GnRH agonist and antagonist protocols differ in their effects on the pituitary gland and ability to prevent ovarian hyperstimulation syndrome (OHSS). The GnRH agonist protocol causes an initial flare effect and hormonal withdrawal before gonadotropin administration, while the antagonist protocol has no flare effect and allows gonadotropin administration to be integrated into spontaneous and mild stimulation cycles. The antagonist protocol also prevents OHSS by blocking the LH surge and has a shorter duration of stimulation.
The document discusses using biomarkers such as AMH, AFC, and FSH to individualize ovarian stimulation protocols based on a patient's predicted ovarian response. It reviews the evidence on how these biomarkers work and their advantages and limitations. The document also provides guidance on how to interpret biomarker results and tailor stimulation dosing and medications, such as using GnRH antagonists or LH supplementation, based on a patient's biomarker levels and expected response.
MANAGEMENT OF POOR RESPONDERS IN IVF BY DR SHASHWAT JANIDR SHASHWAT JANI
This document discusses the management of poor responders to ovarian stimulation. It defines poor responders according to the Bologna criteria as having two of the following: advanced age, a previous poor response, or abnormal biomarkers of ovarian reserve. It identifies various risk factors for poor response and stresses the importance of predicting response before treatment. It then discusses individualized controlled ovarian stimulation, including increasing gonadotropin doses, modifying GnRH analog protocols, using GnRH antagonists, and supplementing with growth hormone, estradiol, recombinant LH, and androgens to potentially improve outcomes for poor responders.
The document discusses management strategies for poor responders undergoing assisted reproductive technology. It begins by defining poor responders according to the Bologna criteria and shows how live birth rates decrease significantly with fewer oocytes retrieved. It then outlines an approach to managing poor responders that includes identifying at-risk patients using biomarkers like AMH, individualizing controlled ovarian stimulation protocols, optimizing lab procedures, and tailoring embryo transfer. Specific strategies discussed include using gonadotropins like recombinant FSH, adding LH supplementation, antagonist protocols, and minimal stimulation approaches.
Is There a Best Stimulation Protocol in OI/IUI Cycles?Sandro Esteves
Individualized stimulation protocols maximize benefits and minimize risks in OI/IUI cycles. Biomarkers like AMH and AFC can help predict ovarian response. For CC stimulation, 50mg daily for 5 days is typically used for up to 3 cycles before considering injectables. Low-dose step-up gonadotropin stimulation starting at 37.5-50IU is effective with fewer risks than conventional protocols. Recombinant hormones provide similar outcomes to urinary products but with less impurities. Adding recombinant LH may benefit some patients, like those with low LH levels.
Ovarian reserve testing is important before planning IVF cycle, ovulation induction, family planning reasons, before and after chemotherapy and radiotherapy. Ovarian reserve testing such as AMH may help also in diagnosis of granulosa cell tumors and amenorrhea.
Management of poor ovarian reserve- Dr Parul KatiyarDr Parul Katiyar
Premature ovarian aging or ovarian failure is a major cause of female factor infertility. Dr Parul explains the mechanism of premature ovarian failure and discusses some simple measures to preserve/ regain fertility among women.
The document discusses changing protocols for in vitro fertilization (IVF) from gonadotropin-releasing hormone (GnRH) agonists to GnRH antagonists. Some key points discussed include:
1) GnRH antagonists are associated with a lower risk of ovarian hyperstimulation syndrome (OHSS) compared to GnRH agonists.
2) While efficacy outcomes like live birth and pregnancy rates are similar between the two protocols, GnRH antagonists require fewer gonadotropin ampoules and have a shorter duration of stimulation.
3) Based on multiple randomized controlled trials and meta-analyses, it is justified to shift from GnRH agonists to GnRH antagonists for IVF
The document discusses using biomarkers such as AMH, AFC, and FSH to individualize ovarian stimulation protocols based on a patient's predicted ovarian response. It reviews the evidence on how these biomarkers work and their advantages and limitations. The document also provides guidance on how to interpret biomarker results and tailor stimulation dosing and medications, such as using GnRH antagonists or LH supplementation, based on a patient's biomarker levels and expected response.
MANAGEMENT OF POOR RESPONDERS IN IVF BY DR SHASHWAT JANIDR SHASHWAT JANI
This document discusses the management of poor responders to ovarian stimulation. It defines poor responders according to the Bologna criteria as having two of the following: advanced age, a previous poor response, or abnormal biomarkers of ovarian reserve. It identifies various risk factors for poor response and stresses the importance of predicting response before treatment. It then discusses individualized controlled ovarian stimulation, including increasing gonadotropin doses, modifying GnRH analog protocols, using GnRH antagonists, and supplementing with growth hormone, estradiol, recombinant LH, and androgens to potentially improve outcomes for poor responders.
The document discusses management strategies for poor responders undergoing assisted reproductive technology. It begins by defining poor responders according to the Bologna criteria and shows how live birth rates decrease significantly with fewer oocytes retrieved. It then outlines an approach to managing poor responders that includes identifying at-risk patients using biomarkers like AMH, individualizing controlled ovarian stimulation protocols, optimizing lab procedures, and tailoring embryo transfer. Specific strategies discussed include using gonadotropins like recombinant FSH, adding LH supplementation, antagonist protocols, and minimal stimulation approaches.
Is There a Best Stimulation Protocol in OI/IUI Cycles?Sandro Esteves
Individualized stimulation protocols maximize benefits and minimize risks in OI/IUI cycles. Biomarkers like AMH and AFC can help predict ovarian response. For CC stimulation, 50mg daily for 5 days is typically used for up to 3 cycles before considering injectables. Low-dose step-up gonadotropin stimulation starting at 37.5-50IU is effective with fewer risks than conventional protocols. Recombinant hormones provide similar outcomes to urinary products but with less impurities. Adding recombinant LH may benefit some patients, like those with low LH levels.
Ovarian reserve testing is important before planning IVF cycle, ovulation induction, family planning reasons, before and after chemotherapy and radiotherapy. Ovarian reserve testing such as AMH may help also in diagnosis of granulosa cell tumors and amenorrhea.
Management of poor ovarian reserve- Dr Parul KatiyarDr Parul Katiyar
Premature ovarian aging or ovarian failure is a major cause of female factor infertility. Dr Parul explains the mechanism of premature ovarian failure and discusses some simple measures to preserve/ regain fertility among women.
The document discusses changing protocols for in vitro fertilization (IVF) from gonadotropin-releasing hormone (GnRH) agonists to GnRH antagonists. Some key points discussed include:
1) GnRH antagonists are associated with a lower risk of ovarian hyperstimulation syndrome (OHSS) compared to GnRH agonists.
2) While efficacy outcomes like live birth and pregnancy rates are similar between the two protocols, GnRH antagonists require fewer gonadotropin ampoules and have a shorter duration of stimulation.
3) Based on multiple randomized controlled trials and meta-analyses, it is justified to shift from GnRH agonists to GnRH antagonists for IVF
Role of adjuvants in poor ovarian responders , undergoing infertility treatment , in terms of Intra uterine inseminations ( IUI ) to In Vitro Fertilization ( IVF )
Improving Success by Tailoring Ovarian StimulationSandro Esteves
This document summarizes a presentation given by Dr. Sandro Esteves on improving IVF success through tailored ovarian stimulation. The presentation covered factors that determine ovarian response, strategies for high and poor responders, and evidence for different stimulation protocols. For high responders, low starting doses of rFSH, GnRH antagonists, and GnRH agonist triggering were recommended based on evidence from randomized controlled trials and observational studies. For poor responders, GnRH antagonists were suggested to potentially improve outcomes based on data from 14 RCTs.
The document summarizes a systematic review and meta-analysis that evaluated the efficacy of mild ovarian stimulation compared to conventional IVF in poor responder women undergoing IVF/ICSI treatment cycles. The analysis found that various modalities of mild ovarian stimulation resulted in comparable pregnancy rates, number of retrieved follicles, and cancellation rates, but with shorter duration of stimulation, compared to conventional IVF protocols. Therefore, the review concludes that mild ovarian stimulation could replace conventional IVF as a treatment option for poor responder women undergoing IVF/ICSI.
This document discusses poor ovarian response, which is defined as the failure to develop sufficient mature follicles following ovarian stimulation for IVF. Poor responders represent a heterogeneous group that can be divided into three categories based on age and hormonal profiles. Assessments of ovarian reserve like FSH, AMH, antral follicle count and CCCT help identify patients at risk. Treatment protocols aim to improve response through customized stimulation, LH supplementation, and adjuvants like DHEA, growth hormone, and anti-oxidants. Further research on tools like 3D Doppler and therapies like growth hormone may help optimize outcomes for poor responders.
This document discusses strategies for preventing severe ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization treatment. It describes the pathogenesis of OHSS and risk factors. Methods for prevention discussed include using a mild stimulation protocol, metformin treatment, coasting by withholding gonadotropins before triggering ovulation, using a GnRH antagonist protocol instead of agonist, cryopreserving all embryos, and administering intravenous albumin or hydroxyethyl starch after oocyte retrieval to reduce risk. The document concludes that OHSS is a preventable complication through various medical interventions and protocols.
Poor and hyper responders: biomarkers management, strategies
This document discusses the use of biomarkers such as AMH, AFC, and genetic markers to predict ovarian response and tailor IVF stimulation strategies. Key points:
1. AMH and AFC are effective at predicting poor and hyper ovarian response but not live birth rates. They are useful for choosing protocols.
2. Genetic markers of FSH and LH receptors can help explain hypo-sensitivity to FSH in some patients.
3. An integrated approach combining hormonal, functional and genetic biomarkers is needed to select the optimal treatment protocol for each patient.
