This lecture discusses the role of LH in reproductive cycles. It notes that both FSH and LH are essential for normal estrogen biosynthesis and optimal follicular development occurs within an 'LH window' above a certain threshold but below a ceiling. The lecture also reviews evidence that 75IU of recombinant LH is sufficient to promote optimal follicular and endometrial growth in most hypogonadotropic hypogonadism patients. The central paradigm is to maximize beneficial effects of treatment while minimizing complications and risks.
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.
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.
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.
Optimal endometrial preparation for frozen embryo transfer cyclesnermine amin
This document discusses optimal endometrial preparation for frozen embryo transfer (FET) cycles. It describes different preparation protocols including natural, modified natural, and programmed artificial cycles. Programmed cycles use estrogen and progesterone supplementation to prepare the endometrium. The document emphasizes identifying the receptive implantation window and the importance of progesterone support. Personalizing FET timing based on endometrial development and reducing uterine contractions with progesterone can improve pregnancy rates. With advances in cryopreservation, FET cycles now often match or exceed the success of fresh cycles.
This document discusses poor ovarian responders in assisted reproductive technology treatment. It defines poor ovarian response based on the Bologna criteria of fewer than 3 oocytes retrieved with conventional stimulation. Poor responders make up 9-24% of IVF patients. The document outlines limitations of the Bologna criteria and introduces the POSEIDON classification system, which categorizes patients based on age, ovarian reserve markers, and ovarian response. It discusses markers for predicting poor response and reviews strategies for managing poor responders, including use of recombinant FSH, increasing FSH dosage, adding recombinant LH, and DHEA supplementation.
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
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.
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.
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.
Optimal endometrial preparation for frozen embryo transfer cyclesnermine amin
This document discusses optimal endometrial preparation for frozen embryo transfer (FET) cycles. It describes different preparation protocols including natural, modified natural, and programmed artificial cycles. Programmed cycles use estrogen and progesterone supplementation to prepare the endometrium. The document emphasizes identifying the receptive implantation window and the importance of progesterone support. Personalizing FET timing based on endometrial development and reducing uterine contractions with progesterone can improve pregnancy rates. With advances in cryopreservation, FET cycles now often match or exceed the success of fresh cycles.
This document discusses poor ovarian responders in assisted reproductive technology treatment. It defines poor ovarian response based on the Bologna criteria of fewer than 3 oocytes retrieved with conventional stimulation. Poor responders make up 9-24% of IVF patients. The document outlines limitations of the Bologna criteria and introduces the POSEIDON classification system, which categorizes patients based on age, ovarian reserve markers, and ovarian response. It discusses markers for predicting poor response and reviews strategies for managing poor responders, including use of recombinant FSH, increasing FSH dosage, adding recombinant LH, and DHEA supplementation.
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
Treatment of poor responders: Review of Systematic reviews 2016 Aboubakr Elnashar
The document summarizes evidence from systematic reviews on treatments for poor responders undergoing IVF. It finds that flare up GnRH agonist protocols, estrogen primed antagonist protocols, DHEA supplementation, and transdermal testosterone are associated with increased clinical pregnancy rates compared to other interventions. The document also reviews interventions such as growth hormone, luteal phase estrogen, corticosteroids, and embryo transfer on day 2 versus day 3. It aims to determine the best evidence on treatments for poor responders based on systematic reviews published between 2003 and 2016.
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.
PROTOCOLSIntra Uterine Insemination (sharing personal experience) Lifecare Centre
This document provides information on intrauterine insemination (IUI), including prerequisites, indications, steps, and factors affecting success rates. It summarizes that IUI is a relatively simple and inexpensive fertility treatment that involves placing sperm directly into the uterus. Success rates are affected by factors like total motile sperm count, with counts over 5 million critical. Density gradient preparation is superior to swim-up for abnormal semen. DNA fragmentation levels also impact rates. Guidelines on when to consider IVF instead of further IUI cycles include age over 37, more than 4 failed cycles, severe male factors, and certain ovarian response patterns.
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.
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.
This document summarizes current evidence on medical add-ons used in in vitro fertilization (IVF). It discusses adjuvants used to improve ovarian response and implantation success, including DHEA, growth hormone, antioxidants, artificial oocyte activation, estrogen, and metformin. For each adjuvant, the proposed mechanisms of action and available evidence from studies are summarized. In general, the evidence for most add-ons is limited and inconclusive due to small study sizes and heterogeneity. High-quality randomized controlled trials are still needed to establish efficacy and safety.
There are three main methods for endometrial preparation in frozen embryo transfer cycles:
1) Natural cycles which rely on endogenous hormones but have limitations like irregular cycles.
2) Hormonally manipulated cycles using GnRH agonists and exogenous estrogen and progesterone to control timing, but GnRH agonists are not always needed.
3) Non-GnRH agonist manipulated cycles using exogenous estrogen and progesterone alone, which is a simple and effective alternative to GnRH agonist protocols.
The document discusses various hormone replacement protocols and finds no significant differences in outcomes between natural, GnRH agonist, and non-GnRH agonist methods of endometrial preparation.
This document discusses different methods for endometrial preparation in frozen embryo transfer cycles. It summarizes that:
1) Natural cycles can be used for younger patients but have limitations like irregular cycles and difficulty timing ovulation.
2) Hormonally controlled cycles using estrogen and progesterone with or without GnRH agonists are effective options. Exogenous hormone administration without GnRH agonists is now commonly used as it is simple and effective.
3) Factors like embryo quality and endometrial thickness predict success, but preparation method, hormone type/administration, and cryostorage length do not affect outcomes. The best predictors are good quality embryos and a tri-laminar endometrial pattern.
Since the first formal description of LPD in 1949 as a possible cause of infertility and recurrent miscarriage by Jones. Innumerable investigations have been undertaken in an effort to verify its existence or to characterize its pathophysiology, diagnosis, and treatment. The consensus of the literature is that LPD does exist and that its cause is multifactorial like abnormal folliculogenesis, inadequate LH surge,inadequate secretion of progesterone by the corpus luteum, aberrant end-organ response by the endometrium.
Ovarian Stimulation in IUI- Overview Sr. Jyoti BhaskarLifecare Centre
The document discusses ovarian stimulation protocols for intrauterine insemination (IUI) in subfertile women. It provides information on the rationale for controlled ovarian hyperstimulation (COH) in IUI, including increasing the number of eggs and overcoming subtle defects. The aim of COH is to recruit multiple follicles, control ovulation timing, prevent premature LH surges, time insemination, and increase pregnancy rates. Optimal stimulation results in 2-3 follicles ≥18-19mm in size and a thick, trilaminar endometrium. Gonadotropins are more effective than anti-estrogens like clomiphene citrate for IUI, and low
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.
