Dr. Geoffrey Sher on April 7, 2017 at 1:12 pm

Hi Andra,

It sounds as if you were a “high responder, possibly at risk of developing OHSS. In such cases, the protocol used for ovarian stimulation as well as the timing and trigger used could, in my opinion, profoundly affect egg development and chromosomal integrity. You need to know that just because there were many “mature ” eggs, does not mean that they were euploid (chromosomally competent).I would be interested to know the exact protocol used and whether a reduced dosage of hCG was used for the trigger, Ovidrel 500mcg or an agonist such as Lupron as this would make a difference to egg competency, in my opinion.

Severe Ovarian hyperstimulation syndrome (OHSS) is often associated with e poor egg/embryo quality. This is especially so in women with high ovarian LH-induced testosterone (e.g. those with PCOS). The often present with poorly developed (“dysmorphic”) eggs, with reduced fertilization potential and yielding “poor quality embryos”. However, in the author’s opinion (which admittedly runs contrary to popular opinion), this is unlikely to be due to an intrinsic deficit in egg quality. Rather, it more likely relates to intra-ovarian hormonal changes brought about by hyperstimulation and which compromise egg development. This effect, in my opinion, can often be significantly reduced through implementation of an individualized or customized ovarian stimulation protocols that minimize exposure of the developing follicles and eggs to excessive LH-induced ovarian androgens. This can be best achieved by limiting the use of LH-containing gonadotropins such as Menopur through selective institution of “prolonged coasting” (see below). Approaches to preventing OHSS include:
1.PROLONGED COASTING (My preferred approach) : My approach is to use a long pituitary DR protocol coming off up to 2 months on the BCP, overlapped in the last 3 days with the agonist, Lupron. The BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen (predominantly, testosterone) production and release. I then stimulate with low dosage FSHr (Follistim/Gonal-F/Puregon) to which I add a smidgeon of LH/hCG (Luveris/Menopur) from the 3rd day. Then, starting on day 7 of ovarian stimulation, I perform serial blood estradiol (E2) and ultrasound follicle assessments, watching for the # of follicles and [E2]. If there are > 25 follicles, I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. At this point, provided the [E2] reaches at least >2,500pg/ml, I stop the agonist as well as gonadotropin stimulation and track the blood E2 (without continuing US, follicle measurements) ) daily. The [E2] will almost invariably increase for a few days. I watch the E2 rise (regardless of how high a blood concentration it reaches) and then track it coming down again. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer a “trigger” shot of 10,000U hCGu (Profasi/ Novarel/Pregnyl) or hCGr (Ovidrel/Ovitrel-500mcg) and perform an egg retrieval 36 hours later. ICSI is a MUST because “coasted” eggs usually have no cumulus oophoris envelopment and eggs without a cumulus will not readily fertilize naturally. Moreover, they also tend to have a “hardened” envelopment (zona pellucida), making spontaneous fertilization problematic in many cases. All fertilized eggs are cultured to blastocyst (up to 6 days) and are then either vitrified and preserved for subsequent transfer in later hormone replacement cycles or up to two (2) fresh blastocysts are transferred transvaginal under US guidance.. The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If you start too early, follicle growth will stop and the cycle will be lost. If you start too late, you will encounter too many post-mature/cystic follicles (>22mm) that usually harbor abnormally developed eggs. Use of “Coasting” avoids unnecessary cycle cancellation, severe OHSS, and optimizes egg/embryo quality. The worst you will encounter is mild to moderate OHSS and this too is uncommon. The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC).
2.MULTIPLE FOLLICLE ASPIRATION: In some cases, where because of mean follicle size exceeding 16mm or when “coasting” fails to effectively lower the [E2} below 2,500pg/ml within 3 days, the number of developing follicles can effectively and drastically reduced through target transvaginal aspiration, 1-3 PRIOR to planned the hCG trigger. This will almost invariably be accompanied by a rapid and significant drop in the plasma [E2] and in the process will drastically reduce reduce the risk of OHSS occurring without significantly compromising egg/embryo quality. The drawback of this effective approach is the fact that it interjects an additional surgical intervention into an already complex and stressful situation. i
3.TRIGGERING WITH LOW DOISAGE hCG; Because of the fact that hCG augments the development of OHSS (unless preceded by “coasting”), may RE’s prefer to use a lower dosage of hCG for the “trigger. This is either done by administering 5,000U (half the traditional dosage) or by administering, a 250mcg (rather than 500mcg) of DNA recombinant form of hCGr (Ovidrel/Ovitrel. Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the “trigger” dosage of hCG administered (from 10,000U to 5,000U or 250mcg of recombinant hCG-Ovidrel) in the hope that by doing so the risk of critical OHSS developing will be lowered. While this might indeed be true, it is my opinion, that such a reduced dosage is usually insufficient to optimize the efficiency of egg meiosis, e3specially when there are so many follicles present. While the use of a reduced “trigger” dosage of hCG does indeed reduce the risk and occurrence of OHSS-related life-endangering complications, the price to be paid is reduced egg quality/”competency”.
4.“TRIGGERING” WITH A GnRH AGONIST (E.G. “LUPRON/BUSERELIN): More recently, an increasing number of RE’s prefer to trigger meiosis by way of an agonist (Lupron/Buserelin/Superfact () “trigger” rather than through the use of hCG. The idea is to mimic what happens in natural cycles to promote egg maturation (meiosis) and ovulation, namely to have the agonist cause a “surge” in the release of body’s own pituitary LH to trigger egg meiosis (maturation) .But the amount of LH released in by the pituitary gland is often insufficient to optimize meiotic egg maturation and thus, while this approach also lowers the risk of OHSS it again comes at the expense of egg quality/competency.

