“Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist

Ideal egg development sets the scene for optimal egg maturation that occurs 36-42h prior to ovulation or egg retrieval. Without prior optimal egg development (ovogenesis), egg maturation will be dysfunctional and most eggs will be rendered “incompetent” and unable upon fertilization to propagate viable embryos. In IVF, optimal ovogenesis requires the selection and implementation of an individualized approach to controlled ovaria stimulation (COS). Thereupon, at the ideal time, maturational division of the egg’s chromosomes (i.e. meiosis) is “triggered” through the administration of hCG or an agonist such as Lupron, which induces an LH surge. The dosage and timing of the “trigger shot” profoundly affects the efficiency of meiosis, the potential to yield “competent” (euploid) mature (M2) eggs, and as such represents a rate-limiting step in the IVF process.

Triggering meiosis with Urine-derived hCG (Pregnyl/Profasi/Novarel) versus recombinant hCG (Ovidrel): Until quite recently, the standard method used to “trigger” egg maturation was through the administration of 10,000 units of hCGu. Subsequently, a DNA recombinant form of hCGr (Ovidrel) was introduced and marketed in 250 mcg doses. But clinical experience strongly suggests that 250 mcg of Ovidrel is most likely not equivalent in biological potency to 10,000 units of hCG.  It probably only has 50%-70% of the potency of a 10,000U dose of hCGu and as such might not be sufficient to fully promote meiosis, especially in cases where the woman has numerous follicles. For this reason, I firmly believe that when hCGr  is selected as the “trigger shot” the dosage should best  be doubled to 500 mcg at which dosage it will probably have an equivalent effect on promoting meiosis as would 10,000 units of hCGu. Having said this, it is my personal opinion that it is unnecessary to supplant hCGu with hCGr since the latter is considerably more expensive and is probably no more biopotent than the latter.  

Some clinicians, when faced with a risk of OHSS developing will deliberately elect to reduce the dosage of hCG administered as a trigger in the hope that by doing so the risk of critical OHSS developing will be lowered. It is my opinion, that such an approach is not optimal because a low dose of hCG (e.g., 5000 units, hCGu or 25omcg hCGr) is likely inadequate to optimize the efficiency of meiosis  particularly when it comes to cases such as this where there are  numerous follicles.  

It has been suggested that the preferential use of an “agonist (Lupron) trigger” in women at risk of developing severe ovarian hyperstimulation syndrome could potentially reduce the risk of the condition becoming critical and thereby placing the woman at risk of developing life-endangering complications. It is with this in mind that many RE’s prefer to trigger meiosis by way of an “agonist (Lupron) trigger rather than through the use of hCG.  The agonist promptly causes the woman’s pituitary gland to expunge a large amount of LH over a short period of time and it is this LH “surge” that triggers meiosis. The problem with using this approach, in my opinion, is that it is hard to predict how much LH will be released in by the pituitary gland.  For this reason, I personally prefer to use hCGu for the trigger, even in cases of ovarian hyper stimulation with one important proviso – she underwent “prolonged coasting” in order to reduce the risk of critical OHSS, prior to the 10,000 unit hCGu “ trigger”.

The timing of the “trigger shot” to initiate meiosis:  This should coincide with the majority of ovarian follicles being >15 mm in mean diameter with several follicles having reached 18-22 mm. Follicles of larger than 22 mm will usually harbor overdeveloped eggs which in turn will usually fail to produce good quality eggs. Conversely, follicles less than 15 mm will usually harbor underdeveloped eggs that are more likely to be aneuploid and incompetent following the “trigger”.  

 

4 Comments

Abbey

I’ve done 3 rounds of IVF and have had difficulty retrieving eggs in all 3 cycles. I’m 36 years old with a 3.9 AMH level. My protocol was 150u of Menopur, 150u or 175u of Gonal F (went up to 175u in the 3rd cycle) and 5u of Lupron while on stims. I start with 10u of Lupron when I start the birth control pill and decrease it to 5u when stims are introduced. For cycles 1 and 3, my trigger has been Ovidrel and for cycle 2, my trigger was Pregnyl. First cycle yielded 2 eggs (expecting 8), second cycle yielded 11 eggs (expecting 13-15) and third cycle yielded 4 eggs (expecting 15-17). Each time, we get far fewer eggs than we’re expecting. Estradiol levels have been good too – 3400 in cycle 2, 3641 in cycle 3. Basically, everything looks great on paper and then we have such poor results during retrievals. Do you have any thoughts on what is causing the retrieval problems? Do you think it has to do with the drug protocol or trigger shot? I’ve been on stims for 9 days in each cycle.

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Dr. Geoffrey Sher

Hi Abbey,

In my opinion, your protocol for ovarian stimulation needs to be reviewed and revised. This is likely where the problem lies. It is my opinion that you might be getting too low a dosage of Ovidrel or Pregnyl.

Here is the protocol I advise for women, who have adequate ovarian reserve.
My advice is to use a long pituitary down regulation protocol starting on a BCP, and overlapping it with Lupron 10U daily for three (3) days and then stopping the BCP but continuing on Lupron 10u daily (in my opinion 20U daily is too much) and await a period (which should ensue within 5-7 days of stopping the BCP). At that point an US examination is done along with a baseline measurement of blood estradiol to exclude a functional ovarian cyst and simultaneously, the Lupron dosage is reduced to 5U daily to be continued until the hCG (10,000u) trigger. An FSH-dominant gonadotropin such as Follistim, Puregon or Gonal-f daily is started with the period for 2 days and then the gonadotropin dosage is reduced and a small amount of menotropin (Menopur—no more than 75U daily) is added. This is continued until US and blood estradiol levels indicate that the hCG trigger be given, whereupon an ER is done 36h later. I personally would advise against using Lupron in “flare protocol” arrangement (where the Lupron commences with the onset of gonadotropin administration.
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
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF
• “Triggering” Egg Maturation in IVF: Comparing urine-derived hCG, Recombinant DNA-hCG and GnRH-agonist:
If you are interested in my advice or medical services, I urge you to contact my patient concierge, ASAP to set up a Skype or an in-person consultation with me. You can also set this up by emailing concierge@sherivf.com or by calling 702-533-2691 and/or 800-780-743. You can also enroll for a consultation with me, online at http://www.SherIVF.com.
Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com .

Geoffrey Sher MD

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Adelle stevenson

I am on my 4th cycle and have always had 250mg of ovidril as my trigger. I am 41yrs old with Amh of 10 ( which I’m sure has reduced after 2 failed cycles in a row) I have only had 3 mature eggs from my last 2 cycles. ( 1st cycle elenova/menopur 250mg & 2nd cycle gonal f 275mg/luverus)
This cycle I am on decapeptyl & 450 menopur with 250mg ovidril trigger. Would you suggest I ask my for a double trigger? I am doing ivf in Australia

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Dr. Geoffrey Sher

In my opinion, 250mcg Ovidrel is not an optimal trigger dosage. I believe it should be doubled.

Geoff Sher

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