Estrofem

Manufactured by Novo Nordisk

Sourced in Denmark

Estrofem is a laboratory equipment product manufactured by Novo Nordisk. It is designed for the measurement and analysis of estrogen levels in biological samples.

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Lab products found in correlation

Crinone, by Merck Group (2 mentions) Progynova, by Bayer (1 mentions) Lucrin, by Abbott (1 mentions) Lutinus, by Ferring (1 mentions) Endometrin, by Ferring (1 mentions)

Spelling variants of this product

Estrofem 2 mg (2 citations)

13 protocols using estrofem

Hormone-Mediated Frozen Embryo Transfer

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Frozen cycles were conducted based on hormone therapy or ovulatory cycles. In both cases, on the third day of menstruation, transvaginal ultrasonography was performed to evaluate endometrial thickness and ovarian status. Hormonal treatment was 2 mg oral estradiol valerate TID (three times a day) (either Progynova, Bayer HealthCare, Germany, or Estrofem Novo Nordisk a/S, Denmark). Transvaginal ultrasonography was performed again 7 days later and the hormone dose was adjusted depending on the endometrial thickness. When the endometrial thickness was ≥7 mm, progesterone was added for luteal preparation. Embryos were transferred after progesterone supplementation, based on their developmental stage.
The ovulatory cycles followed the development of the dominant follicle, and the decision for either a natural cycle with spontaneous ovulation or ovulation triggering with Ovitrelle was based on the timing of the transfer (avoiding weekend transfers) and based on blood levels of luteinizing hormone and appropriate follicular diameter.

Shibli Abu Raya Y., Bilgory A., Aslih N., Atzmon Y., Shavit M., Estrada D., Sharqawi M, & Shalom-Paz E. (2023). High initial β-hCG predicts IVF outcomes accurately and precludes the need for repeated measurements. Endocrine Connections, 12(11), e230189.

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Cryopreserved Euploid Blastocyst Transfer

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Single euploid blastocyst transfer was carried out in a cryopreserved embryo transfer cycle in all patients.
Artificial cycle with gonadotrophin releasing hormone agonist (GnRHa) suppression was used for preparation of endometrium in all patients. Briefly, GnRHa (Lucrin, Abbott, Istanbul, Turkey) was started on day 21 of the preceding cycle; oral contraceptive pre-treatment was used along with GnRHa in patients with irregular cycles. Oral oestrogen (Estrofem; Novo Nordisk, Istanbul, Turkey) was commenced on the second or third day of the menstrual cycle, with incremental dosing scheme from 2 mg/day to 6 mg/day. After 12-14 days of oestrogen use, transvaginal ultrasonographic examination was carried out to confirm that bi-layer endometrial thickness was more than 7 mm during which vaginal progesterone gel (Crinone; Merck Sereno, Bedfordshire, UK) twice a day is commenced. Embryo transfer is scheduled on the 6th day of starting progesterone. Luteal support was continued up to 10th week of gestational age in conception cycles.
Clinical pregnancy was defined as visualization of gestational sac at transvaginal ultrasonographic examination. The main outcome measure was ongoing pregnancy, which was defined as pregnancy beyond 12 weeks of gestational age.

Mumusoglu S., Ozbek I.Y., Sokmensuer L.K., Polat M., Bozdag G., Papanikolaou E, & Yarali H. (2017). Duration of blastulation may be associated with ongoing pregnancy rate in single euploid blastocyst transfer cycles. Reproductive biomedicine online, 35(6).

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Frozen Embryo Transfer Protocol

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For the frozen embryo transfer cycle, euploid blastocysts were transferred to each patient. Blastocysts were warmed using the Kitazato thawing kit [56 (link)]. After warming, the blastocysts were transferred to G2 medium and cultured for 2–3 h. Blastocysts were transferred after prior endometrial preparation. The luteal phase was supplemented by transvaginal E2 administration (3 × 2 mg, Estrofem, Bagsvaerd, NovoNordisk) starting from day 2 of the cycle. When the endometrium reached >8 mm thickness, transvaginal P (3 × 100 mg Lutinus, Ferring) was administered. E2, P, and hCG hormone levels were verified every 3–4 days after the transfer.