I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
•The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
•Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
•IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
•The Fundamental Requirements For Achieving Optimal IVF Success
•Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
•Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
•Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
•A personalized, stepwise approach to IVF
•Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting.
•“Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
•The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
•Email: Julied@sherivf.com
•Phone: 702-533-2691
?800-780-7437

Geoff Sher

I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

19,771 Comments

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amenda on April 7, 2017 at 12:49 pm

dear dr sher
in IVF how many days do i have to wait since 3 day transfer to check with home pregnancy test. i have early response pregnancy test and it is 10 days past my transfer.
- Dr. Geoffrey Sher on April 7, 2017 at 1:05 pm
  
  12 days.
  
  Geoff Sher
melanie on April 7, 2017 at 12:45 pm

Dear Dr Sher,
i have 7 embryos frozen in Cyprus (3 from own eggs and 4 from donor eggs) where I did several IVF treatments. i am now doing IVF in the USA and wondered if there are any regulations in getting embryos sent to a US clinic?
- Dr. Geoffrey Sher on April 7, 2017 at 1:05 pm
  
  Indeed there are. suggest you discuss this with the IVF program you are sourcing in the U>S.A.
  
  Geoff Sher
Andra on April 7, 2017 at 12:26 pm

I am 40 and started treatment 2 years ago. I’ve had 3 retrieval cycles. First one had 43 eggs (39 mature), second had 16 eggs (12 mature), third had 26 eggs (16 mature). Out of those more than 95% fertilized and I ended up with a total of 6 PGS passes embryos. None of them implanted. For this next retrieval, my dr put my on a month of birth control before my stim cycle. He did not include lupron. I’m concerned that my number of eggs will be greatly reduced this time around. I’m also concerned that he’s addressing egg issues but not looking at anything new to address the implantation issue. What are your thoughts.
- Dr. Geoffrey Sher on April 7, 2017 at 1:12 pm
  
  Hi Andra,
  
  It sounds as if you were a “high responder, possibly at risk of developing OHSS. In such cases, the protocol used for ovarian stimulation as well as the timing and trigger used could, in my opinion, profoundly affect egg development and chromosomal integrity. You need to know that just because there were many “mature ” eggs, does not mean that they were euploid (chromosomally competent).I would be interested to know the exact protocol used and whether a reduced dosage of hCG was used for the trigger, Ovidrel 500mcg or an agonist such as Lupron as this would make a difference to egg competency, in my opinion.
  
