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
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 monitoring of the ART (assisted reproductive technology) cycle. It describes various methods for monitoring, including ultrasound to measure follicle growth and endometrial thickness, as well as using ultrasound combined with serum estradiol levels. The key objectives of monitoring are outlined, such as predicting ovarian response, monitoring pituitary suppression, evaluating gonadotropin dose, preventing OHSS, determining the optimal time for hCG administration, and avoiding cycle cancellation. Indicators for when to adjust gonadotropin dosage or cancel the cycle are provided. Ultrasound is identified as the most practical monitoring method and combining it with estradiol is particularly useful for high-risk patients.
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.
Current markers for ovarian reserve are AMH & Antral follicle counts. AMH levels have been used to stratify patients with respect to fertility & further used in appropriate treatment options for successful pregnancy in an infertile couple.
This document discusses luteal phase physiology following GnRH agonist (GnRHa) trigger versus HCG trigger for final oocyte maturation in IVF/ICSI cycles. It compares the differences in luteal steroid levels and LH activity between the two triggers. The safety and efficacy of GnRHa trigger is examined, including prevention of OHSS and effects on oocyte maturation and implantation. Limitations of GnRHa trigger in supporting the luteal phase are outlined, as well as various approaches to optimal luteal phase support, including exogenous steroids or stimulating endogenous support with low dose HCG or recombinant LH. The document concludes that with appropriate modified luteal phase support, reproductive outcomes after GnRHa trigger can
Polycystic ovary syndrome (PCOS) is the most common endocrine condition affecting 6-18% of adolescent girls. Diagnosing PCOS during adolescence is challenging due to overlapping features with normal puberty. This document provides guidelines for the diagnosis of adolescent PCOS, including evaluating irregular menstrual cycles, clinical or biochemical signs of hyperandrogenism, and excluding other conditions through investigations. Pelvic ultrasound is not recommended for diagnosis in those under 8 years post-menarche due to high rates of multifollicular ovaries in normal adolescents.
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
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 monitoring of the ART (assisted reproductive technology) cycle. It describes various methods for monitoring, including ultrasound to measure follicle growth and endometrial thickness, as well as using ultrasound combined with serum estradiol levels. The key objectives of monitoring are outlined, such as predicting ovarian response, monitoring pituitary suppression, evaluating gonadotropin dose, preventing OHSS, determining the optimal time for hCG administration, and avoiding cycle cancellation. Indicators for when to adjust gonadotropin dosage or cancel the cycle are provided. Ultrasound is identified as the most practical monitoring method and combining it with estradiol is particularly useful for high-risk patients.
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.
Current markers for ovarian reserve are AMH & Antral follicle counts. AMH levels have been used to stratify patients with respect to fertility & further used in appropriate treatment options for successful pregnancy in an infertile couple.
This document discusses luteal phase physiology following GnRH agonist (GnRHa) trigger versus HCG trigger for final oocyte maturation in IVF/ICSI cycles. It compares the differences in luteal steroid levels and LH activity between the two triggers. The safety and efficacy of GnRHa trigger is examined, including prevention of OHSS and effects on oocyte maturation and implantation. Limitations of GnRHa trigger in supporting the luteal phase are outlined, as well as various approaches to optimal luteal phase support, including exogenous steroids or stimulating endogenous support with low dose HCG or recombinant LH. The document concludes that with appropriate modified luteal phase support, reproductive outcomes after GnRHa trigger can
Polycystic ovary syndrome (PCOS) is the most common endocrine condition affecting 6-18% of adolescent girls. Diagnosing PCOS during adolescence is challenging due to overlapping features with normal puberty. This document provides guidelines for the diagnosis of adolescent PCOS, including evaluating irregular menstrual cycles, clinical or biochemical signs of hyperandrogenism, and excluding other conditions through investigations. Pelvic ultrasound is not recommended for diagnosis in those under 8 years post-menarche due to high rates of multifollicular ovaries in normal adolescents.
This document discusses individualized controlled ovarian stimulation (I COS) protocols. It notes that conventional approaches use long agonist protocols with standard gonadotropin doses based on age. I COS allows for personalization based on ovarian reserve tests, biomarkers, and other factors to customize stimulation aims at moderate oocyte retrieval while increasing clinical pregnancy rates. Prediction models can be used to determine starting doses, protocols, and adjuvants based on a patient's ovarian response classification as poor, normal, or hyper responders.
