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International Journal of Reproductive BioMedicine
Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences of Yazd
ISSN: 1680-6433 EISSN: 2008-2177
Vol. 2, Num. 1, 2004, pp. 21-22

Iranian Journal of Reproductive Medicine, Vol. 2, No. 1, 2004, pp. 21-22

Editorial Comments

Dr. Mohammad A. Karimzadeh

Department of Obstetrics and Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Code Number: rm04005

Related Article: rm04004

I read with interest the paper by Hashemitabar et al. (2004) reporting "The Impact of Ovarian Stimulation and Luteal Phase Support on Embryo Quality and Implantation Process in Mice" and would like to comment on some of the methodological and clinical aspects of the study. Luteal  support is necessary in ovarian stimulation protocols, such as those commonly prescribed for in vitro fertilization and embryo transfer (smith et al.1989,Balaish-Allart et al.1990). Abnormal luteal function occurs when ovulation induction is induced with gonadotropins or when endogenous gonadotropins are suppressed with a gonadotropin-releasing hormone agonist (GnRH-a) (Olson et al.1983, al.1992b). Or granulosa cells of the follicles are removed or destroyed during oocytes retrieval, so steroid hormones secretion from the corpus luteom is impaired and luteal phase defect is occurred.

We feel that the paper by Hashemitabar et al. (2004) appears to have methodologically problems because the authors concluded that progesterone or hCG administration for luteal phase support have negative effects on implantation and embryo quality in mice. So, some questions are raised in this respect. First, the authors used only induction ovulation without oocytes retrieval and embryo transfer. However, I don't know how the responses of ovaries to gonadotropins was and how many embryos developed or arrested in the mice uterine? In addition, it is impossible to evaluate the effect of progesterone based on the number and embryo quality. The second, GnRH-a was not used for pituitary suppression in this study. As far as we know luteal phase defect has been demonstrated in cycles stimulated by using a protocol which contains GnRH-a, because reduced serum sex hormone level in luteal phase may influence embryo implantation in IVF-ET. In order to improve the clinical pregnancy rate, it is necessary to supply progesterone from the day of oocyte retrieval onwards to the IVF-ET patients.

Systematic review of the literature was performed to determine whether luteal phase support increases reproductive success in IVF cycles. A Meta-analyses were conducted when multiple homogeneous studies addressed a single issue. Luteal supplementation with either hCG or progesterone significantly improved fertility outcomes compared with no treatment  (Prittz.2002). Progesterone and hCG have both been used for this purpose, with comparable outcomes  (Martinez.2000). Progesterone is the product of choice; however, as it is associated with a lower incidence of ovarian hyperstimulation syndrome (OHSS). Its use is indicated up to the 12th weeks of pregnancy until placenta introduces steroidal hormones (Penzias, 2002).

In this study, the authors evaluated the effects of   progesterone, hCG or no treatment on the morphology of endometrium but not on the implantation  because we haven't know how many oocytes and embryo developed and  how many of them arrested. In the other studies, it has been shown that progesterone administrated is capable of reproducing all the endometrial changes normally seen in the luteal phase of menstrual cycle (Smitz et al,1992 , 1993).

On the other hand, I feel that we cannot extend these results to the ART treatment cycles in human. However, GnRH-a protocols necessitate the use of luteal phase support. Some researchers believe that hCG is better but it increased the risk of OHSS. After all, the relationship between progesterone, hCG and endometrium as well as embryo quality is more complex than the conclusion of the work by Hashemitabar et al. (2004). However, the use of progesterone or hCG is strongly recommended because  without supporting the luteal phase, the outcome of ART cycles are impaired.


  • Belaish-Allart J., and De Mouzon. J. (1990). The effect oh hCG supplementation after combined GnRH-agonist/hMG treatment in an IVF. Hum Repor 5:163-166.
  • Martinez F., Coroleu B., and Parera N. (2000). Human chorionic gonadotropins and intravaginal natural progesterone are equally effective for luteal phase support in IVF. Gynecol Endocrinol 14:316-320.
  • Olson J., Rebar. R., and Schreiber J. (1983). Shortened luteal phase after ovulation induction with human menopausal gonadotropin and hCG. Fertil Steril 39:284-291.
  • Smith E.M., and Anthony F.W. (1989). Trial of support treatment with human chorionic gonadotropin in the luteal phase after treatment with buserelin and human menoposal gonadotropin in women taking part in an IVF programme. Br Med J 298:1483-1489.
  • Smitz J., Devroey P., Faguer B., Bourgain C., Camus M., and Van Steirteghem A.C. (1992). A prospective randomized comparison of intramuscular or intravaginal natural progesterone as a luteal phase and early pregnancy supplement. Hum Repor 7:168-175.
  • Smitz J., Erad P., and Camus M. (1992b). Pituitary gonadotropin secretory capacity during the luteal phase in superovulaion using GnRH-a and hMG in desensitization or flare up protocol. 7:1225-1229.
  • Smitz J., Bourgain C., and Van Wasberghe L. (1993)  A prospective randomized study on estuarial valerate supplementation  in addition to intravaginal micronized progesterone in Buserelin and hMG induced superovulation. Hum Repor 8:40-45.
  •  Pritts E.A., and Atwood A.K. (2002) Luteal phase support in infertility treatment: a meta- analysis of the randomized trials. Hum. Reprod 17: 2287-2299.
  • Penzias A.S. (2002). Luteal phase support. Fertil Steril 77(2):318-323.

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