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 ovarian stimulation. It begins by describing the different types of anovulation and ovarian stimulation protocols. It then discusses the different types of gonadotropin (Gnt) preparations including urinary and recombinant gonadotropins. Patient selection criteria and indications for ovarian stimulation are outlined. A low-dose step-up protocol is recommended to reduce risks of ovarian hyperstimulation syndrome and multiple pregnancies. Monitoring involves ultrasounds and bloodwork. Ovulation rates are over 90% while pregnancy rates range from 5-90% depending on factors. Complications include ovarian hyperstimulation syndrome and multiple pregnancies.
This document provides guidelines for the management of thin endometrium based on evidence from studies. It discusses measurement of endometrial thickness, incidence of thin endometrium, potential causes, and impact on treatment outcomes. For ovarian stimulation cycles, fresh embryo transfers, and frozen embryo transfers, it examines the evidence and provides recommendations regarding counseling patients, elective cryopreservation, and use of adjuvants to improve outcomes for those with thin endometrium. However, it finds that currently there is limited evidence to support specific protocols or treatments for improving pregnancy rates.
This document discusses new developments in controlled ovarian stimulation (COS) protocols. It outlines several new forms of fertility drugs including long acting FSH, FSH biosimilars, and subcutaneous progestagens. It also describes new COS protocols such as those using fewer injections, flexibility in start dates, dual stimulation, and individualizing FSH dosing to prevent ovarian hyperstimulation syndrome. The document concludes that while further research is still needed, these new drugs and protocols provide valuable options for increasing flexibility and optimizing outcomes in ART treatment.
Evidence for a significant effect in favor of progesterone for luteal phase support. Best result with synthe7c progesterone.
• Evidence that the addi7on of othe substances such as estrogen or hCG doe not improve outcomes.
• Evidence for equivalence of IM and vaginal routes of administra7on. Vaginal route is best tolerated by pa7ents.
• hCG, or hCG plus progesterone, was associated with a higher risk of OHSS. The use of hCG should therefore be avoided.
• Evidence showing a benefit from the addi7on of GnRH agonist to progesterone in luteal phase support
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.
Vasundhara Hospital Jaipur is a premier specialty hospital for infertile couples, complete women care, high risk pregnancy management, located in heart of Jaipur.
Click to more info :- https://www.vasundharafertility.com/jaipur
Recombinant hCG: state-of -art formulation for a patient-centered management ...Sandro Esteves
This document discusses the use of recombinant human chorionic gonadotropin (rec-hCG) compared to urinary hCG (u-hCG) for oocyte maturation triggering in in vitro fertilization (IVF). Recombinant hCG is produced from cultured cells and has higher purity than u-hCG extracted from urine. It has consistent characteristics that allow precise dosing and a better safety profile. Studies show rec-hCG results in higher fertilization rates and pregnancy rates compared to u-hCG when used for oocyte triggering in IVF. Recombinant hCG also allows for subcutaneous administration using pre-filled syringes or pens, providing more convenient treatment compared to u
Legal Heights Consultants provides recruitment services including recruitment process outsourcing, executive search, permanent staffing, and contract staffing. Their vision is to create a world-class platform that transforms lives, and their mission is to continuously delight customers through superior value and enhanced offerings. They serve industries such as temporary staffing, telecom, facilities management, retail, FMCG, banking, and financial services. Their recruitment process involves understanding client requirements, identifying suitable candidates, scheduling interviews, and negotiating terms until candidates are hired. Their registered office is located in Bangalore, India.
Treatment of poor responders: Review of Systematic reviews 2016 Aboubakr Elnashar
The document summarizes evidence from systematic reviews on treatments for poor responders undergoing IVF. It finds that flare up GnRH agonist protocols, estrogen primed antagonist protocols, DHEA supplementation, and transdermal testosterone are associated with increased clinical pregnancy rates compared to other interventions. The document also reviews interventions such as growth hormone, luteal phase estrogen, corticosteroids, and embryo transfer on day 2 versus day 3. It aims to determine the best evidence on treatments for poor responders based on systematic reviews published between 2003 and 2016.
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.
PROTOCOLSIntra Uterine Insemination (sharing personal experience) Lifecare Centre
This document provides information on intrauterine insemination (IUI), including prerequisites, indications, steps, and factors affecting success rates. It summarizes that IUI is a relatively simple and inexpensive fertility treatment that involves placing sperm directly into the uterus. Success rates are affected by factors like total motile sperm count, with counts over 5 million critical. Density gradient preparation is superior to swim-up for abnormal semen. DNA fragmentation levels also impact rates. Guidelines on when to consider IVF instead of further IUI cycles include age over 37, more than 4 failed cycles, severe male factors, and certain ovarian response patterns.
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.
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.
This document summarizes current evidence on medical add-ons used in in vitro fertilization (IVF). It discusses adjuvants used to improve ovarian response and implantation success, including DHEA, growth hormone, antioxidants, artificial oocyte activation, estrogen, and metformin. For each adjuvant, the proposed mechanisms of action and available evidence from studies are summarized. In general, the evidence for most add-ons is limited and inconclusive due to small study sizes and heterogeneity. High-quality randomized controlled trials are still needed to establish efficacy and safety.
There are three main methods for endometrial preparation in frozen embryo transfer cycles:
1) Natural cycles which rely on endogenous hormones but have limitations like irregular cycles.
2) Hormonally manipulated cycles using GnRH agonists and exogenous estrogen and progesterone to control timing, but GnRH agonists are not always needed.
3) Non-GnRH agonist manipulated cycles using exogenous estrogen and progesterone alone, which is a simple and effective alternative to GnRH agonist protocols.
The document discusses various hormone replacement protocols and finds no significant differences in outcomes between natural, GnRH agonist, and non-GnRH agonist methods of endometrial preparation.
This document discusses different methods for endometrial preparation in frozen embryo transfer cycles. It summarizes that:
1) Natural cycles can be used for younger patients but have limitations like irregular cycles and difficulty timing ovulation.
2) Hormonally controlled cycles using estrogen and progesterone with or without GnRH agonists are effective options. Exogenous hormone administration without GnRH agonists is now commonly used as it is simple and effective.
3) Factors like embryo quality and endometrial thickness predict success, but preparation method, hormone type/administration, and cryostorage length do not affect outcomes. The best predictors are good quality embryos and a tri-laminar endometrial pattern.