4. Individualized treatment based on biomarkers can reduce cancellations, OHSS
Ovarian Reserve Testing in Infertility Dr. Jyoti Agarwal Dr. Sharda JainLifecare Centre
The Best Gametes
Give The Best Result
OVARIAN RESERVE
Plan fertility preservation
Fertility outcome
Response to ovarian stimulation
Predict pregnancy rate
Monitor fertility decline
Fertility after chemotherapy and cancer treatment
This document discusses the definition and management of poor responders in IVF treatment. It begins by outlining the ESHRE consensus definition of a poor responder as having two of three features: advanced maternal age, a previous poor response, or an abnormal ovarian reserve test. It then lists factors that can predict a poor response such as AFC, AMH, ovarian volume, and prior poor response. The document discusses precyle adjuvants like DHEA supplementation, cyst drainage, and oral contraceptives. It also reviews stimulation protocols including agonist versus antagonist, natural cycle IVF, and dosing intervals. Laboratory options for poor responders like ICSI, PGS, and embryo transfer timing are discussed. The role of donor
This document discusses methods for assessing ovarian reserve, which is a measure of female fertility that declines with age. It presents 8 methods for assessing ovarian reserve: 1) follicle stimulating hormone levels 2) estradiol levels 3) progesterone levels 4) inhibin B levels 5) anti-Mullerian hormone levels 6) antral follicle count 7) ovarian blood flow measurements 8) ovarian biopsy. It provides details on each method, including their clinical applications and limitations in assessing ovarian reserve.
AMH OVARIAN RESERVEMARKER Dr Jyoti Bhasker ,Dr. Sharda Jain Dr. Jyoti Ag...Lifecare Centre
This document summarizes markers of ovarian reserve and methods for testing ovarian reserve. It discusses how anti-Mullerian hormone (AMH) levels provide a better indicator of ovarian reserve than other markers, as AMH levels change least between cycles and are unaffected by other factors. AMH testing can help personalize infertility treatment by predicting response and tailoring stimulation protocols based on a patient's AMH level and ovarian reserve.
This document provides guidelines for stimulating patients undergoing IVF or ICSI treatment. It outlines the typical IVF/ICSI treatment steps including pituitary desensitization, controlled ovarian hyperstimulation with gonadotropins, triggering with hCG, oocyte retrieval, fertilization, embryo culture, embryo transfer, and luteal phase support. It then describes two common protocols - the GnRH antagonist and GnRH agonist protocols - and provides details on gonadotropin dosing and timing of administration. The document also provides recommendations on patient evaluation prior to treatment, ultrasound monitoring during stimulation, factors to consider when determining gonadotropin dose, and endometrial thickness goals.
Ovulation Induction in I.U.I. Dr. Sharda Jain Dr. Jyoti Agarwal Dr. Jyoti Bh...Lifecare Centre
Letrozole is an aromatase inhibitor that has been shown to be effective for ovulation induction. It works by decreasing estrogen production in the ovaries. Some advantages of letrozole over clomiphene citrate include shorter half-life, lack of anti-estrogenic effects on the endometrium and cervical mucus, increased uterine blood flow, and lower risks of multiple pregnancy and OHSS. Common side effects include hot flashes and headaches. Guidelines from several medical societies recommend letrozole as a first-line treatment for ovulation induction in women with PCOS. The starting dose is typically 2.5 mg daily for 5 days, but step-up protocols have also shown effectiveness.
This document discusses the use of letrozole for ovulation induction. It begins by explaining how letrozole works at a molecular level to stimulate follicular growth, noting key differences from clomiphene citrate such as not blocking estrogen receptors and maintaining feedback inhibition. Clinical studies are then summarized finding letrozole to have higher ovulation and live birth rates than clomiphene citrate, especially in women with PCOS or who are clomiphene citrate resistant. The document concludes by stating letrozole has been used successfully for ovulation induction in PCOS, intrauterine insemination, and ovarian stimulation for IVF/ICSI.
This document discusses the management of poor or hyper ovarian response in IVF treatment. It covers topics such as predicting ovarian reserve, definitions of poor response, protocols for poor and hyper responders, and techniques like coasting to help prevent ovarian hyperstimulation syndrome. Coasting, where gonadotropin administration is stopped but down regulation continued, is an effective way to prevent OHSS while still allowing for embryo retrieval and transfer. GnRH antagonist protocols may also help lower the risk of OHSS compared to long agonist protocols. There is no single best protocol, and treatments should be individualized based on patient factors and expectations.
The document discusses recent advances in controlled ovarian stimulation (COS) protocols for infertility treatment. It describes how recombinant gonadotropins are purer and safer than urinary gonadotropins, while having similar clinical efficacy. COS protocols now utilize GnRH antagonists to simplify treatment and decrease the risk of ovarian hyperstimulation syndrome compared to agonists. Overall, novel COS protocols incorporate recombinant gonadotropins and GnRH antagonists to provide patient-friendly stimulation with good outcomes.
Significant increase in live birth rate is found when IUI is done with stimulation compared with IUI in natural cycle in women with Unexplained Infertility .
The document discusses the definition and management of poor ovarian response. Poor response is generally defined as women with low ovarian reserve or a poor response to ovarian stimulation. As women age, their ovarian reserve declines resulting in fewer remaining eggs. The infertility specialist aims to assess biological age by measuring remaining egg count. Treatment options discussed include clomiphene citrate, letrozole, metformin, gonadotropins, ovarian drilling, and various IVF protocols tailored for poor responders. No single treatment guarantees success, and expectations must be managed through counseling.
Ovarian reserve refers to the reproductive potential left within a woman's two ovaries based on number and quality of eggs. Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of the remaining eggs
This document discusses various methods for ovarian stimulation in IVF treatment. It begins by describing the early history of IVF and the move away from using fertility medications to a more natural approach. It then outlines different protocols for ovarian stimulation preparation including natural cycles, minimal stimulation, in vitro maturation, and various FSH stimulation methods with and without agonists/antagonists. The majority of the document focuses on comparing the use of GnRH agonists versus antagonists, including their modes of action, individualization of protocols, studies comparing outcomes, and the ability of antagonists to reduce OHSS risk. It notes some problems with ovarian stimulation methods including costs, side effects, and long-term risks.
Women's ovarian reserve decreases with age, resulting in infertility around age 40-50. Ovarian reserve reflects the number and quality of eggs and can be assessed through markers like FSH, estradiol, AMH, antral follicle count, and ovarian volume. AMH levels provide the best predictor of ovarian reserve as they fluctuate less than FSH and correlate with antral follicle counts. Both low (<0.5 ng/mL) and high (>2.5 ng/mL) AMH levels impact fertility and IVF outcomes. AMH testing is recommended for women over 30, those with risk factors for low reserve, or who are undergoing fertility treatments.
Role of adjuvants in poor ovarian responders , undergoing infertility treatment , in terms of Intra uterine inseminations ( IUI ) to In Vitro Fertilization ( IVF )
Improving Success by Tailoring Ovarian StimulationSandro Esteves
This document summarizes a presentation given by Dr. Sandro Esteves on improving IVF success through tailored ovarian stimulation. The presentation covered factors that determine ovarian response, strategies for high and poor responders, and evidence for different stimulation protocols. For high responders, low starting doses of rFSH, GnRH antagonists, and GnRH agonist triggering were recommended based on evidence from randomized controlled trials and observational studies. For poor responders, GnRH antagonists were suggested to potentially improve outcomes based on data from 14 RCTs.
The document summarizes a systematic review and meta-analysis that evaluated the efficacy of mild ovarian stimulation compared to conventional IVF in poor responder women undergoing IVF/ICSI treatment cycles. The analysis found that various modalities of mild ovarian stimulation resulted in comparable pregnancy rates, number of retrieved follicles, and cancellation rates, but with shorter duration of stimulation, compared to conventional IVF protocols. Therefore, the review concludes that mild ovarian stimulation could replace conventional IVF as a treatment option for poor responder women undergoing IVF/ICSI.
This document discusses poor ovarian response, which is defined as the failure to develop sufficient mature follicles following ovarian stimulation for IVF. Poor responders represent a heterogeneous group that can be divided into three categories based on age and hormonal profiles. Assessments of ovarian reserve like FSH, AMH, antral follicle count and CCCT help identify patients at risk. Treatment protocols aim to improve response through customized stimulation, LH supplementation, and adjuvants like DHEA, growth hormone, and anti-oxidants. Further research on tools like 3D Doppler and therapies like growth hormone may help optimize outcomes for poor responders.
This document discusses strategies for preventing severe ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization treatment. It describes the pathogenesis of OHSS and risk factors. Methods for prevention discussed include using a mild stimulation protocol, metformin treatment, coasting by withholding gonadotropins before triggering ovulation, using a GnRH antagonist protocol instead of agonist, cryopreserving all embryos, and administering intravenous albumin or hydroxyethyl starch after oocyte retrieval to reduce risk. The document concludes that OHSS is a preventable complication through various medical interventions and protocols.
Poor and hyper responders: biomarkers management, strategies
This document discusses the use of biomarkers such as AMH, AFC, and genetic markers to predict ovarian response and tailor IVF stimulation strategies. Key points:
1. AMH and AFC are effective at predicting poor and hyper ovarian response but not live birth rates. They are useful for choosing protocols.
2. Genetic markers of FSH and LH receptors can help explain hypo-sensitivity to FSH in some patients.
3. An integrated approach combining hormonal, functional and genetic biomarkers is needed to select the optimal treatment protocol for each patient.
4. Individualized treatment based on biomarkers can reduce cancellations, OHSS
Ovarian Reserve Testing in Infertility Dr. Jyoti Agarwal Dr. Sharda JainLifecare Centre
The Best Gametes
Give The Best Result
OVARIAN RESERVE
Plan fertility preservation
Fertility outcome
Response to ovarian stimulation
Predict pregnancy rate
Monitor fertility decline
Fertility after chemotherapy and cancer treatment
This document discusses the definition and management of poor responders in IVF treatment. It begins by outlining the ESHRE consensus definition of a poor responder as having two of three features: advanced maternal age, a previous poor response, or an abnormal ovarian reserve test. It then lists factors that can predict a poor response such as AFC, AMH, ovarian volume, and prior poor response. The document discusses precyle adjuvants like DHEA supplementation, cyst drainage, and oral contraceptives. It also reviews stimulation protocols including agonist versus antagonist, natural cycle IVF, and dosing intervals. Laboratory options for poor responders like ICSI, PGS, and embryo transfer timing are discussed. The role of donor
This document discusses methods for assessing ovarian reserve, which is a measure of female fertility that declines with age. It presents 8 methods for assessing ovarian reserve: 1) follicle stimulating hormone levels 2) estradiol levels 3) progesterone levels 4) inhibin B levels 5) anti-Mullerian hormone levels 6) antral follicle count 7) ovarian blood flow measurements 8) ovarian biopsy. It provides details on each method, including their clinical applications and limitations in assessing ovarian reserve.
