Overcoming challenges associated with poor ovarian response is a critical aspect of in vitro fertilization (IVF) for individuals classified as poor responders. Various strategies can be employed to enhance the chances of success in this particular group of patients. Firstly, individualized ovarian stimulation protocols play a crucial role. Tailoring medication dosages and adjusting the type of gonadotropins used based on the patient's age, ovarian reserve, and response to previous stimulation cycles is essential. Utilizing personalized approaches can optimize follicular development and improve egg yield. Co-administration of adjuvant medications is another effective strategy. Growth hormone supplementation has shown promise in enhancing ovarian response and improving the quality of eggs in poor responders. Additionally, androgen pre-treatment has been explored as a means to improve ovarian function and response to stimulation. Advancements in laboratory techniques, such as the use of time-lapse imaging systems, can aid in the selection of the most viable embryos for transfer. This ensures that the highest-quality embryos are chosen, increasing the chances of successful implantation. Embryo transfer techniques also play a significant role in optimizing success for poor responders. Employing the assisted hatching technique or using preimplantation genetic testing (PGT) to screen embryos for chromosomal abnormalities can improve implantation rates. In some cases, considering alternative approaches such as natural cycle IVF or minimal stimulation IVF may be beneficial for poor responders. These protocols aim to work with the patient's natural cycle or use lower doses of medications to reduce the risk of overstimulation and improve egg quality. Furthermore, addressing lifestyle factors that may impact fertility, such as nutrition, stress management, and adequate sleep, is crucial for optimizing outcomes in poor responders. In conclusion, a multifaceted approach is essential for improving success in poor responders undergoing IVF. By customizing ovarian stimulation protocols, incorporating adjuvant medications, leveraging advanced laboratory techniques, optimizing embryo transfer, and considering alternative protocols, fertility specialists can enhance the chances of a positive outcome for individuals facing the challenge of poor ovarian response.

1. Strategies to
improve Ovarian
Response in Poor
Responders
Dr Kaberi Banerjee

2. • Bologna Criteria

3. • Poseidon Criteria

5. Expected POR management
• Pituitary suppression regimens
• Type and dose of gonadotropins
• Natural cycle IVF/mild stimulation
• Dual stimulation
• Additional supplements
Androgens
Growth hormone
Antioxidants
Unexpected POR management
• Type of gonadotropins
• Type of downregulation protocol
• Increase of initial dose of stimulation
• Addition of rLH
• Dual stimulation
• Androgens supplementation

6. PRP
Embryo
Pooling
Duo- Stim
Medications

7. Androgen Effect on
Folliculogenesis
• Androgen receptors
 Expressed by all stages of
growing follicles
 Follicular fluid androgen
levels are positively
correlated to granulosa cell
androgen receptor and FSH
receptor expression
• Androgens –
 Promote follicular growth
 Accumulation and/or
responsiveness to
gonadotropins
 Improve ovarian response to
stimulation in assisted
reproduction

8. Role of DHEA
• Dehydroepiandrosterone (DHEA)
• Precursor of estradiol (E2) and testosterone (T)
• Originates from adrenal zona reticularis and from
ovarian theca cells
• Both estrogen and androgen are considered to be
required for normal follicular development and
fertility
• Dose – 75 mg/day for 3 months

12. Role of Testosterone
• Testosterone gel
• Increase in intrafollicular androgen
• Increases the number of FSH receptors
on granulosa cells
• Improved growth of follicles
• Better response to gonadotropins
• Dose – 1 gm of 1% Testosterone gel on
external side of thigh for 6 to 8 weeks

14. Role of Growth
hormone (GH)
• GH receptors expressed in ovarian
granulosa, theca cells, oocytes, cumulus
cells, mammary glands, placenta and
uterus
• GH raises ovarian sensitivity to FSH
• Regulates ovarian function
• Promotes follicular maturation
• Enhances proliferation of thecal
and granulosa cells
• Improves follicular development
• Dose – 3 to 4 IU from day 1 of ovarian
stimulation till HCG trigger

16. Role of
Coenzyme Q 10
• Known as Ubiquinone (antioxidant)
• Involved in electron transport in
mitochondrial respiratory chain and
oxidative phosphorylation to
produce ATP
• Restores oocyte mitochondrial
function and fertility during
reproductive ageing
• Dose – 300 to 600 mg /day

18. IVF
Protocols
for low
ovarian
reserve
Higher doses of
gonadotropins
he application of
recombinant FSH
(r FSH)
Luteal start of
FSH
The usage of LH
Adjunctive usage
of growth
hormone (GH)
The luteal
beginning of
GnRHa
Stop GnRHa
protocols
GnRH antagonists
programs (GnRH
– ant)
Organic cycle
Androgen
supplements
Use of letrozole
Lower HCG levels
in initial
stimulation