Since the first formal description of LPD in 1949 as a possible cause of infertility and recurrent miscarriage by Jones. Innumerable investigations have been undertaken in an effort to verify its existence or to characterize its pathophysiology, diagnosis, and treatment. The consensus of the literature is that LPD does exist and that its cause is multifactorial like abnormal folliculogenesis, inadequate LH surge,inadequate secretion of progesterone by the corpus luteum, aberrant end-organ response by the endometrium.
Ovarian Stimulation in IUI- Overview Sr. Jyoti BhaskarLifecare Centre
The document discusses ovarian stimulation protocols for intrauterine insemination (IUI) in subfertile women. It provides information on the rationale for controlled ovarian hyperstimulation (COH) in IUI, including increasing the number of eggs and overcoming subtle defects. The aim of COH is to recruit multiple follicles, control ovulation timing, prevent premature LH surges, time insemination, and increase pregnancy rates. Optimal stimulation results in 2-3 follicles ≥18-19mm in size and a thick, trilaminar endometrium. Gonadotropins are more effective than anti-estrogens like clomiphene citrate for IUI, and low
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.
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 ovarian stimulation. It begins by describing the different types of anovulation and ovarian stimulation protocols. It then discusses the different types of gonadotropin (Gnt) preparations including urinary and recombinant gonadotropins. Patient selection criteria and indications for ovarian stimulation are outlined. A low-dose step-up protocol is recommended to reduce risks of ovarian hyperstimulation syndrome and multiple pregnancies. Monitoring involves ultrasounds and bloodwork. Ovulation rates are over 90% while pregnancy rates range from 5-90% depending on factors. Complications include ovarian hyperstimulation syndrome and multiple pregnancies.
This document provides guidelines for the management of thin endometrium based on evidence from studies. It discusses measurement of endometrial thickness, incidence of thin endometrium, potential causes, and impact on treatment outcomes. For ovarian stimulation cycles, fresh embryo transfers, and frozen embryo transfers, it examines the evidence and provides recommendations regarding counseling patients, elective cryopreservation, and use of adjuvants to improve outcomes for those with thin endometrium. However, it finds that currently there is limited evidence to support specific protocols or treatments for improving pregnancy rates.
This document discusses new developments in controlled ovarian stimulation (COS) protocols. It outlines several new forms of fertility drugs including long acting FSH, FSH biosimilars, and subcutaneous progestagens. It also describes new COS protocols such as those using fewer injections, flexibility in start dates, dual stimulation, and individualizing FSH dosing to prevent ovarian hyperstimulation syndrome. The document concludes that while further research is still needed, these new drugs and protocols provide valuable options for increasing flexibility and optimizing outcomes in ART treatment.
Evidence for a significant effect in favor of progesterone for luteal phase support. Best result with synthe7c progesterone.
• Evidence that the addi7on of othe substances such as estrogen or hCG doe not improve outcomes.
• Evidence for equivalence of IM and vaginal routes of administra7on. Vaginal route is best tolerated by pa7ents.
• hCG, or hCG plus progesterone, was associated with a higher risk of OHSS. The use of hCG should therefore be avoided.
• Evidence showing a benefit from the addi7on of GnRH agonist to progesterone in luteal phase support
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.
Vasundhara Hospital Jaipur is a premier specialty hospital for infertile couples, complete women care, high risk pregnancy management, located in heart of Jaipur.
Click to more info :- https://www.vasundharafertility.com/jaipur
Recombinant hCG: state-of -art formulation for a patient-centered management ...Sandro Esteves
This document discusses the use of recombinant human chorionic gonadotropin (rec-hCG) compared to urinary hCG (u-hCG) for oocyte maturation triggering in in vitro fertilization (IVF). Recombinant hCG is produced from cultured cells and has higher purity than u-hCG extracted from urine. It has consistent characteristics that allow precise dosing and a better safety profile. Studies show rec-hCG results in higher fertilization rates and pregnancy rates compared to u-hCG when used for oocyte triggering in IVF. Recombinant hCG also allows for subcutaneous administration using pre-filled syringes or pens, providing more convenient treatment compared to u
Legal Heights Consultants provides recruitment services including recruitment process outsourcing, executive search, permanent staffing, and contract staffing. Their vision is to create a world-class platform that transforms lives, and their mission is to continuously delight customers through superior value and enhanced offerings. They serve industries such as temporary staffing, telecom, facilities management, retail, FMCG, banking, and financial services. Their recruitment process involves understanding client requirements, identifying suitable candidates, scheduling interviews, and negotiating terms until candidates are hired. Their registered office is located in Bangalore, India.
Role of LH supplementation in reproductive medicine - Aspire 2013Sankalp Singh
To add or not to add LH is a highly contentious issue.Here,i would be discussing role of LH supplementation in IVF cycle as per present day evidence.
Also,will be scrutinising the available studies for their reliability or lack of it.
This document discusses polycystic ovary syndrome (PCOS) and its implications. It begins with the diagnostic criteria for PCOS including hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. It then covers the diagnostic workup involving physical exams, laboratory tests, ultrasound, and optional tests. The document discusses the implications of PCOS for health including metabolic syndrome and future cardiovascular risks. It covers the implications for infertility such as treatments including lifestyle changes, clomiphene citrate, gonadotropins, laparoscopic ovarian drilling, metformin, and assisted reproduction. The implications for pregnancy with PCOS including gestational diabetes, pregnancy induced hypertension, preterm birth, birth weight,
This document discusses the use of recombinant luteinizing hormone (rLH) in assisted reproduction. It begins by asking if an appropriate patient population has been defined that could benefit from rLH supplementation. It then discusses LH and FSH action on follicles, the LH therapeutic window concept, and how central nervous system influence can cause hypothalamic-pituitary-hypogonadism. The document presents studies showing improved follicular development and outcomes like pregnancy rates with the addition of rLH for poor responders and women over 35 undergoing fertility treatments. It also discusses dose-finding studies that identified a safe and effective dose of 75IU/day rLH. In conclusion, the risks of rLH supplementation are addressed as
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
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 appears to be a presentation on LH and its role in human reproduction given by Dr. Sandro Esteves. The presentation covers several key points:
1) LH plays an important role in reproductive cycles through its effects on steroidogenesis, follicular growth, and oocyte maturation.
2) Certain patient groups may benefit from LH supplementation during ovarian stimulation, including poor responders, older women (>35), and those using a GnRH antagonist protocol.
3) The rationale for LH supplementation in older women and poor responders is that it helps restore hormonal balance and the follicular environment by increasing androgen and estrogen production through its effects on the ovaries and granulosa cells.