Lukaszuk K, & Podolak A. (2022). Does Trophectoderm Mitochondrial DNA Content Affect Embryo Developmental and Implantation Potential?. International Journal of Molecular Sciences, 23(11), 5976.

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Blastocyst Transfer in Natural and Artificial Cycles

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In women with regular menstrual cycles, vitrified/warmed blastocysts were transferred into the uterus during natural cycles that were monitored with ultrasound and in which ovulation was confirmed based on urine LH tests. In patients with anovulatory or irregular cycles, warmed blastocysts were transferred in artificial cycles, in which the endometrium was prepared with oestradiol (Estrofem; Novo Nordisk, Denmark) and progesterone (Estima; Effik, France) without GnRH agonist suppression.

Kovačič B., Taborin M, & Vlaisavljević V. (2018). Artificial blastocoel collapse of human blastocysts before vitrification and its effect on re-expansion after warming - a prospective observational study using time-lapse microscopy. Reproductive biomedicine online, 36(2).

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Ovarian Response-Guided Luteal Support

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In cases of normal or moderate-high ovarian response (fewer than 20 oocytes) and lower risk of developing OHSS, patients with GnRHa trigger received a single subcutaneous bolus of 1500 IU hCG for luteal support one hour after the oocyte retrieval. Due to limited luteinization after GnRHa triggering, we used estradiol and progesterone to support the luteal phase.
The patients administered micronized vaginal progesterone 200 mg (Utrogestan, Medis or Estima, Effik) every 8 hours and oral estradiol 2 mg (Estrofem, Novo Nordisk A/S) every 8 hours from the first day of ovarian puncture until the 12 weeks of gestation.
In cases of excessive ovarian response (more than 20 oocytes) and/or high risk of OHSS, luteal support was not introduced and all good quality embryos were frozen on day 5 or 6.
All patients with hCG trigger received luteal support with micronized vaginal progesterone 200 mg (Utrogestan, Medis or Estima, Effik) every 8 hours from the first day of ovarian puncture until the day of the ultrasound confirmation of a vital pregnancy (i.e., day 28-30 after embryo transfer (ET)).

Abdulkhalikova D., Bokal E.V., Stimpfel M., Ciglar P, & Korosec S. (2022). Reproductive Outcome After GnRH Agonist Triggering With Co-Administration of 1500 IU hCG on the Day of Oocyte Retrieval in High Responders: A Long-Term Retrospective Cohort Study. Frontiers in Endocrinology, 13, 826411.

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Endometrial Preparation for Frozen Blastocyst Transfer

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A GnRH agonist (GnRHa) protocol was used to programme the start of endometrial preparation, with a half dose (≈1.88 mg) of a Lucrin depot (3.75 mg, Leuprorelin acetate, Abbott, Mumbai, India) administered on oocyte retrieval +7 (Isikoglu et al., 2007; Ozgur et al., 2016) and oestrogen (2 mg, Estrofem, Novo Nordisk, Istanbul, Turkey) supplementation started 8 to 10 days later. Oestrogen supplementation followed a threephase step-up regimen: 2 mg for days 1 to 6, 4 mg for days 7 to 10, and 8 mg for days 11 to 14. On the 14th day of oestrogen a transvaginal ultrasound scan was performed to measure endometrial thickness and blood was taken to measure serum progesterone concentration. Arbitrarily, an endometrial thick-ness of >7 mm and a serum progesterone concentration of <2 ng/ml was preferred. If these arbitrary measures were satisfied, oestrogen supplementation was continued and progesterone (8% twice a day, Crinone, Merck Serono, Istanbul, Turkey) supplementation was started the following day (15th day). All vitrified-warmed blastocyst transfers were performed on progesterone +5.

Ozgur K., Bulut H., Berkkanoglu M., Humaidan P, & Coetzee K. (2016). Concurrent oocyte retrieval and hysteroscopy: a novel approach in assisted reproduction freeze-all cycles. Reproductive biomedicine online, 33(2).