19. • Various Ovarian Stimulation Protocols

21. Duo- Stim

23. Ther Adv Reprod Health
2021, Vol. 15: 1–13
DOI: 10.1177/
26334941211024172
© The Author(s), 2021.
Article reuse guidelines:
sagepub.com/journals-
permissions
Therapeutic Advances in Reproductive Health
New insights into ART/IVF in Poor Ovarian Responders Special Collection
Double or dual stimulation in poor
ovarian responders: where do we stand?
Mehtap Polat, Sezcan Mumusoglu, Irem Yarali Ozbek, Gurkan Bozdag and Hakan Yarali
Abstract: Recent advances in our recognition of two to three follicular waves of development
in a single menstrual cycle has challenged the dogmatic approach of ovarian stimulation for
in vitro fertilization starting in the early follicular phase. First shown in veterinary medicine
and thereafter in women, luteal phase stimulation–derived oocytes are at least as competent
as those retrieved following follicular phase stimulation. Poor ovarian responders still remain
a challenge for many decades simply because they do not respond to ovarian stimulation.
Performing follicular phase stimulation and luteal phase stimulation in the same menstrual
cycle, named as double stimulation/dual stimulation, clearly increases the number of oocytes,
which is a robust surrogate marker of live birth rate in in vitro fertilization across all female
ages. Of interest, apart from one study, the bulk of evidence reports significantly higher
number of oocytes following luteal phase stimulation when compared with follicular phase
stimulation; hence, performing double stimulation/dual stimulation doubles the number
of oocytes leading to a marked decrease in patient drop-out rate which is one of the major
factors limiting cumulative live birth rates in such poor prognosis patients. The limited data
with double stimulation/dual stimulation-derived embryos is reassuring for obstetric and
neonatal outcome. The mandatory requirement of freeze-all and lack of cost-effectiveness
data are limitations of this novel approach. Double stimulation/dual stimulation is an effective
strategy when the need to obtain oocytes is urgent, including patients with malignant diseases
1024172reh0010.1177/26334941
211024172 therapeutic adv ancesin reproductiv ehealthm pola t, smumusoglu
review-ar ticle2021 2021
Review
Abstract: Recent advances in our recognition of two to three follicular waves of development
in a single menstrual cycle has challenged the dogmatic approach of ovarian stimulation for
in vitro fertilization starting in the early follicular phase. First shown in veterinary medicine
and thereafter in women, luteal phase stimulation–derived oocytes are at least as competent
as those retrieved following follicular phase stimulation. Poor ovarian responders still remain
a challenge for many decades simply because they do not respond to ovarian stimulation.
Performing follicular phase stimulation and luteal phase stimulation in the same menstrual
cycle, named as double stimulation/dual stimulation, clearly increases the number of oocytes,
which is a robust surrogate marker of live birth rate in in vitro fertilization across all female
ages. Of interest, apart from one study, the bulk of evidence reports significantly higher
number of oocytes following luteal phase stimulation when compared with follicular phase
stimulation; hence, performing double stimulation/dual stimulation doubles the number
of oocytes leading to a marked decrease in patient drop-out rate which is one of the major
factors limiting cumulative live birth rates in such poor prognosis patients. The limited data
with double stimulation/dual stimulation-derived embryos is reassuring for obstetric and
neonatal outcome. The mandatory requirement of freeze-all and lack of cost-effectiveness
data are limitations of this novel approach. Double stimulation/dual stimulation is an effective
strategy when the need to obtain oocytes is urgent, including patients with malignant diseases
undergoing oocyte cryopreservation and patients of advanced maternal age or with reduced
ovarian reserve.
Keywords: double stimulation, dual stimulation, number of oocytes, poor ovarian response

25. ShanghaiProtocol

28. Embryo Pooling

29. Our study suggests that in patients undergoing ICSI-PGD
who do not reach enough embryos in a single stimulation
cycle, pooling embryos from consecutive ovarian
stimulation cycles is a promising strategy, which can
render a cumulative pregnancy rate comparable to those
patients who only require one stimulation cycle.

31. Embryo Pooling @AFGC
0
5
10
15
20
25
30
35
40
EP1 EP2 EP3
Number
of
patients
Number of embryo pooling cycles

32. Platelet Rich Plasma (PRP)

33. Novel Insightsfrom Clinical Practice
Gynecol Obstet Invest
ACase Serieson Platelet-Rich Plasma
Revolutionary Management of Poor
Responder Patients
Konstantinos Sfakianoudisa Mara Simopouloub Nikolaos Nitsosa
Anna Rapanib Agni Pantoua Terpsithea Vaxevanogloua Georgia Kokkalia
Michael Koutsilierisb Konstantinos Pantosa
a
Centre for Human Reproduction,GenesisAthensClinic,Athens,Greece; b
Department of Physiology,Medical
School,National and Kapodistrian University of Athens,Athens,Greece
Received:February 4,2018
Accepted after revision:June 28,2018
Published online:August 22,2018
Established Facts
• Research on poor ovarian response(POR) patientsfailsto providean efficient treatment method.
• AutologousPlatelet-Rich Plasma(PRP) treatment hasalready been widely applied for numerousmed-
ical issueswithout complications.
Novel Insights
• In theabsenceof an overall efficient treatment protocol for poor responders, PRPtreatment could be
successfully employed asan alternativeeffectiveand safeapproach.
• Ovarian infusion of PRPcould improveovarian functionality.
DOI:10.1159/000491697
a
Centre for Human Reproduction,GenesisAthensClinic,Athens,Greece; b
Department of Physiology,Medical
School,National and Kapodistrian University of Athens,Athens,Greece
Established Facts
• Research on poor ovarian response(POR) patientsfailsto providean efficient treatment method.
• AutologousPlatelet-Rich Plasma(PRP) treatment hasalready been widely applied for numerousmed-
ical issueswithout complications.
Novel Insights
• In theabsenceof an overall efficient treatment protocol for poor responders, PRPtreatment could be
successfully employed asan alternativeeffectiveand safeapproach.
• Ovarian infusion of PRPcould improveovarian functionality.

34. Conclusion: Even though the treatment of POR responders remains as a
therapeutical challenge, the usage of intraovarian injection of autologous
PRP in PORs before the IVF performance brings a glimpse of new hope in
increasing the success of IVF defined by clinical pregnancy and LBRs.

35. Poor Responder @
AFGC
Counsel
Optimize outcome
Select Protocol
Duo Stim
Embryo Pooling
PRP

36. • CONCLUSION
• Poor Responders need to be treated case by case to optimize their
outcome
• Duo stim, Embryo pooling and PRP are some newer modalities
• Success rates are still very modest and there is still a long way to go…