Ask Our Doctors – Archive
Our Medical Directors are outstanding physicians that you will find to be very personable and compassionate, who take care to ensure that you have the most cutting-edge fertility treatments at your disposal. This is your outlet to ask your questions to the doctors.
Hi Dr Sher, how do you decide between a fresh and frozen ET? I only had 150iu GonalF from day5 (with Cetrotide) and my cycles are generally irregular. Would you have a preference for fresh vs frozen transfer in this instance?
Many thanks in advance!
Not on that basis alone!
Geoff Sher
Hello Dr. Sher – Last week I completed my first IVF cycle. I had 5 follicles larger than 20mm but no eggs at retrieval. During the IVF protocol, I used Lupron and Follistim. I also have hypothyroidism. As soon as I started the Lupron injections, my TSH skyrocketed to 18. My GP adjusted my dose twice just to get me back down to 6. My RE insisted that the Lupron would not effect my TSH, but my GP thought that this is exactly what was happening. Also, I read blogs from the UK where ladies stated that Lupron in the UK has the label warning “may cause thyroid enlargement”. Could you give me your opinion on the relationship between Lupron and TSH, and the effect this could have had on me not having eggs at retrieval? Thank you for any insight you can give!
Studies have not detected a statistically significant difference between baseline or TRH-stimulated serum TSH between control and GnRH-a (e.g. Lupron) -treated groups of women. Furthermore, these groups were similar with respect to routine thyroid function assays.
Geoff Sher
Hi Dr Sher,
My baseline e2 was less than 12 pg/mL. I am stim day 6 today (had my 6th stims this morning). I went in for my first e2 test this morning and it was 890 pg/mL. Is this too high for only 5 full days of stims? I have my first sonar tomorrow afternoon but will like to know what I am dealing with so long?
Not necessarily. I would stay the course!
Geoff Sher
In response to the reply to my question, how do I convince my doctor to do a fresh transfer despite an elevated progesterone? Are there any studies out there that I can access? Also, the fact they retrieved 6 eggs from 13 follicles could that mean I started ovulating before the extraction of the eggs? And the the fact that there was a rise in progesterone prior to ovulation, is that a sign of premature ovulation? Is this a sign of poor monitoring? I’m trying to figure out if I had a poor response to the medication or if I have poor quality of eggs with a low reserve since they only extracted 6 eggs and only 2 fertilized. What would be a reason so many eggs died during fertilization. Thanks.
The premature rise in progesterone suggests premature luteinization. Premature luteinization (“premature LH surge”) occurs when prior to the planned initiation of the hCG trigger, a progressive rise in LH, irreversibly compromises follicle and egg development and maturation. It is not a sporadic isolated event. It comes as a culmination of a series ovarian events, occurring mostly in susceptible women (i.e. usually older women and those with diminished ovarian reserve. It is more likely to occur when the protocol used for ovarian stimulation has failed to maintain LH activity at a low level prior to and throughout the ovarian stimulation process. Once it occurs in any given stimulation cycle it cannot be switched off by changing the stimulation in progress or by administering GnRH antagonists (e.g. Ganirelix/Cetrotide/Orgalutron) midway in the cycle in the hope that this could rescue the eggs under development. It is my opinion, once premature luteinization commences, the cycle is doomed and outcome is doomed to fail. The condition increases the likelihood of premature ovulation, failed release of eggs during needle-guided egg retrieval (so called “empty follicle syndrome” and the incidence of egg/embryo “incompetence” (chromosomal aneuploidy).
This situation is most commonly seen in older women and in women who have severely diminished ovarian reserve. In many cases its effect can be prevented through implementation of strategic and individualized protocols for controlled ovarian stimulation (COS) coupled with optimizing the type, timing and dosage of the “hCG trigger shot.”