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.
The document discusses prolactin, a hormone produced by the pituitary gland. It notes that prolactin is a single chain polypeptide hormone composed of 199 amino acids. Prolactin has over 300 effects in the body and is primarily involved in modulating processes like lactation. The document outlines the factors that stimulate and inhibit prolactin production, as well as the effects of hyperprolactinemia, including decreased libido and bone mineral density.
This document discusses various ovulation induction protocols including:
- Clomiphene citrate is commonly used as a first line treatment but some women are clomiphene resistant.
- Gonadotropins like hMG can cause multifollicular development and increase risks of complications like OHSS.
- A novel protocol uses a combination of hMG for several days followed by clomiphene to promote monofollicular development while reducing risks of complications. Initial studies found this protocol increased follicle recruitment over hMG alone without increasing LH levels or risks.
Progesterone elevation on the day of HCG administration in ivfAboubakr Elnashar
Progesterone elevation on the day of HCG administration in IVF can negatively impact pregnancy rates. The incidence of progesterone elevation varies widely due to differences in definitions, patient populations, and treatment protocols. Several hypotheses for the pathogenesis of progesterone elevation exist, including incomplete pituitary suppression leading to elevated follicular LH levels or increased LH receptor sensitivity in granulosa cells. Prevention strategies include using a flexible antagonist protocol, low-dose HCG alone in late ovarian stimulation, mifepristone administration, or aspiration of a single leading follicle.
Principles and Practices of LH Administration in Controlled Ovarian StimulationSandro Esteves
The document discusses principles of LH supplementation during controlled ovarian stimulation (COS) cycles. It begins by outlining how the author practices LH supplementation in different patient populations during COS using either recombinant human LH (rec-LH) or human menopausal gonadotropin (hMG), which contains LH activity from hCG. It then reviews the principles of LH supplementation, molecular differences between LH and hCG, and clinical outcomes when using preparations containing LH activity.
This document summarizes the principles and practices of LH administration in assisted reproductive technology (ART). It discusses the role of LH in reproductive cycles, patient subgroups that may benefit from LH supplementation, and differences in LH supplementation using various gonadotropin preparations. Specifically, it finds that LH supplementation can benefit older patients, poor responders, and hypo-responders by restoring androgen production and improving follicular development, oocyte quality, and pregnancy rates.
This meta-analysis compared commercially available HP-FSH to recombinant FSH (rFSH) in women undergoing IVF/ICSI. It found that HP-FSH was not inferior to rFSH for clinical pregnancy and ongoing pregnancy/live birth rates. It also found that HP-FSH required fewer treatment days and total FSH dose than rFSH to achieve similar results. However, some heterogeneity was present between the included trials. The author calls for more randomized controlled trials and cost-effectiveness analyses to further evaluate HP-FSH versus rFSH.
The Need of LH in ART and Differences Between Sources of LH ActivitySandro Esteves
This document discusses the role of luteinizing hormone (LH) in reproductive cycles and ovarian stimulation. It summarizes that LH is essential for normal ovarian steroidogenesis and follicular development. Certain patient groups, such as older women, poor responders, and those with less sensitive ovaries may benefit from LH supplementation during controlled ovarian stimulation cycles to help maximize pregnancy rates. The document reviews several randomized controlled trials comparing recombinant follicle-stimulating hormone alone versus in combination with recombinant LH, finding improved outcomes with LH addition in some patient populations.
Lh in assisted reproduction by DR G A RAMARAJUG A RAMA Raju
Luteinizing hormone (LH) in synergy with follicle stimulating hormone (FSH) stimulates normal follicular growth and ovulation. FSH is frequently used in assisted reproductive technology (ART). Recent studies have facilitated better understanding on the complementary role of the LH to FSH in regulation of the follicle; however, role of LH in stimulation of follicle, optimal dosage of LH in stimulation and its importance in advanced aged patients has been a topic of discussion among medical fraternity. Though the administration of exogenous LH with FSH is obligatory for controlled ovarian stimulation in patients with hypogonadotropic hypogonadism, there is still a paucity of information of its usage in other patient population.A Brief introduction of Lh polymorphism in ovarian stimulation
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.
This document discusses effective protocols for superovulation when undergoing IVF treatment. It compares different ovarian stimulation protocols including long and short protocols using gonadotropin-releasing hormone (GnRH) agonists or antagonists. It also examines the use of human menopausal gonadotropin (hMG) versus recombinant follicle-stimulating hormone (r-FSH), as well as adding luteinizing hormone (LH) to stimulation. Key factors discussed include number of eggs retrieved, egg and embryo quality, risk of ovarian hyperstimulation syndrome, and pregnancy rates. The document provides guidance on optimizing protocols based on patient characteristics and treatment goals.
Male infertility current concepts for reproductive specialistsSandro Esteves
The document summarizes a presentation on novel concepts in male infertility. It discusses updated WHO reference values for semen analysis, the evidence-based use of antioxidants to treat male infertility, sperm DNA integrity testing and Y chromosome microdeletion screening, and the benefits of surgically treating varicocele before assisted reproduction techniques. Clinical trials show varicocele repair can improve sperm parameters, live birth rates with ICSI, and the chance of successful sperm retrieval in azoospermia.
New product dedisions provide a dear path to the business. New product development
astep by step process. A Complete idea is required behind new product.
1 1deal Generation: The development of a product starts with the concept and idea.
The remaining process is depending on that idea.
2 Screening of Idea: This step is cruial to ensure that unsuitable ideas, for whatever
reason, are rejected as soon as possible. Ideas need to be considered objectively,
ideally by a group or committee.
3. Concept Development and Testing: After having an idea, next is the sreening
stage. The idea should now convert into concept. It has depth information which can
be visualizing by the consumer.
4. Anaysis of business: After finalization of concept, a business case needs to be kept
algTStogether to consider whether the new service /product will be gainful.
2665.Product Development If the nev product is approved, it will be approved to the
2marketing and technical development step.
6. Test Marketing: Market testing (test marketing or) is different to consumer testing.
in that it introduces the product that follows proposed plan of marketing.
od7. Commercialization: When the concept has been tested and developed, final
0decisions are required to move the product to its introduction into the market.
8. Launch: A detailed plan of launch is required for this step. This is the important
stage for success of a product
New Drug Development
So In present business atmosphere, it is more important to take smart decisions for
business. Innovative approaches and new products can put an organization on proper
pathway and to make a big success if appropriately analyzed and executed. Make it simpler
(Fig.2.1).0
Following parameters should keep in mind for a better decision:
Analyzing existing service and product portfolio frequently.