  Severe Ovarian hyperstimulation syndrome (OHSS) is often associated with e poor egg/embryo quality. This is especially so in women with high ovarian LH-induced testosterone (e.g. those with PCOS). The often present with poorly developed (“dysmorphic”) eggs, with reduced fertilization potential and yielding “poor quality embryos”. However, in the author’s opinion (which admittedly runs contrary to popular opinion), this is unlikely to be due to an intrinsic deficit in egg quality. Rather, it more likely relates to intra-ovarian hormonal changes brought about by hyperstimulation and which compromise egg development. This effect, in my opinion, can often be significantly reduced through implementation of an individualized or customized ovarian stimulation protocols that minimize exposure of the developing follicles and eggs to excessive LH-induced ovarian androgens. This can be best achieved by limiting the use of LH-containing gonadotropins such as Menopur through selective institution of “prolonged coasting” (see below). Approaches to preventing OHSS include:
  1.PROLONGED COASTING (My preferred approach) : My approach is to use a long pituitary DR protocol coming off up to 2 months on the BCP, overlapped in the last 3 days with the agonist, Lupron. The BCP is intended to lower LH and thereby reduce stromal activation (hyperthecosis) in the hope of controlling ovarian androgen (predominantly, testosterone) production and release. I then stimulate with low dosage FSHr (Follistim/Gonal-F/Puregon) to which I add a smidgeon of LH/hCG (Luveris/Menopur) from the 3rd day. Then, starting on day 7 of ovarian stimulation, I perform serial blood estradiol (E2) and ultrasound follicle assessments, watching for the # of follicles and [E2]. If there are > 25 follicles, I keep stimulating (regardless of the [E2] until 50% of all follicles reach 14mm. At this point, provided the [E2] reaches at least >2,500pg/ml, I stop the agonist as well as gonadotropin stimulation and track the blood E2 (without continuing US, follicle measurements) ) daily. The [E2] will almost invariably increase for a few days. I watch the E2 rise (regardless of how high a blood concentration it reaches) and then track it coming down again. As soon as the [E2] drops below 2500pg/ml (and not before then), I administer a “trigger” shot of 10,000U hCGu (Profasi/ Novarel/Pregnyl) or hCGr (Ovidrel/Ovitrel-500mcg) and perform an egg retrieval 36 hours later. ICSI is a MUST because “coasted” eggs usually have no cumulus oophoris envelopment and eggs without a cumulus will not readily fertilize naturally. Moreover, they also tend to have a “hardened” envelopment (zona pellucida), making spontaneous fertilization problematic in many cases. All fertilized eggs are cultured to blastocyst (up to 6 days) and are then either vitrified and preserved for subsequent transfer in later hormone replacement cycles or up to two (2) fresh blastocysts are transferred transvaginal under US guidance.. The success of this approach depends on precise timing of the initiation and conclusion of “prolonged coasting”. If you start too early, follicle growth will stop and the cycle will be lost. If you start too late, you will encounter too many post-mature/cystic follicles (>22mm) that usually harbor abnormally developed eggs. Use of “Coasting” avoids unnecessary cycle cancellation, severe OHSS, and optimizes egg/embryo quality. The worst you will encounter is mild to moderate OHSS and this too is uncommon. The obvious remedy for these adverse effects on egg and endometrial development is to employ stimulation protocols that limit ovarian over-exposure to LH and allowing the time necessary for the follicles/eggs to develop optimally, prior to administering hCG through the judicious implementation of “Prolonged coasting” (PC).
  2.MULTIPLE FOLLICLE ASPIRATION: In some cases, where because of mean follicle size exceeding 16mm or when “coasting” fails to effectively lower the [E2} below 2,500pg/ml within 3 days, the number of developing follicles can effectively and drastically reduced through target transvaginal aspiration, 1-3 PRIOR to planned the hCG trigger. This will almost invariably be accompanied by a rapid and significant drop in the plasma [E2] and in the process will drastically reduce reduce the risk of OHSS occurring without significantly compromising egg/embryo quality. The drawback of this effective approach is the fact that it interjects an additional surgical intervention into an already complex and stressful situation. i
  3.TRIGGERING WITH LOW DOISAGE hCG; Because of the fact that hCG augments the development of OHSS (unless preceded by “coasting”), may RE’s prefer to use a lower dosage of hCG for the “trigger. This is either done by administering 5,000U (half the traditional dosage) or by administering, a 250mcg (rather than 500mcg) of DNA recombinant form of hCGr (Ovidrel/Ovitrel. Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the “trigger” dosage of hCG administered (from 10,000U to 5,000U or 250mcg of recombinant hCG-Ovidrel) in the hope that by doing so the risk of critical OHSS developing will be lowered. While this might indeed be true, it is my opinion, that such a reduced dosage is usually insufficient to optimize the efficiency of egg meiosis, e3specially when there are so many follicles present. While the use of a reduced “trigger” dosage of hCG does indeed reduce the risk and occurrence of OHSS-related life-endangering complications, the price to be paid is reduced egg quality/”competency”.
  4.“TRIGGERING” WITH A GnRH AGONIST (E.G. “LUPRON/BUSERELIN): More recently, an increasing number of RE’s prefer to trigger meiosis by way of an agonist (Lupron/Buserelin/Superfact () “trigger” rather than through the use of hCG. The idea is to mimic what happens in natural cycles to promote egg maturation (meiosis) and ovulation, namely to have the agonist cause a “surge” in the release of body’s own pituitary LH to trigger egg meiosis (maturation) .But the amount of LH released in by the pituitary gland is often insufficient to optimize meiotic egg maturation and thus, while this approach also lowers the risk of OHSS it again comes at the expense of egg quality/competency.
  