Dr. Kaberi Banerjee is a renowned fertility specialist in India. She has over 8000 IVF cases and has received several national and international awards for her work. She discusses medically complicated IVF patients who have medical disorders that can affect fertility or aggravate during treatment. These include hypertension, diabetes, heart disease, epilepsy, blood clots, endocrine disorders, cancers, lupus, HIV, and obesity. For each condition, she outlines how it impacts fertility, any pre-IVF preparation needed, and management during ovarian stimulation and pregnancy to optimize outcomes.
This document discusses recurrent implantation failure (RIF) after in vitro fertilization. It defines RIF and reviews its potential causes and treatments. The etiology of RIF may involve endometrial factors, gamete/embryo issues, or multifactorial causes. Investigations aim to identify specific causes, and treatments target the endometrium, embryos, or multiple contributing issues. While some interventions like hysteroscopy, endometrial injury, and blastocyst transfer have shown benefits, individualized, multidisciplinary care is needed given the complex, multifactorial nature of RIF.
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
Dr. Antima Rathore discusses the risks and genetic considerations of intracytoplasmic sperm injection (ICSI). ICSI was developed in 1992 and involves directly injecting a single sperm into an egg to facilitate fertilization. While ICSI has enabled many with male factor infertility to conceive, it may also carry increased risks of transmitting genetic defects from the sperm to offspring. The document reviews studies on potential increased risks of chromosomal abnormalities, imprinting disorders, inherited genetic disorders linked to male infertility, and congenital malformations in children conceived through ICSI. However, the evidence for many of these risks is still inconclusive or unclear whether the risks are due to the ICSI procedure itself or the underlying infertility issues of the
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.
Progesterone rise on the day of hcg administration (ppremature luteinization)...Aboubakr Elnashar
This document discusses premature luteinization (PL), defined as a rise in progesterone on the day of hCG administration in IVF. It outlines that the incidence of PL varies widely in studies from 13-71% due to different definitions and protocols. Several hypotheses for the pathogenesis of PL are presented, including elevated LH levels and increased LH receptor sensitivity. The impact of PL on IVF outcomes is controversial, with some studies finding negative effects and others no effect. The document concludes by recommending prospective studies are needed to better understand the role of progesterone elevation on IVF success rates and provides suggestions for preventing PL during treatment.
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.
This document discusses the management of Ovarian Hyperstimulation Syndrome (OHSS) in OI/IUI cycles. It begins with an overview of OHSS, noting its incidence, risk factors, pathogenesis involving vascular endothelial growth factor, and clinical classification. The document then discusses strategies for preventing OHSS, including identifying at-risk patients; using a mild ovarian stimulation protocol with low-dose gonadotropins; canceling cycles or using a GnRH agonist for final oocyte maturation instead of hCG; and administering intravenous colloids or dopamine agonists secondarily. The goal of management is to maximize treatment success while minimizing complications and risks like OHSS and multiple pregnancies.
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.
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.
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.
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.
Invited Lecture delivered by Dr Sujoy Dasgupta in National Youth Conference, held at Patna in August 2019. This session was sponsored by Bharat Serum and Vaccines
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 appears to be results from the 1st stage of the CPEF Over 35 National competition. It includes timing data for various checkpoints and stages for 3 competitors: Flavio Camara, Jairo Lins, and Shalton Frederico Pessoa. For each competitor it lists their start and finish times at each checkpoint and stage, as well as their maximum speeds, average speeds, and total times.
This document discusses individualized controlled ovarian stimulation (I COS) protocols. It notes that conventional approaches use long agonist protocols with standard gonadotropin doses based on age. I COS allows for personalization based on ovarian reserve tests, biomarkers, and other factors to customize stimulation aims at moderate oocyte retrieval while increasing clinical pregnancy rates. Prediction models can be used to determine starting doses, protocols, and adjuvants based on a patient's ovarian response classification as poor, normal, or hyper responders.
Dr. Kaberi Banerjee is a renowned fertility specialist in India. She has over 8000 IVF cases and has received several national and international awards for her work. She discusses medically complicated IVF patients who have medical disorders that can affect fertility or aggravate during treatment. These include hypertension, diabetes, heart disease, epilepsy, blood clots, endocrine disorders, cancers, lupus, HIV, and obesity. For each condition, she outlines how it impacts fertility, any pre-IVF preparation needed, and management during ovarian stimulation and pregnancy to optimize outcomes.