AMH OVARIAN RESERVEMARKER Dr Jyoti Bhasker ,Dr. Sharda Jain Dr. Jyoti Ag...Lifecare Centre
This document summarizes markers of ovarian reserve and methods for testing ovarian reserve. It discusses how anti-Mullerian hormone (AMH) levels provide a better indicator of ovarian reserve than other markers, as AMH levels change least between cycles and are unaffected by other factors. AMH testing can help personalize infertility treatment by predicting response and tailoring stimulation protocols based on a patient's AMH level and ovarian reserve.
This document provides guidelines for stimulating patients undergoing IVF or ICSI treatment. It outlines the typical IVF/ICSI treatment steps including pituitary desensitization, controlled ovarian hyperstimulation with gonadotropins, triggering with hCG, oocyte retrieval, fertilization, embryo culture, embryo transfer, and luteal phase support. It then describes two common protocols - the GnRH antagonist and GnRH agonist protocols - and provides details on gonadotropin dosing and timing of administration. The document also provides recommendations on patient evaluation prior to treatment, ultrasound monitoring during stimulation, factors to consider when determining gonadotropin dose, and endometrial thickness goals.
Ovulation Induction in I.U.I. Dr. Sharda Jain Dr. Jyoti Agarwal Dr. Jyoti Bh...Lifecare Centre
Letrozole is an aromatase inhibitor that has been shown to be effective for ovulation induction. It works by decreasing estrogen production in the ovaries. Some advantages of letrozole over clomiphene citrate include shorter half-life, lack of anti-estrogenic effects on the endometrium and cervical mucus, increased uterine blood flow, and lower risks of multiple pregnancy and OHSS. Common side effects include hot flashes and headaches. Guidelines from several medical societies recommend letrozole as a first-line treatment for ovulation induction in women with PCOS. The starting dose is typically 2.5 mg daily for 5 days, but step-up protocols have also shown effectiveness.
This document discusses the use of letrozole for ovulation induction. It begins by explaining how letrozole works at a molecular level to stimulate follicular growth, noting key differences from clomiphene citrate such as not blocking estrogen receptors and maintaining feedback inhibition. Clinical studies are then summarized finding letrozole to have higher ovulation and live birth rates than clomiphene citrate, especially in women with PCOS or who are clomiphene citrate resistant. The document concludes by stating letrozole has been used successfully for ovulation induction in PCOS, intrauterine insemination, and ovarian stimulation for IVF/ICSI.
This document discusses the management of poor or hyper ovarian response in IVF treatment. It covers topics such as predicting ovarian reserve, definitions of poor response, protocols for poor and hyper responders, and techniques like coasting to help prevent ovarian hyperstimulation syndrome. Coasting, where gonadotropin administration is stopped but down regulation continued, is an effective way to prevent OHSS while still allowing for embryo retrieval and transfer. GnRH antagonist protocols may also help lower the risk of OHSS compared to long agonist protocols. There is no single best protocol, and treatments should be individualized based on patient factors and expectations.
The document discusses recent advances in controlled ovarian stimulation (COS) protocols for infertility treatment. It describes how recombinant gonadotropins are purer and safer than urinary gonadotropins, while having similar clinical efficacy. COS protocols now utilize GnRH antagonists to simplify treatment and decrease the risk of ovarian hyperstimulation syndrome compared to agonists. Overall, novel COS protocols incorporate recombinant gonadotropins and GnRH antagonists to provide patient-friendly stimulation with good outcomes.
Significant increase in live birth rate is found when IUI is done with stimulation compared with IUI in natural cycle in women with Unexplained Infertility .
The document discusses the definition and management of poor ovarian response. Poor response is generally defined as women with low ovarian reserve or a poor response to ovarian stimulation. As women age, their ovarian reserve declines resulting in fewer remaining eggs. The infertility specialist aims to assess biological age by measuring remaining egg count. Treatment options discussed include clomiphene citrate, letrozole, metformin, gonadotropins, ovarian drilling, and various IVF protocols tailored for poor responders. No single treatment guarantees success, and expectations must be managed through counseling.
Ovarian reserve refers to the reproductive potential left within a woman's two ovaries based on number and quality of eggs. Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of the remaining eggs
This document discusses various methods for ovarian stimulation in IVF treatment. It begins by describing the early history of IVF and the move away from using fertility medications to a more natural approach. It then outlines different protocols for ovarian stimulation preparation including natural cycles, minimal stimulation, in vitro maturation, and various FSH stimulation methods with and without agonists/antagonists. The majority of the document focuses on comparing the use of GnRH agonists versus antagonists, including their modes of action, individualization of protocols, studies comparing outcomes, and the ability of antagonists to reduce OHSS risk. It notes some problems with ovarian stimulation methods including costs, side effects, and long-term risks.
Women's ovarian reserve decreases with age, resulting in infertility around age 40-50. Ovarian reserve reflects the number and quality of eggs and can be assessed through markers like FSH, estradiol, AMH, antral follicle count, and ovarian volume. AMH levels provide the best predictor of ovarian reserve as they fluctuate less than FSH and correlate with antral follicle counts. Both low (<0.5 ng/mL) and high (>2.5 ng/mL) AMH levels impact fertility and IVF outcomes. AMH testing is recommended for women over 30, those with risk factors for low reserve, or who are undergoing fertility treatments.
R lh supplementation to rfsh in gnrh antagonist cyclesAlfredo Nazzaro
1) The study compared the effects of recombinant FSH (rFSH) supplementation alone versus rFSH supplemented with recombinant LH (rLH) in GnRH antagonist cycles on implantation and pregnancy rates.
2) They found that the rFSH + rLH group had higher numbers of retrieved and metaphase II oocytes, higher fertilization rates, and more grade I-II embryos compared to the rFSH only group.
3) The rFSH + rLH group also had higher implantation and clinical pregnancy rates. The authors conclude that rLH supplementation improves outcomes likely by enhancing oocyte quality and endometrial receptivity.
This document discusses optimizing treatment outcomes in assisted reproductive technology (ART). It begins with an outline of predictors of pregnancy in IVF and individualizing controlled ovarian stimulation (COS). The author then discusses evidence that the optimal number of oocytes retrieved is around 15 to maximize live birth rates. Strategies are presented for tailoring COS to individual phenotypes, including using biomarkers like AMH to predict response and adjusting gonadotropin preparations and protocols. Evidence is provided for approaches to optimize COS in both high and poor responders, such as using GnRH antagonists and LH supplementation respectively.
The document summarizes the evolution and implementation of reproductive synchronization protocols for cattle from the 1980s to present day. Key developments include:
1) The approval of prostaglandin drugs like Lutalyse in 1979 which allowed for manipulation of luteal function
2) Early synchronization protocols in the 1980s like the Targeted Breeding System which achieved 46% conception rates
3) Discovery of follicular waves in cattle in the 1980s which improved understanding of ovarian function
4) Publication of the Ovsynch protocol in 1995 which involved GnRH and PGF2α injections achieving high pregnancy rates
5) Addition of a presynchronization period before Ovsynch in 2001 which further increased conception rates
Individualizing Ovarian Stimulation Protocols for IVFSherInstitute
This document discusses embryo development and factors that influence IVF outcomes. It summarizes key stages of embryo development from fertilization through blastocyst formation. It identifies the woman's age, controlled ovarian stimulation protocol, and embryology laboratory as factors governing embryo aneuploidy and IVF success. The document provides details on different ovarian stimulation protocols and considerations for individual patient factors like ovarian reserve, previous response, and risk of over or underresponse.
This document provides information on suppositories, including their uses, advantages, challenges, and formulation considerations. Suppositories can be used to deliver drugs locally or systemically when oral administration is not possible. They melt or dissolve at body temperature for drug release and absorption. The document discusses important properties of suppository bases like cocoa butter and synthetic triglycerides, as well as factors that influence drug release and absorption from suppositories. It also provides details on the anatomy and physiology of the rectum relevant to suppository administration.
GnRH Antagonists in Controlled Ovarian StimulationSandro Esteves
This document provides an overview of a lecture on LH suppression in controlled ovarian hyperstimulation (COH) using GnRH antagonists. The key points covered include:
1) The importance of LH suppression in COH to prevent premature luteinization and improve outcomes.
2) How GnRH antagonists can be used for LH suppression compared to agonists. Clinical trials show antagonists reduce OHSS risk and duration of stimulation compared to agonists without impacting live birth rates.
3) Flexible or fixed antagonist protocols, use of oral contraceptives, and timing of hCG administration do not significantly impact outcomes. LH supplementation is generally not needed.
This document discusses gonadotropin-releasing hormone (GnRH) agonists and antagonists. It describes how GnRH agonists initially stimulate gonadotropin secretion but then cause desensitization of GnRH receptors, while GnRH antagonists immediately block gonadotropin secretion. Several GnRH agonists and antagonists are reviewed in terms of their mechanisms of action, pharmacokinetics, clinical uses and side effects. Key clinical uses of GnRH agonists and antagonists include fertility control, treatment of uterine fibroids, endometriosis, and prostate cancer.
This document discusses the role of LH in human reproduction and LH supplementation during ovarian stimulation for IVF. It provides evidence that LH supplementation is beneficial for certain patient subgroups, including older women over 35, poor responders, and patients with deeply suppressed endogenous LH levels. The rationale is that LH increases androgen production and has direct effects on the ovary that can improve outcomes for these groups.
PANEL DISCUSSION MANAGEMENT OF PCOS WOMB to TOMB . PANELISTS : Dr.Chitra...Lifecare Centre
This document summarizes a panel discussion on the management of polycystic ovarian syndrome (PCOS) from womb to tomb. The panel was moderated by Dr. Sharda Jain and included several specialists. PCOS has a continuum from early pre-pubertal years through menopause. Common symptoms in adolescents include menstrual irregularity, hyperandrogenism, acne, and hirsutism. Menstrual irregularity needs treatment to reduce endometrial cancer risk. Diagnosis involves evaluating hormones, blood sugar, and polycystic ovaries on ultrasound. Treatment focuses on managing clinical symptoms specific to each patient.
