Insights from clinical experience in treating IVF poor responders

Poor responders is a term used to describe a portion of infertile women who do not respond well to ovarian stimulation with gonadotrophins. While there is no standard definition of a poor responder, these women tend to be of advanced reproductive  age (≥40 years), have a history of diminished ovarian reserve manifested by poor ovarian response with conventional stimulation protocols. Despite the wide variability of conditions leading to infertility for this patient group, there are characteristics and needs common to many poor responders that can be addressed through a holistic approach. I recommend going to our webpage of to learn how to evaluate your ovarian reserve.

There really is hope to successfully have a baby when faced with poor ovarian response

Here I present an outlined synopsis of a recent review article “Insights from clinical experience in treating IVF poor responders” published in Reproductive Biomedicine Online, January, 2018.

You have free access to this article

1) Presenting mainstream IVF ovulation induction protocols for Poor Responders– The authors selected names for each protocol are a bit misleading (keep in mind medication FSH max daily dose is 450 IU/day).

A) All protocols have the following characteristics:

i) follow a GnRH antagonist protocol,

ii) are cycle day 2 starts of FSH medication,

iii) avoid ovarian over-suppressing agents such as pretreatment oral contraceptive pills or GnRH agonist Lupron (2 or more weeks),

iv) Give Ovidrel or Lupron trigger injection with a slightly smaller lead follicle size of 16 mm (rather than standard 18-20 mm)- earlier ovulation trigger (i.e. when the leading follicle is 16 mm) may improve the number and quality of embryos, as well as clinical pregnancy rates

B) Here’s a summary of the 3 protocols:

i) “Low Dose” (or “Mild”)- 300 U/day- combination FSH and Menopur.

ii) “Low Dose Clomiphene/FSH”- clomiphene 100 mg/day cycle days 2-7, Menopur 150 U/day days 2,4 and 6, then daily dose to day of Ovidrel or Lupron trigger.

iii) “Augmented Natural Cycle”- 150 U/day (75 U FSH/75 U Menopur)

C) Embryo Banking with multiple IVF cycles may offer advantage to acquire a good quality embryo before an FET cycle.

D) Caution for limited advantage of PGS for aneuploidy (PGD-A).

Objectively determined optimal stimulation protocols for poor responders do not exist in the literature. A Cochrane Review published in 2010 identified four comparison groups for modified ovarian stimulation in poor responders, but each was represented by only one trial and no significant differences between protocols were seen for clinical pregnancy and/or live birth rates.

2) Supplemental medications and substances– there is weak evidence supporting use of these supplements.

A) They suggest Human Growth Hormone (HGH) may offer an advantage with a trend towards this in the literature. The authors of this article do not present any protocol with use of HGH.

B) DHEAS supplement.

i) Reasoning for use of DHEAS: The ovary normally produces some testosterone which is required to be present for the follicle to convert it to estrogen and have normal follicle and egg development. It is possible that ovaries of woman with diminished ovarian reserve manufacture an insufficient amount of testosterone, thus hindering normal follicle and egg development.  DHEA has androgen (male) type hormone effects and is converted in the body/ovary to testosterone. Therefore, DHEA may serve to promote normal or near normal follicle and egg development.

ii) Given follicle and egg development may begin 4-6 months before the month which ovulation will occur, the authors recommend starting DHEAS therapy 6-8 weeks before the IVF ovulation induction cycle starts.

iii) Risks and side effects may outweigh benefits: Prolonged use of DHEA may have adverse “Male Hormone” side effects for women: such as acne, oily skin, deepening of the voice, hirsutism and hair loss. It is unclear whether any of these may be permanent.

iv) DHEA impacts the measurement of progesterone that are used to inform treatment decisions, leading to misinterpretation of medical tests and outcomes in the IVF centre and, thus, suboptimal treatment.

3) Alternative Medicine and Nutritional Supplements: Please read this section directly. There are a potpourri of remedies of which have been poorly investigated- Low evidence-based medical information to support any given intervention to be generalizable. Methods of stress reduction, counseling, group and individual support as well as daily support by nurses can be beneficial.

Finally, please keep in mind the authors may have some conflict of interests including financial gain that may introduce bias promoting dietary supplements such as DHEA. Specifically, . N Gleicher is a coinventor on numerous pending and awarded US patents claiming therapeutic benefits from androgen supplementation in women with low functional ovarian reserve and relating to the FMR1 gene in a diagnostic function in female fertility; is a coinventor on three pending AMH-related patent applications; is a shareholder/ receives royalties from Fertility Nutraceuticals, LLC.

I hope this review provides you with a broader perspective on care of the Poor Ovarian Responding patient- not just from hip to hip (ovaries), but from head (mind and emotions) to toe!