This document discusses recurrent implantation failure (RIF) after in vitro fertilization. It defines RIF and reviews its potential causes and treatments. The etiology of RIF may involve endometrial factors, gamete/embryo issues, or multifactorial causes. Investigations aim to identify specific causes, and treatments target the endometrium, embryos, or multiple contributing issues. While some interventions like hysteroscopy, endometrial injury, and blastocyst transfer have shown benefits, individualized, multidisciplinary care is needed given the complex, multifactorial nature of RIF.
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
Dr. Antima Rathore discusses the risks and genetic considerations of intracytoplasmic sperm injection (ICSI). ICSI was developed in 1992 and involves directly injecting a single sperm into an egg to facilitate fertilization. While ICSI has enabled many with male factor infertility to conceive, it may also carry increased risks of transmitting genetic defects from the sperm to offspring. The document reviews studies on potential increased risks of chromosomal abnormalities, imprinting disorders, inherited genetic disorders linked to male infertility, and congenital malformations in children conceived through ICSI. However, the evidence for many of these risks is still inconclusive or unclear whether the risks are due to the ICSI procedure itself or the underlying infertility issues of the
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.
Progesterone rise on the day of hcg administration (ppremature luteinization)...Aboubakr Elnashar
This document discusses premature luteinization (PL), defined as a rise in progesterone on the day of hCG administration in IVF. It outlines that the incidence of PL varies widely in studies from 13-71% due to different definitions and protocols. Several hypotheses for the pathogenesis of PL are presented, including elevated LH levels and increased LH receptor sensitivity. The impact of PL on IVF outcomes is controversial, with some studies finding negative effects and others no effect. The document concludes by recommending prospective studies are needed to better understand the role of progesterone elevation on IVF success rates and provides suggestions for preventing PL during treatment.
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.
This document discusses the management of Ovarian Hyperstimulation Syndrome (OHSS) in OI/IUI cycles. It begins with an overview of OHSS, noting its incidence, risk factors, pathogenesis involving vascular endothelial growth factor, and clinical classification. The document then discusses strategies for preventing OHSS, including identifying at-risk patients; using a mild ovarian stimulation protocol with low-dose gonadotropins; canceling cycles or using a GnRH agonist for final oocyte maturation instead of hCG; and administering intravenous colloids or dopamine agonists secondarily. The goal of management is to maximize treatment success while minimizing complications and risks like OHSS and multiple pregnancies.
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.
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.
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.
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.
Invited Lecture delivered by Dr Sujoy Dasgupta in National Youth Conference, held at Patna in August 2019. This session was sponsored by Bharat Serum and Vaccines
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 appears to be results from the 1st stage of the CPEF Over 35 National competition. It includes timing data for various checkpoints and stages for 3 competitors: Flavio Camara, Jairo Lins, and Shalton Frederico Pessoa. For each competitor it lists their start and finish times at each checkpoint and stage, as well as their maximum speeds, average speeds, and total times.
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.
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.
2. Overin fizyolojik görevi oositlerin periyodik olarak atılması ve
steroid hormonlar olan östradiol ve progesteron üretimidir.
Her iki aktivitede sürekli tekrarlayan folliküler olgunlaşma
,ovulasyon ,korpus luteum oluşumu ve gerilemesi fonksiyonları
sonucunda oluşur.
3. Asıl metin stillerini düzenlemek için tıklatın
İkinci düzey
Üçüncü düzey
Dördüncü düzey
Beşinci düzey
4. Overler büyüme hormonlarının etkisine bağlı olarak fonksiyon
ve büyüklüğü artan ve azalan organlardır .
5. Gestasyonun 8 .haftasında başlayan germ hücrelerinin mitotik
çoğalması 16-20.haftada maksimum düzeye ulaşır(6-7 milyon
oogonia).
Bu dönemden sonra germ hücreleri genlerle regüle edilen
apopitotik bir azalma sürecine girer.Doğumda germ hücre sayısı
1-2 milyona, puberte başlangıcında ise 300-500 bine düşer .
Reproduktif dönemde primordial folliküllerdeki azalma her ay
yaklaşık 1000 follikül şeklinde sabitlenir.
6. Reproduktif dönemde her ay bir grup primordial folikül
maturasyon ve ovulasyon için uyarılmaktadır.Dinlenme
durumundaki primordial foliküllerin matur oosit haline erişme
süreci uzun bir dönemdir.Yaklaşık olarak üç menstrüel siklus
uzunluğundadır.
