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Trials
Published in: Trials 1/2012

Open Access 01-12-2012 | Study protocol

Duration of luteal support (DOLS) with progesterone pessaries to improve the success rates in assisted conception: study protocol for a randomized controlled trial

Authors: Rafet Gazvani, Richard Russell, Yasmin Sajjad, Zarko Alfirevic

Published in: Trials | Issue 1/2012

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Abstract

Background

Luteal support with progesterone is necessary for successful implantation of the embryo following egg collection and embryo transfer in an in-vitro fertilization (IVF) cycle. Progesterone has been used for as little as 2 weeks and for as long as 12 weeks of gestation. The optimal length of treatment is unresolved at present and it remains unclear how long to treat women receiving luteal supplementation.

Design

The trial is a prospective, randomized, double-blind, placebo-controlled trial to investigate the effect of the duration of luteal support with progesterone in IVF cycles. Following 2 weeks standard treatment and a positive biochemical pregnancy test, this randomized control trial will allocate women to a supplementary 8 weeks treatment with vaginal progesterone or 8 weeks placebo. Further studies would be required to investigate whether additional supplementation with progesterone is beneficial in early pregnancy.

Discussion

Currently at the Hewitt Centre, approximately 32.5% of women have a positive biochemical pregnancy test 2 weeks after embryo transfer. It is this population that is eligible for trial entry and randomization. Once the patient has confirmed a positive urinary pregnancy test they will be invited to join the trial. Once the consent form has been completed by the patient a trial prescription sheet will be sent to pharmacy with a stated collection time. The patient can then be randomized and the drugs dispensed according to pharmacy protocol. A blood sample will then be drawn for measurement of baseline hormone levels (progesterone, estradiol, free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A, Activin A, Inhibin A and Inhibin B). The primary outcome measure is the proportion of all randomized women that continue successfully to a viable pregnancy (at least one fetus with fetal heart rate >100 beats/minute) on transabdominal/transvaginal ultrasound at 10 weeks post embryo transfer/12 weeks gestation (that is at the end of 8 weeks supplementary trial treatment).

