 on the day of embryo transfer	1 day
Primary	Blood levels of IL-10 (Interleukin 10) on the day of embryo transfer	Blood levels of IL-10 on the day of embryo transfer	1 day
Primary	Blood levels of IL-17 (Interleukin 17) on the day of embryo transfer	Blood levels of IL-17 on the day of embryo transfer	1 day
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) on the day of embryo transfer	Blood levels of TGF-ß1 on the day of embryo transfer	1 day
Primary	Blood levels of IF? (Interferon gamma) on the day of embryo transfer	Blood levels of IF? on the day of embryo transfer	1 day
Primary	Blood levels of PIBF (Progesterone induced blocking factor) on the day of embryo transfer	Blood levels of PIBF on the day of embryo transfer	1 day
Primary	Blood levels of IL-4 (Interleukin 4) three days after embryo transfer	Blood levels of IL-4 three days after embryo transfer	3 days
Primary	Blood levels of IL-10 (Interleukin 10) three days after embryo transfer	Blood levels of IL-10 three days after embryo transfer	3 days
Primary	Blood levels of IL-17 (Interleukin 17) three days after embryo transfer	Blood levels of IL-17 three days after embryo transfer	3 days
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) three days after embryo transfer	Blood levels of TGF-ß1 three days after embryo transfer	3 days
Primary	Blood levels of IF? (Interferon gamma) three days after embryo transfer	Blood levels of IF? three days after embryo transfer	3 days
Primary	Blood levels of PIBF (Progesterone induced blocking factor) three days after embryo transfer	Blood levels of PIBF three days after embryo transfer	3 days
Primary	Blood levels of IL-4 (Interleukin 4) ten days after embryo transfer	Blood levels of IL-4 ten days after embryo transfer	10 days
Primary	Blood levels of IL-10 (Interleukin 10) ten days after embryo transfer	Blood levels of IL-10 ten days after embryo transfer	10 days
Primary	Blood levels of IL-17 (Interleukin 17) ten days after embryo transfer	Blood levels of IL-17 ten days after embryo transfer	10 days
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) ten days after embryo transfer	Blood levels of TGF-ß1 ten days after embryo transfer	10 days
Primary	Blood levels of IF? (Interferon gamma) ten days after embryo transfer	Blood levels of IF? ten days after embryo transfer	10 days
Primary	Blood levels of PIBF (Progesterone induced blocking factor) ten days after embryo transfer	Blood levels of PIBF ten days after embryo transfer	10 days
Primary	Blood levels of IL-4 (Interleukin 4) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of IL-4 in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of IL-10 (Interleukin 10) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of IL-10 in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of IL-17 (Interleukin 17) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of IL-17 in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of TGF-ß1 (Transforming Growth Factor beta1) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of TGF-ß1 in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of IF? (Interferon gamma) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of IF? in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of PIBF (Progesterone induced blocking factor) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of PIBF in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of estradiol on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of estradiol on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of progesterone on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	Blood levels of progesterone on the on the day of progesterone rise (NC) or first day of progesterone administration (HRT)	1 day
Primary	Blood levels of estradiol on the day before embryo transfer	Blood levels of estradiol on the day before embryo transfer	1 day
Primary	Blood levels of progesterone on the day before embryo transfer	Blood levels of progesterone on the day before embryo transfer	1 day
Primary	Blood levels of estradiol on the day of embryo transfer	Blood levels of estradiol on the day of embryo transfer	1 day
Primary	Blood levels of progesterone on the day of embryo transfer	Blood levels of progesterone on the day of embryo transfer	1 day
Primary	Blood levels of estradiol three days after embryo transfer	Blood levels of estradiol three days after embryo transfer	3 days
Primary	Blood levels of progesterone three days after embryo transfer	Blood levels of progesterone three days after embryo transfer	3 days
Primary	Blood levels of estradiol ten days after embryo transfer	Blood levels of estradiol ten days after embryo transfer	10 days
Primary	Blood levels of progesterone ten days after embryo transfer	Blood levels of progesterone ten days after embryo transfer	10 days
Primary	Blood levels of estradiol in case of pregnancy at 5 weeks +/- 3 days	Blood levels of estradiol in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of progesterone in case of pregnancy at 5 weeks +/- 3 days	Blood levels of progesterone in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Primary	Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) three days after embryo transfer	Blood levels of ß-hCG three days after embryo transfer	3 days
Primary	Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) ten days after embryo transfer	Blood levels of ß-hCG ten days after embryo transfer	10 days
Primary	Blood levels of ß-hCG (Beta-Human Chorionic Gonadotropin) in case of pregnancy at 5 weeks +/- 3 days	Blood levels of ß-hCG in case of pregnancy at 5 weeks +/- 3 days	5 weeks
Secondary	Pregnancy rate	Number of patients with a ß-hCG > 5 IU out of the number of patients who underwent an embryo transfer.	10 days
Secondary	Clinical pregnancy rate	Number of patients with an ultrasonographic visible sac out of the number of patients who underwent an embryo transfer	5 weeks and 3 days
Secondary	Miscarriage rate	Number of patients with a pregnancy loss out of the number of patients who had a ß-hCG > 5 IU after embryo transfer	12 weeks