Bu süreç esnasında bir kısım foliküller seçilerek ovulasyona
ilerler büyük bir kısmı ise atrezi uğrar.
7. Asıl metin stillerini düzenlemek için tıklatın
İkinci düzey
Üçüncü düzey
Dördüncü düzey
Beşinci düzey
8. Folikülogenezis hayat boyu devam eden bir dinamik
süreçtir.Tüm fizyolojik koşullarda , çocukluk döneminden
menapoza kadar devam eder.
9. Otuzlu yaşlarda fekundite kademeli olarak azalır. Yaklaşık
olarak 38 li yaşlarda, overlerde 25 bin oositin kaldığı
zamanlarda fertilitede belirgin bir düşme başlar. Menopoz
döneminde follikül sayısı 1000 in altındadır.
Folliküllerdeki kayıp hızı genetik olarak anneden kızına
aktarılan ailevi eğilim ile belirlenmektedir.
10. Over rezervi
Ovarian korteksteki primordial follikül sayısı ve oosit kalitesi ile
belirlenen üreme potansiyelini ifade eder.
Over rezervinin doğumdan itibaren azaldığı ve belirli follikül
sayısına sahip kadınların yıllar içerisinde yaşın ilerlemesi ile
birlikte bu rezervi sürekli yitirdikleri bilinmektedir.
11. Over Rezervini Değerlendirme Neden Önemli?
İnfertilite öyküsü olan ve bu nedenle tedavi planlanan
hastalarda,hastanın over rezervi hakkındaki bilgi
bireyselleştirimiş bir ovulasyon planı yapmakta ve ovarian
hiperstimulasyon riskini azaltmakda önemlidir.
Over yetmezliğini öngörmede kullanılır.
Kemoterapi yada radyoterapi öyküsü olan kadınlarda fertilite
kapasitesini değerlendirmede kullanılır.
12. Over Rezervini Olumsuz Yönde Etkileyen Faktörler
Yaş
Obesite
Medikal nedenler;
Geçirilmiş over cerrahisi ,tek over ,sigara, kemoterapi ve radyoterapi,
tip1 DM, şiddetli endometriozis
13. Otoimmun nedenler;
Tiroit otoimmun hastalıklar
Genetik nedenler ;
Prematur menapoz aile öyküsü, X kromozomu bozuklukları,
İlgili gen polimorfizmleri (östradiol sentez ve metabolizmasıyla ilgili
bozukluklar, AMH ve AMH reseptör genleri vb.)
14. Klinik Kullanımda Olan Over Rezerv Testleri
Yaş faktörü
Histolojik testler: Over biopsisi
Endokrin testler
Ultrasonografik testler
18. Yaş Faktörü
Kadının yaşının artması ile fertilite azalmakta; özellikle 35
yaşından itibaren oosit sayı ve kalitesinde progresif bir
azalma olduğu bilinmektedir.
Oosit havuzundaki azalmaya bağlı olarak azalan östrojen ve
inhibin sekresyonundan kaynaklanan FSH artışı yaşla
beraber fertilite azalmasının göstergesidir.
İleri yaştaki kadınlarda ART ile elde edilen oositlerde çeşitli
morfolojik değişiklikler izlenmektedir.
Oositlerdeki sayısal kayıp ile birlikte gözlenen niteliksel
değişikliklerin mekanizması net olarak açıklanamamakla
birlikte çeşitli görüşler öne sürülmektedir.
19. Yaşla birlikte oositlerde görülen değişiklikler sitoplazmik ve nükleer
yapılarda görülmektedir.
Tipik olarak genişlemiş perivitellin aralık,perivitellin debri ve ince
zona pellusida izlenmektedir. Artmış oksidatif stress mitikondrial
DNA delesyonları ve oositlerde DNA fragmantasyon artışı bu
değişikliklerin en önemlileridir.
Ayrıca ileri yaştaki kadınların oositleri ile gerçekleştirilen IVF ve
ICSI uygulamalarında elde edilen embriyolarda yüksek anöploidi
görülmektedir.
20. Ovarian yaşlanma oosit sayı ve kalitesindeki azalmanın bir
sonucudur.Oosit sayısındaki azalma doğumdan önce başlar
pubertede devam eder. Reproduktif dönemde aylık maturasyon ve
ovulasyona sekonder olarak azalma hızlanır.
