Does ovarian stimulation influence embryo quality?

By (gynecologist), (embryologist) and (psychologist).
Last Update: 12/15/2021

Embryo quality can be influenced by several factors, many of them directly related to the quality of the gametes (oocytes and sperm). These factors that condition embryo quality can be internal, such as the cause of infertility; or external, where we find the ovarian stimulation protocols used in assisted reproduction techniques.

In in vitro fertilization (IVF) cycles, a controlled ovarian stimulation is performed with a hormonal treatment, whose objective is to stimulate the ovary to obtain an adequate number of oocytes to increase the probability of success.

However, it has been questioned whether these hormones administered exogenously during ovarian stimulation may have a negative effect on oocyte quality and, therefore, have an impact on embryo quality.

Oocyte maturation

The oocyte maturation process occurs during follicular development and is where the oocyte is provided with all the factors necessary for normal fertilization and embryo development.

For this, the oocyte has to mature both at the nucleus and cytoplasmic level. Any alteration of one of these two maturation processes can compromise the quality of the oocyte and, therefore, that of the future embryo.

However, oocyte maturation during ovarian stimulation protocols does not occur physiologically but is influenced by the hormonal treatments administered to achieve the development of a greater number of follicles.

Because of this, several authors have considered the possible effect of ovarian stimulation on oocyte and embryo quality.

Stimulated vs. unstimulated cycles

Studying embryos from a natural conception involves ethical and moral issues. For this reason, the approach taken in several studies to try to ascertain the effect of ovarian stimulation on embryo quality has been to compare stimulated cycles with unstimulated cycles.

In one of these studies, embryo division and embryo quality were analyzed in stimulated and unstimulated cycles. The conclusion was that the gonadotropin administration of the stimulation protocol (long protocol with GnRH agonists and FSH) was not reflected in the cleavage capacity nor in the quality of the resulting embryos compared to unstimulated cycles. However, because of the study design, it is possible that a minor impact on embryonic development could not be detected.

Another study focused on evaluating chromosomal alterations (aneuploidies) in unstimulated cycles and in cycles with moderate ovarian stimulation. The results suggest that the rate of embryonic aneuploidy is not increased with moderate ovarian stimulation in the population of young (donor) women studied compared to the unstimulated cycle. Despite this, the group of women in the study was small, so the results are not conclusive.

Different doses of gonadotropins

Some authors have chosen to study the effect of ovarian stimulation on embryo quality by comparing different stimulation protocols.

One study compared chromosomal alterations in embryos obtained after gentle ovarian stimulation with embryos obtained from conventional ovarian stimulation. While gentle stimulation resulted in a reduction in the number of available oocytes and embryos, the proportion of chromosomally normal embryos was lower after conventional ovarian stimulation. Therefore, these results may suggest that higher doses of gonadotropins may increase the proportion of aneuploidies.

However, as a greater number of embryos were obtained with conventional ovarian stimulation, the number of chromosomally normal embryos obtained per patient was similar after both stimulation protocols.

Further studies are needed to clarify the role of ovarian stimulation on embryo quality and thus support the use of a gentle or conventional stimulation protocol.

In general, it is suggested that mild ovarian stimulation protocols are associated with better-quality embryos. For this reason, although fewer oocytes are recovered with gentle ovarian stimulation, the number of good-quality embryos may be comparable to that obtained with higher doses.

Protocol customization

The personalization of the ovarian stimulation protocol for each patient acquires great importance, also when it comes to embryo quality. Therefore, the specialist must take into account the circumstances of each patient to decide one protocol or the other, always avoiding aggressive stimulation protocols.

Assisted procreation, as any other medical treatment, requires that you rely on the professionalism of the doctors and staff of the clinic you choose. Obviously, each clinic is different. Get now your Fertility Report, which will select several clinics for you out of the pool of clinics that meet our strict quality criteria. Moreover, it will offer you a comparison between the fees and conditions each clinic offers in order for you to make a well informed choice.

A mild protocol may have certain advantages, such as the lower risk of ovarian hyperstimulation syndrome, fewer injections, and lower cost. However, gentle ovarian stimulation may also have disadvantages such as a higher cancellation rate or a lower number of surplus embryos available for vitrification.

FAQs from users

Can ovarian stimulation affect egg quality?

By Rut Gómez de Segura M.D. (gynecologist).