Trial registration

ISRCTN05696887
Literature
1.
Edwards RG, Steptoe PC, Purdy JM: Establishing full-term human pregnancies using cleaving embryos grown in vitro. Br J Obstet Gynaecol. 1980, 87: 737-756. 10.1111/j.1471-0528.1980.tb04610.x.CrossRefPubMed
2.
Smitz J, Bourgain C, Van Waesberghe L, Camus M, Devroey P, Van Steirteghem AC: A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation. Hum Reprod. 1993, 8: 40-45.PubMed
3.
Smitz J, Erard P, Camus M, Devroey P, Tournaye H, Wisanto A, Van Steirteghem AC: Pituitary gonadotrophin secretory capacity during the luteal phase in superovulation using GnRH-agonists and HMG in a desensitization or flare-up protocol. Hum Reprod. 1992, 7: 1225-1229.CrossRefPubMed
4.
Ludwig M, Diedrich K: Evaluation of an optimal luteal phase support protocol in IVF. Acta Obstet Gynecol Scand. 2001, 80: 452-466. 10.1034/j.1600-0412.2001.080005452.x.CrossRefPubMed
5.
Broekmans FJ, Bernardus RE, Berkhout G, Schoemaker J: Pituitary and ovarian suppression after early follicular and mid-luteal administration of a LHRH agonist in a depot formulation: decapeptyl CR. Gynecol Endocrinol. 1992, 6: 153-161. 10.3109/09513599209015549.CrossRefPubMed
6.
Smitz J, Devroey P, Camus M, Deschacht J, Khan I, Staessen C, Van Waesberghe L, Wisanto A, Van Steirteghem AC: The luteal phase and early pregnancy after combined GnRH-agonist/HMG treatment for superovulation in IVF or GIFT. Hum Reprod. 1988, 3: 585-590.CrossRefPubMed
7.
Daya S, Gunby J: Luteal phase support in assisted reproduction cycles. The Cochrane Library. 2004, NJ, USA: John Wiley and Sons Ltd
8.
Abramowicz JS, Archer DF: Uterine endometrial peristalsis – a transvaginal ultrasound study. Fertil Steril. 1990, 54: 451-454.CrossRefPubMed
9.
Fanchin R, Righini C, Olivennes F, Taylor S, de Ziegler D, Frydman R: Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum Reprod. 1998, 13: 1968-1974. 10.1093/humrep/13.7.1968.CrossRefPubMed
10.
Soliman S, Daya S, Collins J, Hughes EG: The role of luteal phase support in infertility treatment: a meta-analysis of randomized trials. Fertil Steril. 1994, 61: 1068-1076.CrossRefPubMed
11.
Penzias AS: Luteal phase support. Semin Reprod Endocrinol. 1995, 13: 32-38. 10.1055/s-2007-1016340.CrossRef
12.
Herman A, Ron-El R, Golan A, Raziel A, Soffer Y, Caspi E: Pregnancy rate and ovarian hyperstimulation after luteal human chorionic gonadotropin in in vitro fertilization stimulated with gonadotropin-releasing hormone analog and menotropins. Fertil Steril. 1990, 53: 92-96.CrossRefPubMed
13.
Arafat ES, Hargrove JT, Maxson WS, Desiderio DM, Wentz AC, Andersen RN: Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites. Am J Obstet Gynecol. 1988, 159: 1203-1209.CrossRefPubMed
14.
Friedler S, Raziel A, Schachter M, Strassburger D, Bukovsky I, Ron-El R: Luteal support with micronized progesterone following in-vitro fertilization using a down-regulation protocol with gonadotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration. Hum Reprod. 1999, 14: 1944-1948. 10.1093/humrep/14.8.1944.CrossRefPubMed
15.
Licciardi FL, Kwiatkowski A, Noyes NL, Berkeley AS, Krey LL, Grifo JA: Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study. Fertil Steril. 1999, 71: 614-618. 10.1016/S0015-0282(98)00515-9.CrossRefPubMed
16.
Bourgain C, Devroey P, Van Waesberghe L, Smitz J, Van Steirteghem AC: Effects of natural progesterone on the morphology of the endometrium in patients with primary ovarian failure. Hum Reprod. 1990, 5: 537-543.PubMed
17.
Devroey P, Palermo G, Bourgain C, Van Waesberghe L, Smitz J, Van Steirteghem AC: Progesterone administration in patients with absent ovaries. Int J Fertil. 1989, 34: 188-193.PubMed
18.
Smitz J, Devroey P, Faguer B, Bourgain C, Camus M, Van Steirteghem AC: A prospective randomized comparison of intramuscular or intravaginal natural progesterone as a luteal phase and early pregnancy supplement. Hum Reprod. 1992, 7: 168-175.CrossRefPubMed
19.
Kline DG, Kim D, Midha R, Harsh C, Tiel R: Management and results of sciatic nerve injuries: a 24-year experience. J Neurosurg. 1998, 89: 13-23. 10.3171/jns.1998.89.1.0013.CrossRefPubMed
20.
Bulletti C, de Ziegler D, Flamigni C, Giacomucci E, Polli V, Bolelli G, Franceschetti F: Targeted drug delivery in gynaecology: the first uterine pass effect. Hum Reprod. 1997, 12: 1073-1079. 10.1093/humrep/12.5.1073.CrossRefPubMed
21.
Cicinelli E, de Ziegler D, Bulletti C, Matteo MG, Schonauer LM, Galantino P: Direct transport of progesterone from vagina to uterus. Obstet Gynecol. 2000, 95: 403-406. 10.1016/S0029-7844(99)00542-6.PubMed
22.
Fanchin R, De Ziegler D, Bergeron C, Righini C, Torrisi C, Frydman R: Transvaginal administration of progesterone. Obstet Gynecol. 1997, 90: 396-401. 10.1016/S0029-7844(97)00270-6.CrossRefPubMed
23.
Nakajima ST, Nason FG, Badger GJ, Gibson M: Progesterone production in early pregnancy. Fertil Steril. 1991, 55: 516-521.CrossRefPubMed
24.
Wolf A, Wood EG, Batzer FR: The Luteo-placental shift: observation on its occurrence with Crinone treatment. Fertil Steril. 1998, 70 (Suppl 1): S396.a-
Metadata
Title
Duration of luteal support (DOLS) with progesterone pessaries to improve the success rates in assisted conception: study protocol for a randomized controlled trial
Authors
Rafet Gazvani
Richard Russell
Yasmin Sajjad
Zarko Alfirevic
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Trials / Issue 1/2012
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-13-118

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