Oosit ve folikül sayısındaki bu azalma gebelik ve emzirme
döneminde ,oral kontraseptif kullanılan dönemlerde de devam eder.
21. Şek. 1. Kadında normal reproduktif yaşlanmanın evreleri.
Reprinted from Fertility and Sterility, 76 (5), Soules MR, Sherman S, Parrott E,
Rebar R, Santoro N, Utian W, et al, Executive summary: Stages of Reproductive
Aging Workshop (STRAW), page 875, 2001
22. Over Reserv Testi Olarak Yaş Faktörü Neden
Yeterli Değil?
Reproduktif yaşlanmadan dolayı fekundabilitede görülen azalma
puberte,fertil dönem,subfertilite ,menapozal geçiş ve menapoz şeklinde
devam eden doğal bir sürecin sonucudur.
Kronolojik yaş reproduktif evrenin sonuçlarını öngörmede çoğunlukla göz
önünde bulundurulur.Ancak kronolojik olarak aynı yaştaki kadınlarda
reproduktif potansiyel belirgin olarak farklı olabilir.
Aynı kronolojik yaştaki kadınlarda görülen bu farklılık bireysel olarak
ovarian yaşın farklılık göstermesinden dolayıdır.
Genetik faktörler reproduktif yaşlanmada önemli rol oynar.
24. Erken Foliküler Fazda FSH
Adetin 2-3. günü FSH nın over rezervi için bir belirteç
olarak bakılması 1980 li yıllardan bu yana
kullanılmaktadır.
İlerlemiş kadın yaşı yavaş ve sabit kompansatuar bir
FSH yükselmesi ile ilişkilidir.
Overlerden folikül gelişimini uyaran FSH nın kan düzeyi
over cevabı azaldıkça daha yüksek uyarıda bulunmak
için giderek yükselecektir.
25. Serum FSH seviyeleri nisbeten pahalı olmayan kitlerle
kolaylıkla ölçülebilir ancak kabul edilen üst sınır
laboratuvarlara ve kullanılan kitlere göre farklılık
gösterebilir.
Bu değerlendirmenin güvenilir biçimde yapılabilmesi için
her merkezin kendi laboratuvarının üst sınırını dikkate
alması ve sonuçların buna göre yorumlanması
gerekmektedir.
26. Üçüncü gün FSH değeri ≥ 10 IU/l saptanan olgularda
overin indüksiyona verdiği cevabın zayıf olduğu
bilinmektedir.
FSH değeri ≥ 15 IU/l saptandığında gebelik elde etme
şansının düşük olduğu bilinmektedir.
FSH değeri ≥20 IU/l olan vakalarda nadir olarak gebelik
elde edilmekle birlikte bu olgularda abortus riski çok
yüksektir.
27. FSH nın sirkadiyen ritminin oması , pulsatil salınımı ve
izoformlarındaki dalgalanmalar elde edilen sonuçlarda
potansiyel hatalara neden olabilir.
Persistan bazal FSH yüksekliği azalmış over rezervi ile koreledir
ancak bazı kadınlarda bazal FSH değerindeki geçici yükseklik
primordial folikül havuzu ile ilişkili değildir.
Aylık bazal FSH seviyelerindeki farklılık artmış progesteron ve
düşük östradiol düzeyi ile birlikte persiste korpus luteumdan
dolayı ortaya çıkabilir.
28. EFF de düşük FSH seviyeleri yeterli siklik luteolizisi
takiben normal bir hipotalamik-hipofizer-ovaryan-
uterin aksı gösterir.
Amenoreik kadınlarda bazal FSH seviyelerinin
değerlendirildiği güncel bir sistematik derlemede FSH
değeri -çok yüksek değerlerde- kötü over yanıtını
öngörmede yeterince doğru sonuç verdiği
gösterilmiştir*.
* Broekmans FJ, Kwee J, Hendriks DJ, et al. A systematic review of tests predicting
ovarian reserve and IVF outcome. Hum Reprod Update 2006; 12:685–718.
29. Erken Foliküler Fazda Östradiol
Estradiol granuloza hücrelerinden salgılanan steroid bir
hormondur.
Yapılan çalışmalarda östradiyolun IVF sonuçları
açısından düşük prediktif değere sahip olduğu
gösterilmiştir ancak son derece yüksek D3 östradiol
seviyeleri (>75 pg/ml) düşük gebelik oranları ve IVF de
düşük cevap ile ilişkilidir*.