Normally, following optimal ovarian stimulation, the “trigger shot” is given for the purpose of it initiating meiosis (reproductive division) that is intended to halve the number of chromosomes from 46 to 23 within 32-36 hours. The hCG trigger also enables the egg to signal the “cumulus cells” that bind it firmly to the inner wall of the follicle (through enzymatic activity), to loosen or disperse, so that the egg can detach and readily be captured at egg retrieval (ER).
Older women, and women with diminished ovarian reserve, tend to have more biologically active LH in circulation. LH causes production of male hormone (androgens, predominantly testosterone), by ovarian connective tissue (stroma/theca). A little testosterone is needed for optimal follicle development and for FSH-induced ovogenesis (egg development). Too much LH activity compromises the latter, and eggs so affected are far more likely to be aneuploid following meiosis.
Women with the above mentioned conditions often have increased LH activity and are thus more likely to produce excessive ovarian testosterone. It follows that sustained, premature elevations in LH or premature luteinization (often referred to as a “premature LH surge”) will prejudice egg development. Such compromised eggs are much more likely to end up being complex aneuploid following the administration of the hCG trigger, leading to fruitless attempts at retrieval and the so called “empty follicle syndrome.”
The developing eggs of women who have increased LH activity (older women, and women with diminished ovarian reserve) are inordinately vulnerable to the effects of protracted exposure to LH-induced ovarian testosterone. Because of this, the administration of medications that provoke further pituitary LH release (e.g., clomiphene and Letrozole), drugs that contain LH or hCG (e.g., Menopur), or protocols of ovarian stimulation that provoke increased exposure to the woman’s own pituitary LH (e.g., “flare-agonist protocols”) and the use of “late pituitary blockade” (antagonist) protocols can be prejudicial.
The importance of individualizing COS protocol selection, precision with regard to the dosage and type of hCG trigger used, and the timing of its administration in such cases cannot be overstated. The ideal dosage of urinary-derived hCG (hCG-u) such as Novarel, Pregnyl and Profasi is 10,000U. When recombinant DNA-derived hCG (hCG-r) such as Ovidrel is used, the optimal dosage is 500mcg. A lower dosage of hCG or Ovidrel can, by compromising meiosis, increase the risk of egg aneuploidy, and thus of IVF outcome.
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.
•Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
•The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
•Implications of “Empty Follicle Syndrome and “Premature Luteinization”
ANNOUNCEMENTS:
1.About my Retirement by mid-2018:
After > 30 years in the field of Assisted Reproduction (AR), the time is approaching for my retirement. If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
If you are interested in my medical services prior to my retirement, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com. You can also apply online at http://www.SherIVF.com.
2.The 4th edition of my newest book ,
“In Vitro Fertilization, the ART of Making Babies” is now available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.
Geoffrey Sher MD
Dear Sir,
I am six weeks pregnant and the first USG scan has confirmed multiple viable pregnancies with tri-amniotic and tri-chorionic embryos. I am just 5′ 2″ tall. I would like to know, does the factor of maternal height play any role while assessing the risks in triplet pregnancy?
Also, what factors should I take into consideration while deciding whether to go ahead with ‘expectant management approach’ or with ‘multifetal reduction approach’? I am getting very anxious about the current situation. Please help!
Thanks,
–Saana
I strongly advise against anything more than a twin pregnancy. That is why I rarely (if ever) agree to transfer >2 embryos. High order multiple pregnencies (triplets or greater), are associated with significant risks. Conversely, aside from the obvious emotional avulsion associated with pregnancy reduction, the risk of losing the entire pregnancy following selective pregnancy reduction is rather small. So, in my opinion, unless (following counseling) you are deemed not to be able to deal with the process, I would suggest reducing down to two (twins).
A healthy family is the dream of many young couples and most take it for granted that they will be able to conceive easily whenever they desire. In fact, in Western society there is much more concern about preventing an unwanted gestation than about the ability to conceive. In the general population, only about 20% of healthy young couples will conceive in any given month of trying. After three months approximately 50% of couples will have conceived and after 12 months, almost 85% will have achieved their goal. For this reason, infertility is defined as the failure to conceive despite one year of regular unprotected intercourse. Approximately 10-15% of couples will experience a fertility problem during their reproductive lifetime. The incidence of infertility seems to have increased over the past several decades and has been attributed to several factors including delayed childbearing, an increased prevalence of tubal disease and decreased social stigma associated with the condition.