This document discusses strategies for managing patients with poor ovarian reserve or polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). It recommends testing ovarian reserve with antral follicle count (AFC), anti-Mullerian hormone (AMH) and past response history. Treatment options include increasing gonadotropins or using a mini-IVF/natural cycle approach. For poor responders, empiric therapies like acupuncture or supplements like DHEA may help improve reserve before using a letrozole/gonadotropin protocol. Managing expectations and discussing alternative options like donor eggs is important to avoid false hope or wasting money. Preventing ovarian hyperstimulation syndrome in P
GnRH agonist versus antagonist and impact on cycle outcomeSandro Esteves
This document summarizes a lecture on using GnRH agonists versus antagonists in ICSI cycles and the impact on cycle outcomes. It discusses that LH suppression is desirable in controlled ovarian stimulation to prevent premature ovulation and luteinization. While GnRH agonists were initially used for this starting in 1984, GnRH antagonists introduced in 1999 provide LH suppression without an initial flare effect and allow for a flexible treatment protocol. The summary reviews the findings that GnRH antagonists have no negative impact on estradiol levels, endometrial receptivity, or cycle parameters compared to agonists and provide a better safety profile with shorter treatment duration.
1) The document discusses the evolution of using GnRH antagonists in IVF treatment instead of agonists. Antagonists allow for a shorter, less invasive treatment with fewer injections and side effects like ovarian hyperstimulation syndrome (OHSS).
2) Clinical trials and Cochrane reviews have found antagonist protocols to be as effective as agonist protocols with comparable live birth rates but significantly reduced risk of OHSS. This makes antagonists the preferred protocol especially for high risk groups like PCOS patients.
3) The antagonist approach creates a safer, less stressful IVF experience for patients and allows treatments that were not possible with agonists, such as protocols for cancer patients needing immediate fertility preservation. The document predicts antagonists
Progesterone for luteal phase support in IVF cyclesHesham Al-Inany
Luteal phase support is essential for IVF cycles. Progesterone has many forms and modalities: which to use? this talk is an attempt to answer this question
This presentation discusses controlled ovarian hyperstimulation (COH) for patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). COH is challenging for PCOS patients due to an initial poor response followed by an exaggerated response, putting them at high risk for ovarian hyperstimulation syndrome (OHSS). The presentation recommends individualizing COH protocols based on a patient's risk factors to optimize egg retrieval while avoiding OHSS complications. GnRH antagonist protocols are preferred over agonists as they allow for GnRH agonist triggering to prevent OHSS in high responders. Careful monitoring and strategies like coasting or cryopreservation can further reduce OHSS risks for PCOS patients undergoing CO
Novel treatments to trigger final follicular maturation and luteal phase supportSandro Esteves
This document summarizes novel strategies for triggering final follicular maturation and supporting the luteal phase in fertility treatments. It discusses evaluating the quality of trigger and luteal phase support methods based on indicators of safety, effectiveness, and patient-centeredness. Specific strategies used at Androfert clinic are presented, including individualizing triggers and support according to patient risk factors. Recombinant hCG is shown to have advantages over urinary hCG in terms of effectiveness, safety, and patient preferences. GnRH agonist triggering avoids risk of ovarian hyperstimulation syndrome but needs additional luteal phase support.
Poor and hyper responders: biomarkers management, strategies
This document discusses the use of biomarkers such as AMH, AFC, and genetic markers to predict ovarian response and tailor IVF stimulation strategies. Key points:
1. AMH and AFC are effective at predicting poor and hyper ovarian response but not sufficient for live birth counseling.
2. Biomarkers can help choose protocols, such as using GnRH antagonists for normal responders and agonists to avoid OHSS in high responders.
3. An integrated approach considering hormonal, functional, and genetic biomarkers is needed to determine the optimal treatment strategy for each patient. FSH dose and potential LH supplementation should account for genetic
The document discusses the evolution of ovarian stimulation for assisted reproductive technology (ART). It covers:
1. The historical development of gonadotropins from early urinary extracts to modern recombinant products, which provide higher purity and consistency.
2. Key factors that affect IVF success and ovarian response to stimulation, including age, ovarian reserve markers like AMH and AFC, and individual patient characteristics.
3. New strategies for individualizing controlled ovarian stimulation (COS) protocols using recombinant gonadotropins, including lower starting doses, dose adjustments, and exploring flexibility in GnRH antagonist protocols.
The document discusses various tests used to assess ovarian reserve. It describes anti-Mullerian hormone (AMH) as the most sensitive marker that declines with age and correlates with antral follicle count (AFC). Basal follicle-stimulating hormone (FSH) levels increase with declining reserve but have inter-cycle variability. AFC counts the number of antral follicles and correlates with ovarian response, though cut-offs vary. No single test can reliably predict fertility or treatment response on its own.
Number of oocytes and progesterone levels in IVF: Do they matter?Sandro Esteves
- The document summarizes research on factors that influence IVF success rates, including the number of oocytes retrieved and progesterone levels.
- It finds that retrieving around 15 oocytes optimizes live birth rates, and that recombinant FSH preparations yield more oocytes than other gonadotropins.
- While progesterone levels on the day of hCG administration correlate with the number of oocytes, there is no clear evidence that certain progesterone levels negatively impact pregnancy rates, especially with adequate embryos for freezing and future transfers.
- Considering cumulative live birth rates from multiple transfer cycles is important to properly assess IVF success rates and outcomes. Optimizing oocyte yield, embryo culture, vitrification techniques, and performing
Optimize oocyte yield to maximize live birth in ARTSandro Esteves
This document discusses strategies for optimizing ovarian response in ART to maximize live birth rates. It introduces the POSEIDON criteria for stratifying "low prognosis" ART patients based on age, ovarian reserve markers, and number of oocytes retrieved. The target is to retrieve over 15 oocytes to maximize cumulative live birth rates. Personalized gonadotropin protocols and adjuvant therapies can be used to optimize response based on POSEIDON stratification. This includes starting dose, supplementation with LH, and dual stimulation if needed to obtain the estimated number of oocytes for at least one euploid embryo transfer.
OVARIAN RESERVE DIAGNOSIS & MANAGEMENT DR Sharda Jain Lifecare Centre
Diminished ovarian reserve is the loss of normal reproductive potential in the ovaries due to a lower count or quality of remaining eggs. It can be caused by factors like advanced age, chemotherapy, genetics, and lifestyle. Ovarian reserve tests assess markers like antral follicle count, anti-Mullerian hormone, and follicle-stimulating hormone to predict ovarian response. A combination of biochemical tests is effective for predicting diminished ovarian reserve. When test results indicate poor ovarian reserve, treatment options include protocols using gonadotropins, letrozole, or dehydroepiandrosterone to potentially increase live birth rates from in vitro fertilization.
This document discusses management strategies for poor responders undergoing assisted reproductive technology. It begins by defining poor responders according to the Bologna criteria. It then reviews biomarkers for predicting poor response, finding AMH and AFC to be similarly accurate. The document outlines an individualized approach to controlled ovarian stimulation for poor responders, discussing adjuvant therapies like growth hormone and testosterone. It reviews evidence that recombinant FSH preparations retrieve more oocytes than urinary FSH or HMG. GnRH antagonists may shorten stimulation duration slightly. LH supplementation, specifically recombinant LH added to FSH, may modestly improve pregnancy rates.
Anti-Mullerian Hormone (AMH) -Novel Biomarker & its ApplicationsDr. Rajesh Bendre
Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show ovarian reserve decline.
This document discusses poor responders in IVF treatment. It defines poor responders based on the Bologna criteria as women aged 40 or older, or with another risk factor, who have produced 3 or fewer oocytes in a conventional stimulation protocol or have an abnormal ovarian reserve test. The document discusses using lower gonadotropin doses (150-450 IU) for poor responders to reduce risks while still achieving pregnancy. It also analyzes the use of long agonist versus antagonist protocols, finding the long agonist protocol may increase maturity and lower cancellation rates for expected poor responders. Finally, it presents a study showing double stimulation protocols over 4 weeks can produce twice as many oocytes and blastocysts for poor
The document discusses monitoring stimulation of ovarian function during in vitro fertilization treatment. It summarizes that monitoring helps physicians choose the best treatment protocol and avoid complications, while also increasing medical knowledge. Specific monitoring aspects covered include the patient's initial parameters, ovarian response, and treatment completion. Three key goals of monitoring are increasing patient comfort, avoiding ovarian hyperstimulation syndrome, and reducing multiple pregnancy rates.
The document discusses monitoring stimulation of ovarian function during infertility treatments. It summarizes that monitoring helps physicians choose the best treatment protocol and avoid complications, while also increasing medical knowledge. Close monitoring of patient parameters, ovarian response, and treatment completion is described. The risks of multiple pregnancies are discussed, as well as efforts to reduce those risks through individualized treatment and using new technologies.
The document discusses monitoring stimulation of ovarian function during in vitro fertilization treatment. Monitoring helps physicians choose the best treatment protocol and avoid complications while increasing knowledge. It allows for patient comfort, prevents ovarian hyperstimulation syndrome, and reduces multiple pregnancies. Endometrial thickness measured by ultrasound can predict pituitary suppression and be used to monitor treatment instead of estrogen level tests. Aspiration of ovarian cysts seen on ultrasound leads to acute decreases in estrogen levels and endometrial thickness.
Free Information Session 5th September 2012: Recent Breakthroughs in IVFFertility SA
This document summarizes new directions in in vitro fertilization (IVF) being explored at FertilitySA to address common problems experienced by couples. These include using growth hormone to increase egg yield for those with low ovarian reserve, selecting sperm for ICSI based on hyaluron receptors, preimplantation genetic testing to identify genetic problems, endometrial biopsies to improve implantation, and culturing embryos in media containing GM-CSF to help with recurrent miscarriage. Ongoing trials are exploring the use of corifollitropin alfa to reduce injections and improve outcomes. The overall aim is to continue improving treatment through research and providing individualized care.