* Tests for ovarian reserve: reliability and utility. Thaı´s S. Dominguesa, Andre´
M. Rochaa and Paulo C. Serafini Current Opinion in Obstetrics and Gynecology
2010, 22:271–276
30. Ancak önceki siklustan kalan persiste kistik bir
yapı da östradiolun yüksek ölçülmesine neden
olabilir.
Bu nedenle D3 östradiol seviyeleri ovaryan
rezervi değerlendirmede yaralı olmasa da bir
ovulasyon indüksiyonunun iptal edilip
edilmeyeceğini gösterebilir.
31. Erken Foliküler Fazda İnhibin B
İnhibin A ve B subünitelerinden oluşan heterodimerik bir
glikoproteindir.
İnhibin-B; preantral ve antral foliküllerdeki granuloza
hücrelerinden salgılanır. İnhibin B FSH salınımını
baskılar.
Serum inhibin-B seviyeleri yaşla birlikte azalır.
32. İnhibin-B over rezervinden ziyade over fonksiyonunun
değerlendirilmesinde geniş kabul görmüştür*.
İnhibin-B <45 pg/ml olması gonadotropinlere zayıf over
cevabı, yüksek IVF siklus iptali, elde edilen düşük oosit sayısı
ve azalmış gebelik oranları ile ilişkilidir.
Sonuç olarak İnhibin-B yaşla birlikte kademeli olarak azalmaz,
azalmış folikül havuzun oldukça geç bir belirtecidir.
*Knauff EA, Eijkemans MJ, Lambalk CB, et al. Anti-Mullerian hormone,
inhibin B, and antral follicle count in young women with ovarian failure. J Clin
EndocrinolMetab 2009; 94:786–792.
33. Anti Müllerian Hormon
AMH hücre büyümesinde ve farklılaşmasında önemli
olan TGF-ß ailesinde dimerik bir glikoproteindir.
Antral ve preantral foliküllerin granuloza hücrelerinden
salgılanır ve foliküllerin FSH ya duyarlılıklarını azaltır.
FSH bağımlı foliküler gelişimi inhibe ederek dominant
folikülün gelişimini sağlar.
Primordiyal folikül gelişimini engelleyerek primordiyal
folikül havuzundaki azalmayı önler.
34. Doğumda serum AMH seviyeleri çok zor tesbit
edilebilir, pubertede yüksek seviyelere ulaşır.
Yaşla birlikte kademeli olarak azalan AMH düzeyi
menapozda ölçülemez hale gelir.
AMH sekresyonu ovaryan siklustan bağımsızdır.
Diğer parametrelerden farklı olarak siklus içinde
düşük oranda değişiklik gösteren en iyi hormonal
belirteç olarak görülmektedir*.
1.Visser J. Role of anti-Mullerian hormone in follicle recruitment and maturation. J
Gynecol Obstet Biol Reprod (Paris) 2006; 35:2S30–32S34.
2. La Marca A, Sighinolfi G, Radi D, et al. Anti-Mullerian hormone (AMH) as a
predictive marker in assisted reproductive technology (ART). Hum Reprod
Update 2009; 16:113–130.
35. 0,5 ng/ml den daha yüksek AMH değerleri iyi over
rezervinin göstergesidir.Daha düşük değerler azalmış
over rezervini gösterir.0,15 ng/ml den daha düşük
değerler IVF de kötü yanıtı destekler.
37. Klomifen Sitrat Challange Test (CCCT)
Menstruasyonun 3. günü FSH ve E2 ölçümü yapılır,
takiben 5-9 günleri arasında 100 mg klomifen sitrat
uygulanır.
FSH ve E2 ölçümü 10. günde tekrarlanarak sonuçlar 3.
gündeki bazal değerlerle kıyaslanır.
38. Klomifen sitrat uyarısı ile folikül gelişiminin uyarılması,
buna bağlı olarak foliküllerden E2 salgılanması ve artan
E2 nin ise FSH yı baskılaması beklenir.
Onuncu günde FSH nın bazal değerlere göre artmış
olması(26 IU/L )veya E2 değerlerinde anlamlı bir
yükselme olmaması olumsuz bir sonuç olarak
değerlendirilir.