Modern fertility treatment came of age in the early 1960’s with the advent of drugs to induce ovulation, including Clomiphene Citrate and human postmenopausal gonadotropins (hMG). These drugs can be use alone or in combination to improve follicular development. Many patients taking these medications will develop multiple ovarian follicles, which may increase the chance of conception per cycle. However, the trade off for improving pregnancy rates has been a dramatic increase in the number of multiple gestations.
The treatment of infertility was further advanced by the development in 1978 of In Vitro Fertilization (IVF), the most renown of the Assisted Reproductive Technologies (ART). Controlled Ovarian stimulation (COS) is somewhat less invasive and significantly less expensive than IVF. However, it is difficult to predict the response to medication in many patients and the success rate is less than half of what could be expected from one ART cycle.
Because of its complexity and labor intensiveness, ART is extremely expensive. The average cost on one IVF treatment in the United States is in the range of $12,000. However, the live birth rate per embryo transfer procedure remains only in the range of 30%-40%. The high cost and relatively low success rates from ART, combined with the fact that fertility treatment is not a covered benefit by most insurance companies in the United States, adds an enormous emotional and financial burden onto couples already struggling with an inability to conceive. This in turn, places pressure on clinicians to succeed at any cost.
Since 1998, advances in the field, including extended embryo culture capability and a renewed recognition of the importance of the embryo transfer procedure, have succeeded in improving ART success rates. Unfortunately, treatment success has been achieved at a considerable cost in terms of a dramatic increase in the number of multiple gestations. From 1980-1997, the number of annual live babies born from twin gestations rose 52%, from 68,399 to 104,137. In the same period the incidence of high-order multiple gestations rose 404%, from 1377 to 6737 (ASRM, 2000a, National Center for Health Statistics, 2000).
Not only is high-order multiple gestation the most common complication of infertility treatment, it has also become the most costly in terms of its social impact. Preterm delivery accounts for the bulk of perinatal morbidity and mortality If all of the factors associated with high-order multiple gestations are considered, including the costs of antenatal maternal hospitalization, neonatal intensive care for premature infants, as well as the costs of chronic medical care, rehabilitation and special education, the projected annual cost of ART-associated multiple gestations in the United States would be about $640 million compared to $550 million for all IVF cycles performed
The real and unappreciated challenge of reducing multiple pregnancies is complicated by a common belief among many infertility patients that multiple gestations are actually a favorable outcome. Most infertile patients are unaware of the potential complications associated with multiple gestations. Indeed, it is not uncommon for these patients, in the face of the high emotional and financial stakes involved with treatment, to express an interest in maximizing the use of their resources by completing their family in one attempt. In fact, most patients do not even perceive any great risk associated with twin gestations and the vast majority of IVF patients openly express a desire to conceive twins. More alarming is the fact that based on the perceived urgency for conception among women in their later reproductive years, some couples are even interested in conceiving triplets or beyond,. Education is clearly needed because if patients truly understand inherent risks, they may be less likely to request overly aggressive treatment.
It is neither rational nor ethical for physicians to fail to accept their share of responsibility for the high rate of multiple gestations from ART. Because of the relatively low success rate per cycle, clinicians are forced to continually weigh the risk of multiple gestations to the even greater risk of not conceiving at all. In patients over 40 years of age, as well as in those with multiple previous treatment failures, it is not uncommon for physicians to transfer more embryos than would normally be considered reasonable .Unfortunately, competition between IVF clinics to produce high success rates may also unduly influence some physicians to treat more aggressively than is warranted.
