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The goal of this clinical trial is to learn whether different natural approaches to preparing the uterus for frozen embryo transfer (FET) can improve pregnancy success in women undergoing in vitro fertilization (IVF) treatment.
The main questions it aims to answer are:
Researchers will compare four different approaches to see which one results in the highest chance of achieving a clinical pregnancy, confirmed by ultrasound.
Participants will:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| True Natural Cycle Without Letrozole | Experimental | Participants undergo frozen embryo transfer in a true natural menstrual cycle without the use of either an aromatase inhibitor or ovulation trigger medication. Ovulation is monitored by ultrasound and serum hormone levels. Luteal phase support (vaginal progesterone 200 mg twice daily or subcutaneous progesterone 25 mg once daily) is initiated on the day of ultrasound-confirmed ovulation and continued until 12 weeks of gestation if pregnancy occurs. |
|
| True Natural Cycle With Letrozole | Experimental | Participants undergo frozen embryo transfer (FET) in a true natural menstrual cycle with administration of the aromatase inhibitor letrozole (2.5 mg twice daily) from cycle days 3-7. Ovulation is monitored by ultrasound and serum hormone levels. Luteal phase support (vaginal progesterone 200 mg twice daily or subcutaneous progesterone 25 mg once daily) is initiated on the day of ultrasound-confirmed ovulation and continued until 12 weeks of gestation if pregnancy occurs. |
|
| Modified Natural Cycle Without Letrozole | Experimental | Participants undergo frozen embryo transfer in a modified natural menstrual cycle without the use of an aromatase inhibitor. When the dominant follicle reaches ≥17 mm and endometrial thickness is ≥7 mm, and after exclusion of a spontaneous LH surge by serum measurement, ovulation is triggered with recombinant human chorionic gonadotropin (hCG) 250 mcg. Luteal phase support (vaginal progesterone 200 mg twice daily or subcutaneous progesterone 25 mg once daily) is initiated 2 days after ovulation trigger and continued until 12 weeks of gestation if pregnancy occurs. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Letrozole (Aromatase Inhibitors) | Drug | Letrozole 2.5 mg administered orally twice daily from cycle days 3-7 during the early follicular phase. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Pregnancy Rate | Number of pregnancies with an ultrasound-confirmed gestational sac per embryo transfer. | Approximately 4-6 weeks after embryo transfer. |
| Measure | Description | Time Frame |
|---|---|---|
| Biochemical Pregnancy Rate | Number of pregnancies with elevated serum beta-human chorionic gonadotropin (β-hCG) levels measured two weeks after embryo transfer, per embryo transfer. | Two weeks after embryo transfer. |
| Implantation Rate |
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Inclusion Criteria:
Exclusion Criteria:
Cisgender
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jelena Vukovic, MD | Contact | +381643070647 | jel.zor@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Specialized Gynecological Hospital "Ferona" Novi Sad | Novi Sad | 21000 | Serbia |
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| Modified Natural Cycle With Letrozole | Experimental | Participants undergo frozen embryo transfer (FET) in a modified natural menstrual cycle with administration of letrozole (2.5 mg twice daily) from cycle days 3-7. Ultrasound monitoring begins between cycle days 8-10. When the dominant follicle reaches ≥17 mm and endometrial thickness is ≥7 mm, and after exclusion of a spontaneous LH surge by serum LH measurement, ovulation is triggered with recombinant human chorionic gonadotropin (hCG) 250 mcg. Luteal phase support (vaginal progesterone 200 mg twice daily or subcutaneous progesterone 25 mg once daily) is initiated 2 days after ovulation trigger and continued until 12 weeks of gestation if pregnancy occurs. |
|
| Choriogonadotropin alpha (r-hCG) | Drug | Recombinant human chorionic gonadotropin (hCG) 250 mcg administered subcutaneously to trigger ovulation when follicular and endometrial criteria are met. |
|
| Progesterone | Drug | Luteal phase support with either vaginal progesterone 200 mg twice daily or subcutaneous progesterone 25 mg once daily, initiated after ovulation (or 2 days after hCG trigger) and continued until 12 weeks of gestation if pregnancy occurs. |
|
Number of ultrasound-confirmed gestational sacs divided by the number of embryos transferred.
| Approximately 4-6 weeks after embryo transfer. |
| Miscarriage Rate | Pregnancy loss before 23 completed weeks of gestation, expressed per embryo transfer. | Up to 23 weeks of gestation. |
| ID | Term |
|---|---|
| D007247 | Infertility, Female |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D007246 | Infertility |
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| ID | Term |
|---|---|
| D000077289 | Letrozole |
| D047072 | Aromatase Inhibitors |
| D006063 | Chorionic Gonadotropin |
| D011374 | Progesterone |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D065088 | Steroid Synthesis Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D004965 | Estrogen Antagonists |
| D006727 | Hormone Antagonists |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D010926 | Placental Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011257 | Pregnancy Proteins |
| D011506 | Proteins |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D003339 | Corpus Luteum Hormones |
| D042341 | Gonadal Hormones |
| D045167 | Progesterone Congeners |
| D012739 | Gonadal Steroid Hormones |
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