Knowing the position of functions of business, projects of departments and
initiatives.
Understanding the distribution of funds and assessing efficiency.
Having understanding of market for new opportunities and possible competition.
2.B PRODUCT BRANDING, PACKAGING AND LABELLING DECİSIONs
2.8.1 Branding
Branding has its existence from ancient era. According to Nilson (2000), the first example
of branding is found in the oil lamps' manufacture on the Greek islands thousands of years
back. Brand elements are name, sign, term, symbol, design or distinguishing characteristics.
Brand is not only a graphical design or a logo; it is the unique identity of the product.
By American Marketing Association, Brand can be defined as name, term, sign, symbol
or design, or a combination of them intended to identijy the goods and services of one seller or
group of sellers and to diferentiate them from those of other sellersa54
Branding is a process, where a company generates loyalty among consumers in the
market. Brands are designed with a motive to communicate customers the reason for the
existence of their product. Brand should have a strong connection with customers;
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.
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.
Effect of Gonadotrophin (Pergonal®) on Haematological and Serum Biochemical P...Agriculture Journal IJOEAR
Abstract— Twelve Ouda rams aged 2 – 2.6 years and weighed between 40.21 – 40.32kg were randomly distributed into 3 groups of 4 animals with one ram per replicate in a completely randomized design and used to determine the effect of Pergonal® on haematology and serum biochemistry. These groups were assigned to 3 levels of Pergonal® injection as treatments. The injections were 0.00i.u, 49.50i.u, and 99.00i.u Pergonal® represented as T1 (control), T2, and T3, respectively. All the treatments were administered by intramuscular injections. The injections were divided into three doses each and administered intramuscularly in the thigh for three consecutive days. The results of the study showed that apart from Alanine transaminase and eosinophils, the haematological and serum biochemical parameters and immune status of ouda rams may be affected when 49.50i.u or more of Pergonal are used for induction of spermatogenesis. These parameters should be constantly monitored during pergonal administration in ouda rams.
The document discusses systems and assays that can be implemented by academic groups for central nervous system (CNS) drug discovery. It focuses on absorption, distribution, metabolism, and excretion (ADME) assays including solubility tests, pharmacokinetic studies, and metabolism experiments. It also covers toxicology assays such as in vitro safety tests and rodent tolerability studies. The level of characterization required depends on whether the compound is being developed as a research probe or as a potential investigational new drug (IND) candidate.
This document describes an experiment investigating the fibrillation kinetics of bovine and human insulin fragments and a tailored peptide. Key findings include:
- Bovine insulin fragments aggregated faster than human fragments under Thioflavin T fluorescence spectroscopy, indicating higher fibrillation propensity.
- Higher temperature (60°C) and lower pH (2.5) increased fibril formation compared to lower temperature (40°C) and higher pH (7.0).
- The tailored diblock peptide showed no fibril formation over 4 weeks under the experimental conditions.
The document outlines the professional background and accomplishments of Prof. Jaideep Malhotra, including his roles as Managing Director of Rainbow Hospitals, professorships, awards received, and contributions to the fields of IVF and reproductive medicine in India and Nepal. It also lists him as an editor for several medical journals and books. The second page provides an outline for his upcoming presentation on the ten secrets of ovarian stimulation.
Liposomes are spherical vesicles composed of phospholipid bilayers that can encapsulate hydrophilic or hydrophobic drugs. There are several types of liposomes including conventional, stealth, targeted, and cationic liposomes. Liposomes can be prepared using techniques like extrusion, sonication, and dehydration-rehydration. Differential scanning calorimetry is used to study the phase transition of lipids in liposomes. Drugs are encapsulated within the aqueous core or phospholipid bilayer of liposomes. In vivo, liposomes are targeted by plasma proteins and cleared by the liver and spleen, but PEGylation creates "stealth liposomes" that evade this clearance. Several liposomal drug formulations have been commercial
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.
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
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
Nutritional deficiency Disorder are problems in india.
It is very important to learn about Indian child's nutritional parameters as well the Disease related to alteration in their Nutrition.
Are you looking for a long-lasting solution to your missing tooth?
Dental implants are the most common type of method for replacing the missing tooth. Unlike dentures or bridges, implants are surgically placed in the jawbone. In layman’s terms, a dental implant is similar to the natural root of the tooth. It offers a stable foundation for the artificial tooth giving it the look, feel, and function similar to the natural tooth.
Giloy in Ayurveda - Classical Categorization and SynonymsPlanet Ayurveda
Giloy, also known as Guduchi or Amrita in classical Ayurvedic texts, is a revered herb renowned for its myriad health benefits. It is categorized as a Rasayana, meaning it has rejuvenating properties that enhance vitality and longevity. Giloy is celebrated for its ability to boost the immune system, detoxify the body, and promote overall wellness. Its anti-inflammatory, antipyretic, and antioxidant properties make it a staple in managing conditions like fever, diabetes, and stress. The versatility and efficacy of Giloy in supporting health naturally highlight its importance in Ayurveda. At Planet Ayurveda, we provide a comprehensive range of health services and 100% herbal supplements that harness the power of natural ingredients like Giloy. Our products are globally available and affordable, ensuring that everyone can benefit from the ancient wisdom of Ayurveda. If you or your loved ones are dealing with health issues, contact Planet Ayurveda at 01725214040 to book an online video consultation with our professional doctors. Let us help you achieve optimal health and wellness naturally.
The biomechanics of running involves the study of the mechanical principles underlying running movements. It includes the analysis of the running gait cycle, which consists of the stance phase (foot contact to push-off) and the swing phase (foot lift-off to next contact). Key aspects include kinematics (joint angles and movements, stride length and frequency) and kinetics (forces involved in running, including ground reaction and muscle forces). Understanding these factors helps in improving running performance, optimizing technique, and preventing injuries.
“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...Université de Montréal
“Psychiatry and the Humanities”: An Innovative Course at the University of Montreal Expanding the medical model to embrace the humanities. Link: https://www.psychiatrictimes.com/view/-psychiatry-and-the-humanities-an-innovative-course-at-the-university-of-montreal
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Osvaldo Bernardo Muchanga-GASTROINTESTINAL INFECTIONS AND GASTRITIS-2024.pdfOsvaldo Bernardo Muchanga
GASTROINTESTINAL INFECTIONS AND GASTRITIS
Osvaldo Bernardo Muchanga
Gastrointestinal Infections
GASTROINTESTINAL INFECTIONS result from the ingestion of pathogens that cause infections at the level of this tract, generally being transmitted by food, water and hands contaminated by microorganisms such as E. coli, Salmonella, Shigella, Vibrio cholerae, Campylobacter, Staphylococcus, Rotavirus among others that are generally contained in feces, thus configuring a FECAL-ORAL type of transmission.