39. GnRH Analoğu Stimulasyon Testi (GAST)
GnRH agonistleri uygulamanın ilk 4-6 günleri
arasında FSH ve LH artışına ve buna bağlı olarak
da E2 artışına neden olur.
Testte siklusun 3. günü GnRH analoğu
uygulamasını takiben gözlenen E2 değişiklikleri
değerlendirilmektedir.
GAST sonrasında 4 farklı E2 paterni izlenebilir:
40. 1. Hızlı E2 yükselmesi, sonra siklusun 4. günü azalma
2. Gecikmiş E2 yükselmesini takibe siklusun 6. günü
azalma
3. Devamlı E2 yükselmesi
4. E2 yükselişinin olmaması
41. GAST ın over rezervini belirlemek açısında diğer teslere
üstünlüğü yoktur.
Uygulamadaki zorluk ve pahalı bir test olması nedeniyle
pratik kullanımda yer almamıştır.
42. Egzojen Fsh Ovarian Rezerv Testi (EFORT)
Siklusun 3. günü 300 IU FSH uygulamasından 24 saat
sonra östradiol ve inhibin B seviyelerindeki değişikliğin
ölçümüne dayanır.
Düşük veya gecikmiş cevap azalmış over rezervini
gösterir.
44. Antral Folikül Sayımı
Antral follikül sayımı; erken folliküler fazda 10mm den küçük
foliküllerin tvusg ile tespit edilmesidir.Adetin 2-4. günleri
arasında 4-10 AF olması iyi over rezervini gösterir.
AFC ovaryan yaşlanmanın ultrasonografik bir belirtecidir.
ART de düşük AFC (4-6 dan daha az) zayıf ovaryan yanıt ile
ilişkilidir.
Cutt-of değer 6 olarak belirlendiğinde AFC %40 sensitivite ve
%95 spesifiteye sahiptir,%90 oranında doğruluk oranı
mevcuttur.Bir IVF protokolünde AFC değeri 6 nın altında
olduğunda %75 oranında indüksiyona kötü yanıt görülür.
45. AFC over rezervini ve indüksiyona over cevabını
göstermede iyi bir prediktif değere sahiptir.Ancak oosit
kalitesini ve gebelik sonuçlarını öngörmede zayıf
prediktif değere sahiptir.
46. Over Volumü
Ovarian volüm kadın hayatının her on yılında belirgin olarak
azalır.Menapozda dramatik bir azalma olur.
Ovarian volum üç yönde ölçüm alınarak hesaplanır.
(KalınlıkxGenişlik xUzunluk)
Over boyutları erken folliküler fazda ölçülmelidir.
Over boyutlarını ölçerken ölçüme overdeki kist ve büyük folliküller dahil
edilmemelidir.Birçok çalışmada en fazla 15 mmlik folliküller ölçüme
dahil edilmiştir.
47. Over volümünün 3 cm küpten daha az ölçüldüğü durumlarda
(çok küçük over volümü) IVF sikluslarında daha az follikül ve
oosit elde edilmiştir.
Over volum ölçümü; geçirilmiş over cerrahisi,persiste follikül
kistleri,ovarian tümör varlığı,polikistik over gibi nedenlerden
etkileneceğinden dolayı prediktif değeri zayıftır.
48. Ovarian Stromal Kan Akımı
Ovarian arter direnci yüksek serum östrojen düzeyine bağlı
olarak dominant folikülün gelişeceği overde folliküler fazda
azalır.Dirençteki azalma ovulasyonda belirginleşir.Yaklaşık
beş gün değişmez.Sonrasında yavaşça artmaya başlar.
Çalışmalarda en az bir overde bozulmuş bazal stromal kan
akımının azalmış over rezervi ile ilişkli olduğu gösterilmiştir.
49. Ovarian Yetmezlik Durumu İçin Tarama Testlerinin Kombinasyonu
Tek bir test over reservini belirlemede yetersiz olduğundan değişik
testlerin kombinasyonu kullanılmaktadır.
2 siklus d3 FSH ölçümü ile beraberinde d10 inhibin-B
değerlendirilmesinin , Hendriks et al. ,ovarian reservi belirlemede
%71 sensitivite,%98 spesifitesi olduğu belirtilmiştir.
D 3 FSH, basal inhibin-B and antral follicle sayımının %75
sensitivite,%95 spesifitesi gösterilmiştir.Fakat bu testlerin yaşla ilgili
değişiklik göstermesi büyük sorunlardandır.