This document discusses discordance between FSH and AMH levels in predicting ovarian reserve and IVF outcomes. It notes that while both markers predict ovarian reserve, they do so at different stages of follicular development. Discrepancies between FSH and AMH levels occur in 20-43% of IVF cycles and can make predicting stimulation needs and outcomes difficult. Several studies found that when FSH and AMH levels disagreed, normal AMH predicted better outcomes like oocyte yield and live birth rates compared to normal FSH. The conclusion is that while both markers provide information, AMH appears to be a stronger predictor of cycle success when levels are discordant. Considering additional factors is needed to most accurately predict IVF success rates
This document summarizes several adjunct techniques used in IVF laboratories including sperm DNA fragmentation testing, advanced sperm selection methods like IMSI and pICSI, embryo selection techniques like time-lapse imaging and PGS, and mitochondrial DNA load measurement. It reviews the current evidence for each technique, noting that while some like TL imaging show promise, the evidence is still limited and inconclusive for many techniques to recommend their routine use to improve IVF outcomes. Larger randomized controlled trials are still needed to prove effectiveness.
Adjuvant therapy, also known as adjunct therapy or add-on therapy, is therapy given in addition to the primary or initial therapy to maximize its effectiveness.
Add-ons have become ubiquitous with the process of assisted reproduction (ART) which is markedly more complex than it was at its inception.
Similar to Individualization of Patient Treatment (20)
Oocyte number, female and male age, and ART outcomes Sandro Esteves
This document summarizes Sandro Esteves' presentation on optimizing ART success through individualizing oocyte retrieval targets based on a patient's age and ovarian reserve. It discusses:
1) The decline in blastocyst euploidy rates with increasing female age and the importance of oocyte quantity and quality for ART success.
2) The Poseidon criteria for stratifying "low prognosis" ART patients based on age and expected oocyte yield.
3) A mathematical model developed to estimate the minimum number of oocytes needed to achieve at least one euploid blastocyst based on a patient's age.
4) How individualizing treatment based on this oocyte target number can maximize ART efficiency
Luteal Phase Support: Key Variables to Achieve Success in ARTSandro Esteves
This document discusses luteal phase support in assisted reproductive technology cycles. It covers:
1. The pathophysiology of the luteal phase defect in stimulated cycles and the role of progesterone supplementation.
2. Different luteal phase support protocols after hCG trigger in fresh embryo transfer cycles, including progesterone alone versus progesterone plus hCG or GnRH agonist.
3. Luteal phase support considerations for frozen embryo transfer cycles, including the type and timing of estrogen and progesterone administration.
Understanding Strategies to Maximize Cumulative Live Birth RateSandro Esteves
1. The document discusses strategies for maximizing success in assisted reproductive technology (ART) treatment by stratifying patients based on factors that influence prognosis, such as age, ovarian reserve markers, and previous response to ovarian stimulation.
2. It introduces the Poseidon criteria for stratifying patients into four groups based on their predicted prognosis: two groups include younger or older patients with a previously suboptimal response, and two groups include those with expected poor ovarian reserve.
3. Stratifying patients according to factors of both oocyte quantity and quality allows for a more individualized treatment approach aimed at obtaining the estimated number of oocytes needed for achieving at least one euploid embryo transfer for each patient.
Role of LH in Controlled Ovarian StimulationSandro Esteves
1) The document discusses the role of LH in controlled ovarian hyperstimulation (COH). It notes that LH plays important roles in folliculogenesis and steroidogenesis.
2) It reviews rationales for LH supplementation in COH, such as lower endogenous LH levels and impaired steroidogenesis in certain patient groups.
3) Studies show LH supplementation can improve outcomes for poor responders and older patients, though effects may depend on the patient subgroup and study design. More research is still needed to determine which specific patient populations benefit most.
Air quality: is it that important? And if so, how to measure and control it?Sandro Esteves
Quality and Risk Management in the IVF Laboratory; Redlara Brasil, Belo Horizonte, 14-15 September 2016
Content:
1.Air quality: is it that important?
2. How to control?
3. How to measure?
Técnicas de Obtencão de Espermatozóides na Azoospermia - Como fazer?Sandro Esteves
This document discusses different techniques for obtaining sperm from men with azoospermia, including:
1) PESA, MESA, TESA, TESE, and Micro-TESE which are used to retrieve sperm from the epididymis or testicles.
2) Micro-TESE has higher sperm retrieval rates compared to conventional TESE, especially for men with non-obstructive azoospermia.
3) Sperm retrieved through Micro-TESE also has higher fertilization rates and live birth rates compared to TESE or techniques for obstructive azoospermia.
O documento discute varicocele e infertilidade masculina. Resume que:
1) Varicocele é causa comum de infertilidade masculina, associada a deterioração dos parâmetros seminais e função testicular;
2) A fisiopatologia envolve hipertermia, hipóxia e estresse oxidativo testicular devido ao refluxo venoso;
3) O tratamento da varicocele, seja cirúrgico ou por embolização, melhora os parâmetros seminais e fertilidade em muitos casos.
1. O documento discute como realizar uma revisão de artigos científicos de forma objetiva e construtiva.
2. São apresentados os objetivos da revisão por pares, as responsabilidades do revisor e dicas sobre como escrever comentários para o editor e autores.
3. O documento fornece diretrizes detalhadas para que os revisores avaliem com qualidade os artigos submetidos prestando um serviço útil aos editores e autores.
Este documento discute conceitos estatísticos importantes para a condução de pesquisas, como poder amostral, escolha do teste estatístico correto, intervalo de confiança e cálculo do tamanho amostral. O documento enfatiza que é crucial escolher o teste estatístico apropriado para o tipo de dados, evitar erros tipo I e II, e justificar o tamanho da amostra utilizada para validar conclusões.
Novel concepts in male factor infertility: clinical and laboratory perspectivesSandro Esteves
Presentation Objectives:
1. Update on the WHO reference values for semen parameters, and understand the role of sperm DNA fragmentation testing to decision-making strategies;
2. Learn how to counsel azoospermic men seeking fertility, and the role of gonadotropin therapy in this infertility condition;
3. Understand the benefits of microsurgery to both sperm retrieval and varicocele treatment;
4. Appraise the role of medical and surgical interventions to infertile men undergoing ART.
Public lecture - Stem Cell and Male InfertilitySandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Public Lecture - Stem Cell and Male Infertility
Clinical management of men with nonobstructive azoospermia - Role of IVF Labo...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 5: Role of IVF Laboratory in Nonobstructive Azoospermia
Clinical management of men with nonobstructive azoospermia - Sperm Retrieval ...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 4: Sperm Retrieval Methods in Nonobstructive Azoospermia
Clinical management of men with nonobstructive azoospermia - Steps Before Spe...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 3: Steps Before Sperm Retrieval in Nonobstructive Azoospermia
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfRahul Sen
Time-lapse embryo monitoring is an advanced imaging technique used in IVF to continuously observe embryo development. It captures high-resolution images at regular intervals, allowing embryologists to select the most viable embryos for transfer based on detailed growth patterns. This technology enhances embryo selection, potentially increasing pregnancy success rates.
Travel Clinic Cardiff: Health Advice for International TravelersNX Healthcare
Travel Clinic Cardiff offers comprehensive travel health services, including vaccinations, travel advice, and preventive care for international travelers. Our expert team ensures you are well-prepared and protected for your journey, providing personalized consultations tailored to your destination. Conveniently located in Cardiff, we help you travel with confidence and peace of mind. Visit us: www.nxhealthcare.co.uk
How to Control Your Asthma Tips by gokuldas hospital.Gokuldas Hospital
Respiratory issues like asthma are the most sensitive issue that is affecting millions worldwide. It hampers the daily activities leaving the body tired and breathless.
The key to a good grip on asthma is proper knowledge and management strategies. Understanding the patient-specific symptoms and carving out an effective treatment likewise is the best way to keep asthma under control.
Co-Chairs, Val J. Lowe, MD, and Cyrus A. Raji, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/AAPA activity titled “Alzheimer’s Disease Case Conference: Gearing Up for the Expanding Role of Neuroradiology in Diagnosis and Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/3PvVY25. CME/AAPA credit will be available until June 28, 2025.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
1. Jordan, Lebanon, Kuwait, Qatar, Bahrain – Nov 2012
Individualization of Patient
Treatment
Sandro Esteves, M.D., Ph.D.
Director, ANDROFERT
Center for Male Reproduction & Infertility
Campinas, BRAZIL
2. What is in it for me?
Use of Biomarkers to Individualize Ovarian
Stimulation Protocols
Recent Advances in Injectable Gonadotropins
Preparations
Rec-FSH vs Urinary Products
Agonist versus Antagonist GnRH
To whom to give rec-hLH? Differences between
rec-hLH and LH Activity in HMG Preparations?
Strategies to Improve Ovarian Stimulation
Best Protocols to Minimize Risks and Reduce
Dropout Rates in IVF and IUI/OI
Esteves, 2
3. Level of
evidence
Individualization of Patient Treatment
Lecture Structure
Points I Consider Highly Relevant in Clinical Practice;
Arguments Supported by Studies with High Level of Evidence.
Level Type of evidence
1a Obtained from meta-analysis of randomised trials
1b Obtained from at least one randomised trial
2a Obtained from one well-designed controlled study without
randomisation
2b Obtained from at least one other type of well-designed quasi-
experimental study
3 Obtained from well-designed non-experimental studies
(comparative and correlation studies, case series)
4 Obtained from expert committee reports or opinions or clinical
experience of respected authorities
Esteves, 3 Modified from Sackett et al. Oxford Centre for EBM Levels of Evidence (2009)
4. Individualization of Patient
Treatment
Esteves, SC – Nov 2012
Review this Lecture at:
http://www.androfert.com.br/review
Esteves, 4
5. What is in it for me?
Use of Biomarkers to Individualize Ovarian
Stimulation Protocols
Recent Advances in Gonadotropins Preparations
Rec-FSH vs urinary products
GnRH Agonist versus Antagonist
To whom to give rec-hLH? Differences between rec-
hLH and LH activity in HMG preparations?