Among the factors that lead to the occurrence of gastrointestinal infections are the hygienic and sanitary deficiencies that characterize our markets and other places where raw or cooked food is sold, poor environmental sanitation in communities, deficiencies in water treatment (or in the process of its plumbing), risky hygienic-sanitary habits (not washing hands after major and/or minor needs), among others.
These are generally consequences (signs and symptoms) resulting from gastrointestinal infections: diarrhea, vomiting, fever and malaise, among others.
The treatment consists of replacing lost liquids and electrolytes (drinking drinking water and other recommended liquids, including consumption of juicy fruits such as papayas, apples, pears, among others that contain water in their composition).
To prevent this, it is necessary to promote health education, improve the hygienic-sanitary conditions of markets and communities in general as a way of promoting, preserving and prolonging PUBLIC HEALTH.
Gastritis and Gastric Health
Gastric Health is one of the most relevant concerns in human health, with gastrointestinal infections being among the main illnesses that affect humans.
Among gastric problems, we have GASTRITIS AND GASTRIC ULCERS as the main public health problems. Gastritis and gastric ulcers normally result from inflammation and corrosion of the walls of the stomach (gastric mucosa) and are generally associated (caused) by the bacterium Helicobacter pylor, which, according to the literature, this bacterium settles on these walls (of the stomach) and starts to release urease that ends up altering the normal pH of the stomach (acid), which leads to inflammation and corrosion of the mucous membranes and consequent gastritis or ulcers, respectively.
In addition to bacterial infections, gastritis and gastric ulcers are associated with several factors, with emphasis on prolonged fasting, chemical substances including drugs, alcohol, foods with strong seasonings including chilli, which ends up causing inflammation of the stomach walls and/or corrosion. of the same, resulting in the appearance of wounds and consequent gastritis or ulcers, respectively.
Among patients with gastritis and/or ulcers, one of the dilemmas is associated with the foods to consume in order to minimize the sensation of pain and discomfort.
Summer is a time for fun in the sun, but the heat and humidity can also wreak havoc on your skin. From itchy rashes to unwanted pigmentation, several skin conditions become more prevalent during these warmer months.
1. Middle East Lecture Tour, 2012
Use of LH in IVF and IUI
Differences between rec-hLH and LH
Activity in HMG Preparations
Sandro Esteves, MD, PhD
Director, ANDROFERT
Center for Male Reproduction
Campinas, BRAZIL
2. What is in it for me?
Role of LH in Reproductive Cycles
LH window concept
To Whom to Give LH Supplementation
Recent Advances in Injectable
Gonadotropin Preparations
Rec-LH Products
Differences between rec-hLH and LH
Activity in HMG Preparations
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. Use of LH in IVF and IUI
Differences between rec-hLH and LH
Activity in HMG Preparations
Review this Lecture at:
http://www.androfert.com.br/review
Esteves, 4
5. What is in it for me?
Role of LH in Reproductive Cycles
2 To Whom to Give LH Supplementation
3
Recent Advances in Injectable
Gonadotropin Preparations
Rec-LH Products
Differences between rec-hLH and LH
Activity in HMG Preparations
Esteves, 5
6. • Mild Stimulation
(low dose rec-hFSH +
GnRH ant.):
Promotion of Steroidogenesis • 5 oocytes
(TCs) early FP retrieved;
• IR = 31%
• Adequate estrogen production
• Uterine/endometrial
changes
• Conventional
Stimulation :
Stimulation of final Follicular
Maturation (GCs) late FP • 10 oocytes
retrieved;
• IR = 29%
Verberg et al.
Esteves, 6
Esteves, 6 Alviggi et al.Hum Reprod Update 2009; 15: 5–12.
Reprod Biomed Online 2006;12:221.
8. Evidence for LH threshold (1)
Rec-hLH suppementation (UI): 0 25 75 225
3000
Serum Estradiol Levels
2500 225
2000
(pmol/L)
1500 75
1000
500
25
0 0
Day 1 Day 5 Day 10 hCG
Day of Stimulation
Esteves, 8 The European Recombinant Human LH Study Group, JCEM 1998; 83:1507
9. Evidence for LH threshold (2)
0 25 75 225 rLH
Endometrial Thickeness (mm) 75
8 Injected rLH LH Cmax
225
dose (UI)
6 75 UI 0.5 – 1.35 UI/L
4
25
2 0
0
Day 1 Day 5 Day 10 hCG
Day of Stimulation
Esteves, 9 The European Recombinant Human LH Study Group, JCEM 1998; 83:1507
10. • Suppression of GC proliferation
High •
• Mild Stimulation
Follicular atresia (non-dominant follicles) dose rec-hFSH +
(low
• Premature luteinization GnRH ant.):
• Oocyte development compromised
• 5 oocytes
CEILING retrieved;
Normal
• IR = 31%
• Normal androgen and estrogen biosynthesis
• Normal follicular growth and development
• Normal oocyte maturation
THRESHOLD • Conventional
Stimulation :
Low
• Insufficient androgen (and estrogen) synthesis
• 10 oocytes
• Follicular growth and maturation impaired
retrieved;
• Inadequate endometrial proliferation
• IR = 29%
Verberg et al.
Esteves, 10
Esteves, Balasch J, Fábreques F. Curr Opin Obstet Gynecol 2002, 14:265.
Hum Reprod Update 2009; 15: 5–12.
11. Both FSH and LH are essential for normal
estradiol biosynthesis.
75 UI recLH is sufficient to promote optimal
follicular and endometrial growth as well as
androgen production in most HH patients.
Evidence suggests that in reproductive cycles
optimal follicular development occurs within an
‘LH window’, above a certain ‘LH threshold’ and
below an ‘LH ceiling’ (1.2 to ? UI/L).
Esteves, 11
12. What is in it for me?
Role of LH in Reproductive Cycles
To Whom to Give LH Supplementation
Recent Advances in Injectable
Gonadotropin Preparations
Rec-LH Products
Differences between rec-hLH and LH
Activity in HMG Preparations
Esteves, 12
13. 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, 13 induction and ovarian stimulation. Hum Reprod Update 2008;14:1-14.
14. 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, 14
15. 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, 15 van Loendersloot et al. Hum Reprod Update 2010; 16: 577–589.