No. Some studies have tried to show that high doses of medication could worsen oocyte quality, but this has not been proven.

It is true that patients with low ovarian reserve usually take high doses of medication and have poor oocyte quality. This poor oocyte quality is associated with the low ovarian reserve, not with the doses of medication.

Are IVF embryos of poorer quality than those obtained from natural conception?

By Silvia Azaña Gutiérrez B.Sc., M.Sc. (embryologist).

Embryos from natural conception cannot be analyzed due to the ethical and moral implications that this implies. Therefore, several authors have chosen to compare embryos obtained after stimulated and unstimulated IVF cycles.

The results were that the quality of the embryos seems similar in both study groups, although more studies are needed to confirm this.

If you want to learn more about ovarian stimulation, you can visit the following link: What is ovarian stimulation - Process, medications, and symptoms.

If you want to continue reading in-depth about embryo quality, we recommend you to read this article: Embryo quality for embryo transfer or embryo freezing

We make a great effort to provide you with the highest quality information.

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Alper MM, Fauser BC. Ovarian stimulation protocols for IVF: is more better than less? Reprod Biomed Online. 2017 Apr;34(4):345-353.

Arce JC, Andersen AN, Fernández-Sánchez M, Visnova H, Bosch E, García-Velasco JA, Barri P, de Sutter P, Klein BM, Fauser BC. Ovarian response to recombinant human follicle-stimulating hormone: a randomized, antimüllerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2014 Dec;102(6):1633-40.e5.

Baart EB, Martini E, Eijkemans MJ, Van Opstal D, Beckers NG, Verhoeff A, Macklon NS, Fauser BC. Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod. 2007 Apr;22(4):980-8.

Bosch E, Labarta E, Kolibianakis E, Rosen M, Meldrum D. Regimen of ovarian stimulation affects oocyte and therefore embryo quality. Fertil Steril. 2016 Mar;105(3):560-570.

Labarta E, Bosch E, Alamá P, Rubio C, Rodrigo L, Pellicer A. Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles. J Clin Endocrinol Metab. 2012 Oct;97(10):E1987-94.

Nargund G, Datta AK, Fauser BCJM. Mild stimulation for in vitro fertilization. Fertil Steril. 2017 Oct;108(4):558-567.

Verberg MF, Eijkemans MJ, Macklon NS, Heijnen EM, Baart EB, Hohmann FP, Fauser BC, Broekmans FJ. The clinical significance of the retrieval of a low number of oocytes following mild ovarian stimulation for IVF: a meta-analysis. Hum Reprod Update. 2009 Jan-Feb;15(1):5-12.

Verberg MF, Macklon NS, Nargund G, Frydman R, Devroey P, Broekmans FJ, Fauser BC. Mild ovarian stimulation for IVF. Hum Reprod Update. 2009 Jan-Feb;15(1):13-29.

Ziebe S, Bangsbøll S, Schmidt KL, Loft A, Lindhard A, Nyboe Andersen A. Embryo quality in natural versus stimulated IVF cycles. Hum Reprod. 2004 Jun;19(6):1457-60.

FAQs from users: 'Can ovarian stimulation affect egg quality?' and 'Are IVF embryos of poorer quality than those obtained from natural conception?'.

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Authors and contributors

 Rut Gómez de Segura
Rut Gómez de Segura
Graduation in Medicine and Surgery from the University of Alcalá de Henares. Specialization in Obstetrics and Gynecology at the Hospital Costa del Sol in Marbella. Dr Rut Gómez de Segura currently works as medical director in the fertility center ProcreaTec in Madrid. More information about Rut Gómez de Segura
Licence number: 28/2908776
 Silvia Azaña Gutiérrez
Silvia Azaña Gutiérrez
B.Sc., M.Sc.
Graduate in Health Biology from the University of Alcalá and specialized in Clinical Genetics from the same university. Master in Assisted Reproduction by the University of Valencia in collaboration with IVI clinics. More information about Silvia Azaña Gutiérrez
License: 3435-CV
Adapted into english by:
 Cristina  Algarra Goosman
Cristina Algarra Goosman
B.Sc., M.Sc.
Graduated in Psychology by the University of Valencia (UV) and specialized in Clinical Psychology by the European University Center and specific training in Infertility: Legal, Medical and Psychosocial Aspects by University of Valencia (UV) and ADEIT.
More information about Cristina Algarra Goosman
Member number: CV16874

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