Strategies to Improve Ovarian Stimulation
Best Protocols to Minimize Risks and Reduce Dropout
Rates in IVF
Esteves, 5
6. Central
Paradigm
Maximize Minimize
beneficial effects complications
of treatment and risks
High-quality Cycle cancellation,
oocyte yield OHSS, multiple
pregnancy
Fauser BC et al: Predictors of ovarian response: progress towards individualized treatment in ovulation
Esteves, 6 induction and ovarian stimulation. Hum Reprod Update 2008;14:1-14.
7. Factors Determining Response
to Ovarian Stimulation
Demographics and
anthropometrics (Age,
BMI, Race)
Genetic profile
Cause of Infertility
Years of Infertility
Health status
Nutritional status
Esteves, 7
8. Level
1a
Female Age Negative
Duration of infertility Predictors
Basal FSH
Type of infertility All reflecting
Indication ovarian
reserve
Fertilization method
Number of oocytes retrieved Positive
Number of embryos transferred Predictor
Embryo quality
Esteves, 8 van Loendersloot et al. Hum Reprod Update 2010; 16: 577–589.
9. Level
1a Use of Markers Pregnancy by number of oocytes
retrieved after mild (♦ ) or conventional
to Determine ( ) ovarian stimulation for IVF
Ovarian Reserve
⑤
Age ⑩
Biomarkers
● Hormonal Biomarkers
FSH, Inhibin-B, AMH
● Functional Biomarkers
Antral Follicle Count (AFC)
● Genetic Biomarkers
Single Nucleotide Polymorphisms
for FSH-R/LH/LH-R/E2-R/AMH-R
Verberg M et al. Hum Reprod Update 2009;15:5-12
Esteves, 9
10. Level
1a
AMH = AFC >Inhibin B >FSH >Age
Predictor
of Poor
Predictor of Excessive Response Response
● AFC studies
AMH Studies
Predictor of
Pregnancy
In ART
● AFC studies
AMH Studies
Broer et al. Hum Reprod Update 2011
Esteves, 10
Broer et al. Fertil Steril 2009
11. = remaining population of primordial and
resting follicles
Anti-Mullerian
Hormone levels
are correlated
with the
number of
follicles at
gonadotropin
independent
stage.
Esteves, 11
La Marca et al. Hum Reprod 2009
12. Level
1b Antral Follicle Count (AFC)
AFC alone on day 3 as a tool for
predicting the number of retrieved
oocytes in COS
= Number of antral
follicles present in
the ovaries at a given
time that can be
stimulated into
dominant follicle
growth by exogenous
Eldar-Geva et al. Fertil Steril 2005 gonadotropins
Esteves, 12 Devroey et al. Hum Reprod Update 2009
13. AMH and AFC
Anti-Mullerian Antral
Hormone Follicle
(ng/mL) Count
Cycle independent test; Simple and
Advantages
Intercycle stability inexpensive
Variation in test
No international assay interpretation and
standards for standardization;
Limitations
measurements (DSL & Moderate intercycle
Immunotech-Beckman) and interobserver
variability
Alviggi et al, Reprod Biol Endocrinol 2012; Broer et al, Hum Reprod Update 2011; Broekmans et al,
Fertil Steril 2009; Broer et al, Fertil Steril 2009; van Disseldorp et al, Hum Reprod 2010, La Marca
Esteves, 13 et al, Hum Reprod 2006; Hansen et al, Fertil Steril 2003; Elter et al, Gynecol Endocrinol 2005.
14. Markers of Ovarian Response
Antral Follicle Count (AFC)
Use a systematic process for counting antral follicles:
1. Identify the ovary.
Practical
2. Explore the dimensions in two planes (perform a scout sweep).
Recommendations for
3. Decide on the direction of the sweep to measure and count follicles.
Better Standardization:
● Cycle day 2-4
4. Measure the largest follicle in two dimensions.
A. If the largest follicle is ≤10 mm in diameter:
• Start to count from outer ovarian margin of the sweep to the
opposite margin. ● Count all AF 2-10mm
• Consider every round or oval transonic structure within the
ovarian margins to be a follicle. ● Real-time 2 dimension
• Repeat the procedure with the contralateral ovary. image adequate
• Combine the number of follicles in each ovary to obtain the AFC.
B. If the largest follicle is >10 mm in diameter: ● Transvaginal probe 7Mhz
• Further ascertain the size range of the follicles by measuring
each sequentially smaller follicle, in turn, until a follicle with a minimum
diameter of %10 mm is found.
• Perform a total count (as described) regardless of follicle
diameter.
• Subtract the number of follicles of >10 mm from the total follicle
count.
Esteves, 14
Broekmans et al., Fertil Steril, 2010; 94(3):1044-51
15. Use of Biomarkers to Individualize
Ovarian Stimulation Protocols
COS should maximize treatment beneficial effects
(high-quality oocyte yield) and minimize risks
(cancellation, OHSS, multiple pregnancy).
Significant predictive factors for pregnancy in IVF
are related to ovarian reserve.
AMH levels and AFC accurately determine
ovarian reserve. Results can be used to guide the
choice of COS protocols.
Both AMH and AFC have similar high accuracy to
predict which patients are at risk of excessive and
poor response to OS but should not be used to
predict the chances of pregnancy success.
Esteves, 15
16. What is in it for me?
Use of Biomarkers to Individualize Ovarian
Stimulation Protocols
Recent Advances in Injectable Gonadotropins
Preparations
Rec-hFSH vs Urinary products
GnRH Agonist versus Antagonist
To whom to give rec-hLH? Differences between rec-hLH
and LH activity in HMG preparations?
Strategies to Improve Ovarian Stimulation
Best Protocols to Minimize Risks and Reduce Dropout
Rates in IVF
Esteves, 16
17. • Incidence of Infertility (WHO II)
64%
• Prevalence of Infertile Patients
(WHO II) with PCO in Clinical
68% Practice
OI, IUI, IVF
Clomiphene Citrate
1st line in up to 56% of cases
Shift after an average of 3 cycles
Injectable Gonadotropins
Esteves, 17 Reproductive Hormones Report - GCC Countries (Feb 2011)
18. Long-
r-hFSH r-hFSH acting
+r-hLH r-hFSH
u-FSH HP FbM
FbM
Pituitary r-hFSH
u-FSH
FSH
u-hMG
Horse Puriity
PMSG and
Safety, Quality,
Specific
Consistency and Patient
Activity
Convenience
1930s 1950 1980 1995 2003 2007 2010
Intramuscular administration sc Injector
pens
sc, subcutaneous; FbM, filled by Mass; HP, highly-purified
Esteves, 18
Adapted from Lunenfeld. Hum Reprod Update 2004;10:453–67
19. Level
1a
Meta-
analyses of Number Number
Statistical Clinical
rec-hFSH vs of RCTs of
significance significance
HMG/HP- included couples
HMG/uFSH
Coomarasamy 7 2,159 LBR (RR = 1.18, 95% CI: 4% difference in
et al, 2008 1.02 to 1.38, P<0.03) in LBR in favor of
favor of HMG HMG (CI: 1%-?)
Insufficient evidence
Al Inany et al,
6 2,371 of a difference in odds None
2009
of pregnancy or live birth
Van Wely et al, 28 7,339 Insufficient evidence None
2011 of a difference in odds
of live birth
Subgroup analysis of r- For a LBR of 25%,
hFSH vs HMG in favor of use of rFSH rather
HMG (OR 0.84, 95% CI than hMG would
0.72 TO 0.99; N=3,197) result in a LBR
19%-25%
Coomarasamy et al, Hum Reprod. 2008;23:310-5; Al Inany et al, Gynecol Endocrinol. 2009;
Esteves, 19 25:372-8; Van Wely et al. Cochrane Database Syst Rev. 2011; 2:CD005354
20. Purity Mean specific LH Injected
(FSH activity activity protein
content) (IU/mg protein) per 75 IU
(IU/vial)
(mcg)
hMG < 5% ~100 75 ~750
hMG-HP < 70% 2,000–2,500 75 ~33
rec-hFSH
Follitropin – 7,000–10,000 0 8.1
beta
Follitropin > 99% 13,645 0 6.1
alfa
Esteves, 20 Bassett et al. Reprod Biomed Online 2005;10:169–177.
21. Conventional FbM: Novel
Bioassay analitycal method
High
Protein content by
Rat ovary mass
weight variability
gain Minimal batch-to-
batch variability
(1.6%)
Urinary gonadotropins
Follitropin beta Follitropin alfa
Bassett et al. Reprod Biomed Online 2005;10:169–177;
Esteves, 21 Driebergen et al. Curr Med Res Opin 2003;19:41–46.
22. Level
1b
Number of Retrieved Oocytes by the
Same Dose of rec-hFSH vs HP-HMG
↑ 1.5 oocytes (GnRH antagonist cycles)
Devroey et al., 2012
↑ 3.1 oocytes (GnRH antagonist cycles)
Bosch et al., 2008
↑ 1.8 oocytes
MERIT Study, 2006
↑ 2.8 oocytes (GnRH agonist cycles)
Hompes et al., 2008
Devroey P et al, Fertil Steril. 2012;97:561-71; Bosch E et al, Hum Reprod. 2008;23:2346-51; Nyboe
Andersen A, et al. Hum Reprod. 2006;21:3217–3227; Hompes PG et al, Fertil Steril. 2008;89:1685-93 ;
Esteves, 22
23. Level
2a
Total Dose per Live Birth (IU)* Reproductive Biology and Endocrinology 2009; 7:111.
10,000
52.2% 9,690 To achieve a live
7,000 21.6% 7,739 birth, 21-52%
more HP-hMG
6,324* and hMG was
3,000
required
compared with
0
rec-hFSH HP-hMG hMG rec-hFSH
*Mean total dose per cycle/Live birth rate (≤35 years)
Esteves, 23
24. Rec-hFSH vs Urinary products
Overall, recombinant and urinary gonadotropins
have comparable clinical efficacy, but this
does not mean drugs are the same.