16. Normal
• ~80% normogonadotropic women 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 levels
(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, 16 RBMOnline 2009; 7. De Placido et al. Clin Endocrinol (Oxf) 2004;60:637;
17. 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, 17 Mochtar MH, Cochrane Database, 2007; Alviggi, et al. RBMOnline 2012
18. Theca cells
Increase in LH
LH drive
LH
Granulosa
Increase in cells
FSH drive FSH
Increasing the Number % Cycle Pregnancy
Level Stimulation Dose of oocytes cancellation rates
1b FSH… retrieved
Manzi et al, 1994 …is not associated with better
Klinkert et al, 2004 IVF outcome
Berkkanoglu & Ozgur,
2010
Esteves, 18
19. Reduced oocyte quality
Less Sensitive Ovaries
Reduced Fertilization Rate
Reduced Embryo Quality
Increase Miscarriage Rates
Westergaard et al., 2000; Esposito et
al., 2001; Humaidan et al., 2002
Reduced Androgen Decreased Reduced
ovarian LH receptor LH
secretory numbers of
paracrine poly- bioactivity
capacity functional
activity morphisms while
reduced LH
receptors imnuno-
• Piltonen et al.,
reactivity
Hurwitz & Alviggi et al., unchanged
Santoro 2004 2006 2003
• Vihko et al. 1996
• Mitchell et al.
1995; Marama et
al 1984
Esteves, 19
20. 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, 20 Hum Reprod Update 2012; 8(2):127-45. Hill MJ et al. Fertil Steril 2012; 97:1108-4.
21. Action of LH at the follicular level that increases
androgen production for its later aromatization to
estrogens in a dose dependent manner may
restore the follicular milieu in these patients to
recover oocyte quality and, therefore, embryo
quality and implantation rates.
Jamnongjit M et al. PNAS 2005;102:16257-16262
22. Level LH Supplementation in
1b
Hypo/Slow Responders (1)
• RCT 260 pts with “steady” response on COS D8
(E2 <180pg/mL; >6 follicles <10mm)
• 3 groups:
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, 22 De Placido et al. Hum Reprod. 2004; 20: 390-6.
23. Level
1b LH Supplementation in
Hypo/Slow Responders (2)
• RCT
• 126 pts. follicular stagnation during d7-d10 COS
• 4 groups:
Mean No. oocytes retrieved LBR (%)
41 37
22 18
8 11 11 10
increase in r- increase in r- increase in r- controls
hFSH dose hFSH dose + r- hFSH dose + LH
(max. 450UI) hLH (75-150UI) supplementation
supplementation with HMG
Esteves, 23 Ferraretti et al. Fertil Steril. 2004; 82: 1521-6.
24. Level LH Supplementation in
1b 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 et al., 2008.
Similar follicular development HMG vs FSH+rLH; higher
cumulative PR after 3 cycles in FSH+LH (56% vs 23%; p=0.01):
Carone et al., 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 et al., 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 et al., 2011.
Esteves, 24
25. 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?
Is LH needed in a GnRH antagonist Protocol?
FSH
LH
2:1? 1:1? Fixed? Mimic of
natural LH levels?
Esteves, 25
26. Level
Is LH needed in a GnRH
1a
antagonist Protocol?
Unselected women undergoing COS;
r-hFSH+r-hLH vs. r-hFSH alone in antagonist cycles
Mochtar et al. Kolibianakis et al. Baruffi et al.
3 RCT (N=216) 2 RCT (N=176) 5 RCT (N= 434)
Estradiol on WMD 571 - WMD 514
hCG day (pg/ml) (95% CI 259; 882) (95% CI 368; 660)
No. retrieved WMD 0.50 WMD 0.41
-
oocytes (95% CI -0.68; 1.68) (95% CI -0.44; 1.3)
†OR 0.79 *OR 0.86 †OR 0.89
CPR†/LBR*
(95% CI: 0.26; 2.43) (95% CI: 0.04; 1.85) (95% CI: 0.57; 1.39)
WMD weight mean difference
Mochtar MH et al. Cochrane Database Syst Rev. 2007;2:CD005070; Kolibianakis et al, Hum Reprod
Update. 2007;13:445-52; Baruffi RL et al, Reprod Biomed Online. 2007;14:14-25.
Esteves, 26
27. Level Is LH needed in a GnRH
1b antagonist Protocol?
RCT; 292 NG women aged 36-39; Fixed (D6) antagonist COH protocol
rFSH rFSH + rLH
P= 0.027
68%
61% OR=1.49
OR=1.56
95% CI 0.93-2.38
95% CI 1.04-2.33
33%
25% 27%
19%
%2PN Ongoing PR Implantation
Yes, for women aged >35 yo
Esteves, 27 Bosch et al. Fertil Steril. 2011; 95:1031-6.
28. Women with less sensitive ovaries (ovarian aging) have poorer
IVF outcomes.
Androgen secretory capacity decreases with ovarian ageing.
Mechanisms include decreased number of functional LH
receptors and ovarian paracrine activity resulting in reduced
LH bioactivity. LH-r polymorphisms possibly involved in hypo-
responders.
LH supplementation to COS is an evidence-based strategy to
maximize pregnancy results.
4 subgroups benefit of LH supplementation in COS:
Poor responders
Slow/hypo-responders
Age >35 years
Deeply suppressed endogenous LH levels
Esteves, 28
29. 3 subgroups clearly benefit of LH supplementation in
OI and IUI:
WHO group I anovulation
WHO group II clomiphene resistant
WHO group II with previous over-response to OS
Other potential indications include:
Poor responders
Slow/hypo-responders
Age >35 years
Deeply suppressed endogenous LH levels
Esteves, 29
30. What is in it for me?
Role of LH in Reproductive Cycles
To Whom to Give LH Supplementation
Recent Advances in Injectable
Gonadotropin Preparations
Rec-LH Products
Differences between rec-hLH and LH
Activity in HMG Preparations
Esteves, 30
33. • Same injection device
design for all
gonadotropins;
• Color-coded for
differentiation;
• Pre-filled, ready-to-
use family of pens for
fertility treatment.
Esteves, 33
34. 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 and rec-hLH
Bassett et al. Reprod Biomed Online 2005;10:169–177;
Esteves, 34 Driebergen et al. Curr Med Res Opin 2003;19:41–46.
35. Alfa Unit Beta unit Carboxyl terminal
(biological action segment
and receptor (determines half-life)
affinity)
LH 92 AA; 121 AA Absent; half life of 20’
hCG Identical to LH 144 AA Present; half-life of
Higher receptor affinity 24h
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, 35 ASRM Practice Committee. Fertil Steril. 2008; 90:S13-20.