Experience in treating fertility disorders heavily influences optimal outcome, especially among high-risk patients. For example, patients with a diagnosis of polycystic ovarian syndrome (PCOS) tend to produce multiple follicles, even on very low doses of stimulation and accordingly are at a particularly high risk for multiple gestations. These patients are often highly sensitive to the medication and. The injudicious use of injectible gonadotropins in such patients can have disastrous consequences, as exemplified by the octuplets born several few years ago. In an injectible gonadotropin/ intrauterine insemination cycle, once ovulation is triggered, no mechanism exists to control the number of eggs ovulated, the number fertilized or the number of embryos that implant, unless one cancels the cycle or advises the patient not to have intercourse. Even when such prescriptions are given, patients occasionally find cogent reasons (in their minds) to avoid them. In my opinion, many patients with PCOS could be better be served by foregoing a trial of ovulation induction and proceeding directly to IVF, in which the risk of high-order multiple pregnancy can be minimized by limiting the number of embryos transferred. Because many generalist Obstetrician/ Gynecologists presently feel comfortable treating infertility patients with injectible gonadotropins, it is essential that these practitioners recognize when it is time to involve a specialist.
Several strategies have been proposed in an attempt to reduce the number of triplet pregnancies resulting from Ovulation Induction. The first of these were introduced in the mid-1970s in response to the observation that the multiple gestation rate was on the rise secondarily to the recently popularized ovulatory medicines, clomiphene and hMG. . Because of wide variation in the individual response to ovarian stimulation, many clinicians recommend monitoring follicular development with serial ultrasound and estradiol levels. This practice is based upon the idea that, because these measurements correlate with ovarian responsiveness to stimulation, arbitrary values can be used as ‘threshold values’, above which risk of multiple gestations is deemed unacceptably high.
Central to reducing the risk of high order multiple pregnancies is limiting the number of embryos transferred. Selecting appropriate embryos for transfer has always been a major challenge of IVF. Today using blastocyst (advanced, day 5-6 embryos) transfers where the implantation rate is much higher than when earlier (cleaved), day 2-3 embryos are transferred.. Thus, in my opuion no justification for transferring >2 embryos at a time.
Despite efforts to reduce multiple pregnancies by selecting the best embryos for transfer and by limiting the number of embryos transferred to no more than two (2) for most patients, the problem of ART-associated multiple gestation relates to another important issue as well and that is the increased incidence in ART pregnancies of monozygotic twinning that results from embryos splitting in two.
As a last resort, multifetal pregnancy reduction is a method for reducing the incidence of preterm labor and delivery associated with high-order multiple gestations The potential need for this procedure places couples with an ART-induced multiple gestation in the difficult position of choosing between terminating a pregnancy they worked hard to achieve and continuing with the pregnancy despite a significant potential for premature labor and delivery. While acknowledging the inadequacy of this option, at present it may be the less objectionable of two unpalatable choices.
The best way to reduce the incidence of multiple gestations is to transfer only one (1) embryo at a time…i.e. Single Embryo Transfer (SET). The premise of SET is to select the single best quality embryo for transfer. While this is a noble goal, attempts at SET to date have resulted in disappointingly low overall pregnancy rates, making the concept difficult to implement in a country such as the United States where infertility treatment is almost always an out-of-pocket expense.
In summary, the high rate of multiple gestations resulting from ovulation induction and ART is a complex problem that can no longer be justified as an acceptable side effect of treatment. The Hippocratic Oath states the cardinal rule of medicine as “primum non nocere; foremost do no harm.” It is imperative that this issue be addressed at multiple levels. This includes increasing insurance coverage for fertility treatment, educating patients to the risks of high-order multiple gestations, as well as the steps practitioners can take to mitigate those risks, such as tailoring the treatment to the specific needs of each patient and limiting the number of embryos transferred. Assisted Reproductive Technology is one of the successes of modern medicine. It would be unfortunate if this success were to be overshadowed by the creation of an even worse problem. The challenge is ours.
Good luck and G-d bless!
Geoff Sher