Recombinant preparations have 3 major
differences compared to urinary products:
Higher purity and specific activity (SC delivery in
very small volumes))
Higher dose precision (FbM)
Higher potency (more oocytes retrieved)
Esteves, 24
25. Prevent
Can be
OHSS by
integrated in
GnRH-a
No flare spontaneous
GnRH antagonist and OI cycles Antagonist
effect with No hormonal
protocol administration
possible cyst withdrawal
formation Gonadotropin administration
Shorter
Can exclude duration of
early stimulation
pregnancy
Flare up Pituitary
effect suppression
Gonadotropin administration
Long GnRH
agonist Longer Agonist administration
protocol treatment
Pre-treatment cycle Treatment cycle
Esteves, 25
26. 1 2 3
pyro (Glu) – His – Trp – Ser – Tyr – Gly – Leu – Arg – Pro – Gly – NH2
Activation of the
Antagonistic Regulation of Regulation of receptor
GnRH receptor
effect receptor affinity biological activity
GnRH
Antagonists
Mode of
Action
Esteves, 26
27. Why introduction of antagonists in
clinical practice has been slow?
Experience with Agonists
Why change if it is working
Clinicians’ concerns:
Lower pregnancy rates
Not been able to program
aspirations on weekdays
LH surge (more monitoring)
Difficult to use
Esteves, 27
28. Level
1a
Probability of Live Birth
N studies 45 22
Included IUI Yes No
cycles
N patients 7511 3176
Primary outcome OPR or LBR LBR
Odds-ratio 0.86 0.86
(95% CI: 0.69-1.08) (95% CI: 0.72-1.02)
1. Al-Inany et al. Cochrane Database Syst Rev. 2011; 5:CD001750.
Esteves, 28 2. Kolibianakis et al. Hum Reprod Update. 2006;12:651.
29. Pre-treatment with OCP 4 RCT; 847 patients
Days of stimulation +1.41 (+1.13; +1.68)
Level
Gonadotropin consumption (UI) +542 (+127; +956)
1a
No. oocytes retrieved 1.63 (-0.34; 3.61)
Pregnancy rate (%) 0.74 (0.53; 1.03)
Griesinger et al. Fertil Steril 2008; 90:1055-63
Flexible* (N=68) Fixed on Day 6 (N=72) P>0.05
Level 29.7 29.2 24.7 23.3
12.0 10.3
1b 9.7 9.9
Days of Dose No. Oocytes Pregnancy (%)
stimulation gonadotropin *LH >10 IU/L, and/or mean follicle >12 mm, and/or
(x75UI) serum E2 >150 pg/mL; No LH surge reported
Esteves, 29
Kolibianakis EM, et al. Fertil Steril. 2011; 95:558-62
30. Level
1b
Day of hCG administration
RCT ≥3 follicles of One day
normogonadotropic ≥16mm later P
women <40 yrs. on value
antagonist COH N=52 N=54
No. Metaphase II
6.1 ± 4.9 9.2 ± 7.1 .009
oocytes
Fertilization rate (%) 66.7 ± 23.4 70.1 ± 20.9 .44
Pregnancy rate (%) 34.6% 40.7% .55
Kyrou D et al. Fertil Steril. 2011; 96(5):1112-5.
Esteves, 30 Kyrou D et al. Fertil Steril. 2011; 96(5):1112-5.
31. Recent Advances in Gonadotropins
Preparations
GnRH Agonist versus Antagonist
Clinical Outcomes Evidence
No difference in probability of live birth 1a
(overall and subgroups) compared to
agonists
No difference in flexible or fixed GnRH 1b
antagonist protocols
OCP programming not detrimental 1b
Delaying hCG by 1 day not detrimental 1b
Esteves, 31
32. Normal
• ~80% normogonadotropic women (WHO II)
undergoing Ovarian Stimulation1-3
• 15-20% of NG women have less sensitive
ovaries
• Older patients (≥35 years)4
Low
• Poor responders5
• Slow/Hypo-responders6
• Deeply suppressed endogenous LH
(endometriosis)7
1. Alviggi et al. Reprod Biomed Online 2006;12:221; 2. Tarlatzis et al. Hum Reprod
2006;21:90; 3. Esteves et al. Reprod Biol Endocrinol 2009;7:111; 4. Marrs et al. Reprod
Biomed Online 2004;8:175;5. Mochtar MH, Cochrane Database, 2007; 6. Alviggi, et al.
Esteves, 32 RBMOnline 2009; 7. De Placido et al. Clin Endocrinol (Oxf) 2004;60:637;
33. LH • Theca cells
Increase in LH
drive
LH • Granulosa
cells
Increase in FSH
drive FSH
Increasing the Number % Cycle Pregnancy
Level Stimulation Dose of oocytes cancellation rates
1b retrieved
FSH…
Manzi et al, 1994
Klinkert et al, 2004 …is not associated with better IVF
Berkkanoglu & Ozgur, 2010 outcome
Esteves, 33
34. Up to 45%
Infertility
Patients
• Older patients (≥35 years) aged 35 or
Less Sensitive Ovaries
• Poor responders above
• Slow/Hypo-responders
• Deeply suppressed endogenous LH (endometriosis)
Poor Responders* Hypo/Slow Responders
At least 2 of the following: Normal markers of ovarian reserve
Advanced maternal age (≥40 years) Hypo-responders:
Previous POR (≤3 oocytes with a d1-d7: normal initial follicullar recruitment
conventional stimulation protocol) using fixed starting dose of FSH; d7-
Abnormal ovarian reserve test (AFC<5; d10: plateau on follicullar growth
AMH <1.1) despite continuing same FSH dosage
Or: Slow responders:
2 episodes of POR after maximal High doses of FSH (>3,000UI) to promote
stimulation follicular growth;
May indicate genetic polymorphisms
of LH and/or FSH receptor
Marrs et al. Reprod Biomed Online 2004;8:175
De Placido et al. Clin Endocrinol (Oxf) 2004;60:637; Ferraretti et al. Fertil Steril. 2004; 82:1521-6;
Esteves, 34 Mochtar MH, Cochrane Database, 2007; Alviggi, et al. RBMOnline 2012
35. Level LH Supplementation in Poor
1a Responders…
Effect on
Regimen Outcome
Pregnancy
Mochtar et al, 2007
r-hFSH+rLH vs. OR 1.85
3 RCT (N=310) OPR
r-hFSH alone* (95% CI: 1.10; 3.11)
Poor responders
CPR RD: +6%,
Bosdou et al, 2012 r-hFSH+rLH vs. (95% CI: -0.3; +13.0)
7 RCT (N= 603) r-hFSH alone*
Poor responders LBR RD: +19%
(only 1 RCT) (95% CI: +1.0; +36.0%)
Hill et al, 2012
r-hFSH+rLH vs.
7 RCT (N=902) OR 1.37
r-hFSH alone CPR
Women advanced (95% CI: 1.03; 1.83)
age ≥35 yrs.
*long GnRH-a protocol; OR=odds-ratio; RD=risk difference
Mochtar MH et al. Cochrane Database Syst Rev. 2007;2:CD005070; Bosdou JK et al,
Esteves, 35 Hum Reprod Update 2012; 8(2):127-45. Hill MJ et al. Fertil Steril 2012; 97:1108-4.
36. Level LH Supplementation in
1b
Hypo/Slow Responders…
RCT 260 pts; “Steady” response on D8
(E2 <180 pg/mL; >6 follicles <10mm)
Mean No. oocytes retrieved IR (%) OPR (%)
40
32
22
18
14
10 9 11
6
FSH step-up (+150 UI) LH supplementation Normal Responders
(+150 UI)
Esteves, 36 De Placido et al. Hum Reprod. 2004; 20: 390-6.
37. Level To Whom to give LH
1b Supplementation in OI and IUI
LH levels 1.2 UI/L (WHO group I)
Higher follicular development pts. receiving LH (67% vs 20%;
p=0.02): Shoham, 2008.
Similar follicular development HMG vs FSH+rLH; higher
cumulative PR after 3 cycles in FSH+LH (56% vs 23%; p=0.01):
Carone, 2012.
WHO group II
Clomiphene-resistant: fewer intermediate-sized follicles and OHSS in
LH-supl. vs FSH group; similar ovulation rate (Plateau, 2006);
Previous over-response: higher monofollicular development in LH group
(32% vs 13%; p=0.04): Hughes, 2005;
IUI: higher monofollicular development in LH group without
intermediate-size (42% vs 11%; p=0.03); lower cycle cancellation due
to risk OHSS (-7% difference): Segnella 2011.
Esteves, 37
38. What is the optimal LH
supplementation protocol?
Existing studies give us some clues but the
optimal LH protocol has yet to be established
How much LH should be used?
Should the dose be fixed or flexible?
At what stage of the cycle should LH be
administered?
FSH
LH
2:1? 1:1? Fixed? Mimic of
natural LH levels?
Esteves, 38
39. Alfa Unit Beta unit Carboxyl terminal
(biological action segment
and receptor affinity) (determines half-life)
LH 92 AA; 121 AA Absent; half life of 20’
hCG Identical to LH 144 AA Present; half-life of 24h
Higher receptor affinity
Purity FSH LH activity
(LH content) activity (IU/vial) (IU/vial)
Rec-hLH >99% 0 75
Rec-hLH + rec-hFSH >99% 150 75
hMG-HP Unknown* 75 75*
*derives primarily from the hCG component, which preferentially is
concentrated during the purification process and sometimes was added
to achieve the desired amount of LH-like biological activity.
Esteves, 39 ASRM Practice Committee. Fertil Steril. 2008; 90:S13-20.
40. Level Differences in LH activity of rec-hLH
2a and HMG preparations
Matched case-control study;
N=4,719 pts.; long GnRH-a protocol
35
30 Duration of
P=0.02 31 Stimulation (days)
25
26 25 Mean No. oocytes
20 retrieved
15
IR (%)
10
5 CPR per transfer
(%)
0
2:1 r-hFSH+r- HMG rec-hFSH +
hLH HMG
Esteves, 40
Buhler KF, Fisher R. Gynecol Endocrinol 2011; 1-6.