36. Level
2a
• Matched case-control study;
• N=4,719 pts.; long GnRH-a protocol
• 3 groups
35
30 P=0.02 Duration of
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, 36 Buhler KF, Fisher R. Gynecol Endocrinol 2011; 1-6.
37. 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, 37
2004; 70:861-866; Grondal ML et al. Fertil Steril 2009; 91: 1820-1830.
38. Recombinants vs Urinary products
Recombinant LH preparations have 3 major
differences compared to urinary products:
Higher purity and specific activity (SC delivery in
very small volumes))
Higher dose precision (FbM)
LH activity in u-HMG is hCG dependent:
hCG is concentrated during purification or added to
achieve the desired amount of LH-like biological activity;
hCG has higher half-life and biological activity compared to
rec-hLH.
Esteves, 38
39. Differences between rec-hLH and LH
Activity in HMG Preparations
Lower expression of LH receptor gene
in pts. treated with HMG (LH-r down-
regulation).
Preparations used for COS are
important for granulosa cell function and
may influence the developmental
competence of the oocyte and the
function of corpus luteum.
Esteves, 39
40.
41. Use of LH in IVF and IUI
Progesterone Issues
Supplementary Material
Esteves, 41
42. Steroidogenesis During Normal
Follicular Phase and Following COS
The expression of LH-R (GCs) is linked to the synthesis of
progesterone during COS.
Levels of LH-R and progesterone synthesis vary depending on
the hormones used during the stimulation protocol.
Esteves, 42 Steroidogenesis Consensus Meeting III, Copenhagen, Denmark, May 2011.
43. Steroidogenesis in COS
Endogenous LH then results in higher levels of progesterone
synthesis following treatment with FSH than hMG:
higher levels of LHR expressed on granulosa cells and
increased number of granulosa cells.
Esteves, 43 Steroidogenesis Consensus Meeting III, Copenhagen, Denmark, May 2011.
44. Level
1a Progesterone on the Day of hCG
and Probability of Pregnancy in IVF
Progesterone Elevation x No Progesterone Elevation
Venetis et al, 2007 Kolibianakis et al, 2012
GnRH Agonists Antagonists Antagonists
analogue n = 2,624 n = 109 n = 109
OR: 0.86 OR: 0.57 WMD: -9%
CPR (95% CI: 0.59; 1.25) (95% CI: 0.09; 3.56) (95% CI: -17; -2)
E2 levels on
WMD: 413.06 WMD: 956
the day of (95% CI: 240.14; 585.99) (95% CI 248; 1664)
hCG (pg/mL)
Number of
WMD: +2.96 WMD: 0.00 WMD: +2.9
retrieved (95% CI: +1.74; +4.18) (95% CI: -2.98; +2.99) (95% CI: +1.5; +4.4)
oocytes
heterogeneity of the studies included;
arbitrary serum progesterone threshold values
Venetis et al, Hum Reprod Update. 2007;13:343-55;
Esteves, 44 Kolibianakis et al, Curr Pharm Biotechnol. 2012;13:464-70.
45. Level
2b Progesterone on the Day of hCG
and Probability of Pregnancy in IVF
Bosch et al. 2010 (N=4,032)
OPR: inversely associated with serum P levels on the day of hCG irrespective
of the GnRH analogue: CUT-OFF: 1.5 ng/mL
Serum P levels ≤1.5 ng/ml: ↑OPR
31% versus 19.1%; P = 0.00006;
OR: 0.53 (95% CI, 0.38 – 0.72)
positively
FSH dose
associated
No. oocytes with P levels
Estradiol (day of hCG) (P < 0.0001 for
all).
Serum P levels:
agonists: 0.84 ± 0.67 vs antagonists: 0.75 ± 0.66 (P = 0.0003)
Esteves, 45 Bosch et al. Hum Reprod. 2010; 25(8):2092-100.
46. Level
Progesterone on the Day of hCG
2b
and Probability of Pregnancy in IVF
Xu et al, 2012 (N=11,055 long agonist protocol)
For fresh cycles, OPR inversely associated with serum P levels on hCG day
FSH dose
Positively
No. oocytes associated
with P levels ■ Fresh
Estradiol (day of hCG)
■ FET
Serum P
Ovarian Number of
threshold
response oocytes
(ng/mL)
Poor ≤4 1.5
Intermediate 5-19 1.75
High ≥20 2.25
Xu et al. Fertil Steril 2012;97:1321–7.
Esteves, 46
47. Progesterone on the Day of hCG
and Probability of Pregnancy in IVF
The rise in progesterone levels seen during COS for
IVF/ICSI cycles cannot be explained by luteinization of
granulosa cells
Conversion
FSH activity Granulosa of cholesterol to
cell progesterone
LH Conversion
Teca
bioactivity of progesterone
cell
to androgens
FSH dose, number of follicles and rec-hFSH (x HMG):
correlation to P increase on hCG day
Bosch et al. Hum Reprod. 2010;25:2092-100;
Esteves, 47 Xu et al. Fertil Steril 2012;97:1321–7; Smitz J et al. Hum Reprod 2007;22:676–87.
48. LevelsProgesterone on the Day of hCG
2b, 3 and Probability of Pregnancy in IVF
Hofmann et al, Fertil Steril. 1993;60:675-9; Xu et al. Fertil Steril 2012;97:1321–7; Huang et al.
Fertil Steril 2012; 98:664–70; Melo et al. Hum Reprod 2006; 21:1503–1507.
Esteves, 48
49. Serum Progesterone and IVF Outcome
Most circulating P4 (95%) is produced in the intrafollicular
compartment by the granulosa cells;
Intrafollicular P4 and Hydroxi-progesterone are terminal
products and cannot be converted to estradiol by GCs
under the effect of LH/hCG activity contained in hMG, due to
lack of expression of an hydrogenase and P450-17α needed
for this pathway;
Higher serum Progesterone increments are related with
more follicles developed and more oocytes retrieved and it’s
effect in pregnancy still controversial. Increments up to
>7nmol/L seems not to affect clinical pregnancy rates.
50. Serum Progesterone and IVF Outcome
Treatment with FSH results in higher levels of
progesterone than treatment with hMG.
A large number of developing follicles leads to
increased levels of progesterone.
The higher the level of LH present, the higher the
level of progesterone.
The effect of high progesterone levels at the time
of hCG administration on pregnancy outcome is
still controversial. Further detailed analyses are
required to understand why, when and how much
progesterone is detrimental for implantation rates.
Esteves, 50