  I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.
  •The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
  •Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
  •IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
  •The Fundamental Requirements For Achieving Optimal IVF Success
  •Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
  •Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
  •Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
  •A personalized, stepwise approach to IVF
  •Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting.
  •“Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
  •The “Lupron Trigger” to Prevent Severe OHSS: What are the Pro’s and Con’s?
  •Email: Julied@sherivf.com
  •Phone: 702-533-2691
  ?800-780-7437
  
  Geoff Sher
  
  I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Lina on April 6, 2017 at 4:57 pm

Dear Dr Sher , I had three failed ivf/icsi cycles due to unexplained infertility. Just to mention, two out of three cycles I did with the best clinic in London, UK. They use rigorous protocols with 1-2 blood tests and scans a day. Tests included immunes, nk cells (full immune,Chicago test), hysteroscopy, karyotyping, sperm fragmentation etc. My AMH is 26, FHS 3.6 and seem to react well to drugs; each cycle I had 16-18 eggs, 10 strong embryos and 2-3 blastocysts, good lining. It seems most of my embryos don’t survive after day 3 and 4. On my first cycle I got BFP but then miscarried due to Trisomy 9. What could I do differently if decide to have another go? Somehow I feel we overlooked something basic. Many thanks
Leena on April 6, 2017 at 2:01 pm

Dr Sher,

My embryology lab apparently mixes up all the day 5 embryos in one batch so they don’t know which one they will thaw (I have a BA and BB) because they feel thy all have an equal chance once they get to day 5. I find this disconcerting, is this normal in your experience?
- Dr. Geoffrey Sher on April 6, 2017 at 7:15 pm
  
  I personally usually prefer to know which eggs and embryos propagated said blastocysts. This helps select the best one’s for transfer in my opinion.
  
  Geoff Sher

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