41. Level
1a
Lower expression of LH/hCG receptor gene as well
as genes involved in in biosynthesis of cholesterol
and steroids in granulosa cells in pts. treated with
HMG preparations
May reflect down-regulation of LH receptors, as shown in animals:
Caused by a constant ligand exposure during the follicular
phase due to longer half life and higher binding affinity of
hCG to LHr
May explain the observed lower progesterone levels:
Caused by lower LH-induced cholesterol uptake, a decrease in
the novo cholesterol synthesis and a decrease in steroid
synthesis.
Trinchard-Lugan I et al. Reprod Biomed Online 2002; 4:106-115; Menon KM et al. Biol Reprod
Esteves, 41
2004; 70:861-866; Grondal ML et al. Fertil Steril 2009; 91: 1820-1830.
42. To whom to give rec-hLH?
Differences between rec-hLH and HMG preparations
15-20% women have less sensitive ovaries
and worse outcomes in IVF.
LH supplementation to OS is an evidence-
based strategy to maximize pregnancy results.
LH activity in HMG is hCG-dependent:
hCG is concentrated during purification or added to achieve
the desired amount of LH-like biological activity.
Lower expression of LH receptor gene in pts.
Treated with HMG (LHr down-regulation).
Preparations used are important for granulosa cell function
and may influence the developmental competence of the
Esteves, 42
oocyte and the function of corpus luteum.
43. What is in it for me?
1 Use of Biomarkers to Individualize Ovarian
Stimulation Protocols
Recent Advances in Gonadotropins Preparations
Rec-FSH vs urinary products
GnRH Agonist versus Antagonist
To whom to give rec-hLH? Differences between rec-
hLH and LH activity in HMG preparations?
Strategies to Improve Ovarian Stimulation
Best Protocols to Minimize Risks and Reduce Dropout
Rates in IVF
Esteves, 43
44. Strategies to Improve Ovarian
Stimulation
Up to 65% of couples dropout from IVF
without achieving pregnancy before they
complete 3 cycles
Reasons Pregnancy loss 94%
Psychological burden 49%-26% Unsuccessful cycle 87%
Prognosis 40%-23% Waiting after ET 81%
Waiting to find out how many 68%
Cost of treatment 23%-0% eggs fertilized
Relationship/divorce 15%-9% Result of pregnancy scan 47%
Physical burden 7-6%
Olivius K et al, Fertil Steril 2004;81:258; Land JA et al, Fertil Steril 1997; 68:278; Schroder AK, et al,
RBM Online 2004; 5:600; Osmanangaoglu K et al, Hum Reprod 2002; 17:2655; Rajkhowa M et al,
Hum Reprod 2006; 21:358; Brandes M et al, Hum Reprod 2009; 24:3127; Hammarberg K et al, Hum
Esteves, 44 Reprod 2001; 16:374.
45. Level
2a
Patient Preferences
68% Easy of use 58%
Reasons
Dosing mechanism 43%
25% Less chance of error 26%
7%
Folitropin alfa Follitropin beta Needle-free
prefilled cartridge and reconstitution, • Allowed injections at
ready-to-use reusable pen conventional home
pen syringe
• Improved pts.
satisfaction (QOL)
Weiss N. RBMonline 2007;15:31-7
Esteves, 45
46. • Same injection device
design for all
gonadotropins;
• Color-coded for
differentiation;
• Pre-filled, ready-to-
use family of pens for
fertility treatment.
Esteves, 46
48. Level AMH and AFC to Determine
2a
Who is Who Prior to OS
Response to Anti- Antral False
Ovarian Mullerian Follicle Positive
Stimulation Hormone Count Rate
(ng/mL)
Risk of Excessive
Response (≥15 ≥ 3.5 > 15
oocytes or OHSS)
Risk of Poor ~15%
Response < 1.1 <5
(≤ 4 oocytes)*
pmol/L X1000/140
*Bologna criteria: Ferraretti et al. Hum Reprod 2011; Broer et al. Hum Reprod Update 2011;
Esteves, 48 Nelson et al. Hum Reprod. 2009; Broer et al. Fertil Steril. 2009; Hendricks et al. Fertil Steril 2007.
49. Level Reduced Starting Doses of
2a
r-hFSH for Ovarian Stimulation in
High Responders
Clinical pregnancy rates/cycle
started
Individualized
60%
dosing in
50%
increments of 37.5 50.0%
IU of folitropin alfa 40%
possible by FbM 30% 35.3%
31.3% 31.1%
technology
20%
20.0%
Age (28-32) 10%
Oocytes retrieved 0%
75 IU 112.5 IU 150 IU 187.5 IU 225 IU
(8-12)
Esteves, 49 Olivennes F, et al. The CONSORT study. Reprod Biomed Online. 2009;18:95–204.
50. Level GnRH Antagonist Protocol in
1a
High Responders
9 RCT; 966 PCOS women Relative Risk
Duration of ovarian stimulation -0.74 (95% CI -1.12; -0.36)
Gonadotropin dose -0.28 (95% CI -0.43; -0.13)
Oocytes retrieved 0.01 (95% CI -0.24-0.26)
Risk of OHSS 20% vs 32%
Mild 1.23 (95% CI 0.67-2.26)
Moderate and Severe 0.59 (95% CI 0.45-0.76)
Clinical PR 1.01 (95% CI 0.88; 1.15)
Miscarriage rate 0.79 (95% CI 0.49; 1.28)
40% reduction in moderate/severe OHSS by using
antagonists rather than agonists
Esteves, 50 Pundir J et al. RBM Online 2012; 24:6-22.
51. Level
1b
Tailor OS in High Responders
by AMH (AFC)
Combination of Reduced rFSH Doses and
GnRH Antagonist
rec-hFSH 150UI AMH (ng/mL) >2.1
Agonist Antagonist
Days of Stimulation 13 (12-14) 9 (8-11)*
No. Oocytes retrieved (n) 14 (10-19) 10 (8.5-13.5)*
OHSS 20 (13.9%) 0 (0%)*
Cancellation 4 (2.7%) 1 (2.9%)
CPR per transfer 40.1% 63.6%*
*P ≤ 0.01
Adapted from Nelson SM et al . Anti-Müllerian hormone-based approach to controlled
Esteves, 51 ovarian stimulation for assisted conception. Hum Reprod. 2009; 24(4):867-75.
52. Level GnRH Agonist for LH
1a Triggering in High Responders
GnRH-a triggering (0.2-1.5 mg): antagonist protocol;
Reduced if not eliminated risk for OHSS;
In specific high risk patients for OHSS and egg donation
programs should become the choice.
11 RCT – 1,055 women
Moderate/
LBR OPR
severe OHSS
Fresh autologous OR 0.44 OR 0.45 OR 0.10,
cycles (8 RCT) (0.29 - 0.68) (0.31 - 0.65) (0.01 to 0.82)
Donor recipient OR 0.90 OR 0.91 OR 0.06
cycles (3 RCT) (0.57 - 1.42) (0.59 -1.40) (0.01 - 0.31)
Youssef et al. Cochrane Database Syst Rev. 2011
Esteves, 52
53. GnRH Agonist for LH
Triggering in High Responders
Challenge is to Rescue Luteal Phase Insufficiency.
Options are:
Vitrification and FET in subsequent natural cycle
Level
vs coasting and Fresh ET same cycle
2b CPR: 50% vs 29% (P<0.05)
Garcia-Velasco, Fertil Steril, 2012
Modified luteal support improved delivery rate:
Level hCG bolus OPU day (1,500 UI) or 3x 500 UI boluses;
recLH; intense progesterone + estradiol; combined.
1b Delivery rates: 18% risk difference favoring hCG (before) X
6% (after modified luteal support).
Humaidan et al. Hum Reprod Update 2011.
Esteves, 53
54. 20092009
Cycles with GnRH
Antagonists 54%
Rec-hFSH 45%
15%
Rec-hFSH
+ HMG 43%
1999
2009
HMG 12%
Data supplied by REDLARA and ICMART
Esteves, 54
56. Level GnRH Antagonists in Poor
1b Responders
14 RCT (1,127 patients)
Duration of Number Cycle Clinical
stimulation Oocytes cancellation Pregnancy
retrieved
-1.9 days -0.17 1.01 1.23
(-3.6; -0.12) (-0.69; 0.34) (0.71; 1.42) (0.92, 1.66)
Limited Clinical Benefit
Shortcomings:
- Definition of poor responders
- Different gonadotropins regimens for OS
Esteves, 56 Pu D et al. Hum Reprod. 2011; 26:2742.
57. Level
1a
Meta-analytic Effect on
Intervention Population
Studies Pregnancy
Kyrou et al,20091 Poor Higher LBR1,2,3
Growth Hormone Kolibianakis et al, 20092 responders Higher PR2
Duffy et al, 20103 Higher CPR3
Poor Higher LBR
Testosterone Bosdou et al , 2012
responders Higher CPR
Rec-hLH Mochtar et al, 20071 Poor Higher OPR1
supplementation Bosdou et al, 20122 responders1,2 Higher LBR2
to rec-hFSH Hill et al, 20123 Age ≥35 yrs3 Higher CPR3
Kolibianakis et al, Hum Reprod Update 2009,15:613-22; Kyrou et al, Fertil Steril̀ 2009;91: 749–66; Duffy et al,
Cochrane Database Syst Rev 2010;1:CD000099; Mochtar MH et al. Cochrane Database Syst Rev.
2007,2:CD005070; Bosdou JK et al, Hum Reprod Update 2012;8:127-45; Hill MJ et al. Fertil Steril
Esteves, 57 2012;97:1108-4.
58. Strategies to Improve Success by
Tailoring Ovarian Stimulation
Best Strategies to Maintain
Sustainable Pregnancy Results Evidence
and Minimize Complications in
“High” Responders
Low Starting Doses of r-hFSH, preferably 2a
filled by mass preparations
GnRH Antagonists 1a
Biomarkers to tailor OS 1b
GnRH Agonist for LH Triggering1 1a
1Associated with lower pregnancy rates
Esteves, 58
59. Best Strategies to Maximize
Pregnancy Results Evidence
and Minimize Complications in
“Poor” Responders
GnRH Antagonists (lower OS duration) 1a
Adjuvant Therapy 1a
Growth hormone 1a
Testosterone 1a
LH supplementation
Poor responders 1a
Advanced age (≥35) 1a
Slow/Hypo responders 1b
Esteves, 59