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Frozen Embryo Transfer Endometrial Priming

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Participants in the frozen ET group underwent endometrial priming with oral 6.0 mg/daily estradiol (Estrofem; Novo Nordisk, Denmark). It began on day 3 of menses and continued for 10-14 days. E2 patch supplementation was used if needed. Priming was continued until the endometrial thickness reached at least 8 mm. Luteal phase support was given to both the fresh and frozen ET group with vaginal P gel (Crinone; Merck Serono, Turkey). P gel was used twice a day beginning from five days before the thawing and continued until week 12.

Erşahin A.A., Acet M., Erşahin S.S, & Dokuzeylül Güngör N. (2017). Frozen embryo transfer prevents the detrimental effect of high estrogen on endometrium receptivity. Journal of the Turkish German Gynecological Association, 18(1), 38-42.

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Endometrial Preparation for Frozen Embryo Transfer

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Endometrial preparation for FET involved HRT. Briefly, each woman was administered oral oestrodiol (Estrofem, Novo Nordisk, Istanbul, Turkey) in a step-up regimen (4 mg/day on days 1–4, 6 mg/day on days 5–8, and 8 mg/day on days 9–12). Transvaginal ultrasonography (TV-USG) (GE Ultrasound Korea Ltd., Korea, Model; Voluson S6) was performed on day 13 to measure endometrial thickness, and the cycle was cancelled if the endometrial thickness was < 7 mm. The serum P level was also measured, and the embryo transfer was cancelled if this concentration was > 1 ng/ml. Oral oestrodiol supplementation was continued at 8 mg/day, and IM administration of 100 mg of P (Progestan, Koçak Farma,Turkey) was started. Embryo transfer was performed on the 6th day of progesterone administration. Oral oestrodiol was continued until the 7th week, and IM P administration was continued until the 10th week of pregnancy.

Boynukalin F.K., Gultomruk M., Turgut E., Demir B., Findikli N., Serdarogullari M., Coban O., Yarkiner Z, & Bahceci M. (2019). Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers. Reproductive Biology and Endocrinology : RB&E, 17, 102.

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Endometrial Preparation Protocol for Embryo Transfer

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Endometrial preparation for ET involved hormone replacement therapy. Briefly, each woman was given oral estrogen (Estrofem, Novo Nordisk, Istanbul, Turkey) in a step-up regime: 4 mg/day on days 1–4, 6 mg/day on days 5–8, and 8 mg/day on days 9–12. TV-USG was performed on day 13 to measure endometrial thickness. The serum P concentration was also measured, and cycles were cancelled if the concentration was >1.5 ng/ml. Estrogen supplementation was continued at 8 mg/day, and 50-mg daily IM P (Progestan, Koçak Farma, Turkey) supplementation was started [22 (link)]. ET was performed on the 6^th day of P administration. Oral estrogen was continued until the 7^th week of pregnancy, and IM progesterone was continued until the 9^th week of pregnancy.

Boynukalin F.K., Turgut N.E., Gultomruk M., Ecemis S., Yarkiner Z., Findikli N, & Bahceci M. (2020). Impact of elective frozen vs. fresh embryo transfer strategies on cumulative live birth: Do deleterious effects still exist in normal & hyper responders?. PLoS ONE, 15(6), e0234481.

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Artificial Cycles-FET Hormone Protocol

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USG evaluation was performed on the second day of menstruation to assess the presence of ovarian cysts or other pelvic pathologies. An artificial cycles-FET hormonal replacement protocol with estradiol (Estrofem 2 mg; Novo Nordisk, Bagsvaerd, Denmark) from days 2 or 3 of menstruation was performed for endometrial preparation of all FETs.^{[24 (link)]} The USG was repeated on days 10 or 11, depending on the patient menstrual cycle length. We evaluated endometrial thickness, and endometrial pattern, and the presence of any spontaneously growing dominant follicles. When the endometrial thickness was ≥8 mm, Vaginal Natural Micronized Progesterone (Progestan 200 mg; Koçak, Turkey) was started (3 times per day). ET was performed after administering vaginal progesterone for a total of 5 days.

Kavrut M., Sagir F.G, & Atayurt Z. (2023). Large-scale retrospective analysis of methodological factors affecting pregnancy rates after embryo transfer for in vitro fertilization. Medicine, 102(36), e35146.

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