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.
Dr Sher,
I naturally ovulate cycle day 17. I am doing FET this cycle and we are testing progesterone and doing US on cycle day 14 and doing transfer on cycle day 20. I’m afraid i could ovulate after they test progesterone, in esp worried since I’m only on oral Estrace 2mg twice a day. Should I do ovulation strips or ask them to text progesterone again sooner? Thank you.
There are different ways to prepare the uterus for FET. Some authorities favor the use of commercially available oral estradiol products (e.g. Estrace, Progynova), while others recommend transdermal, transvaginal, or subcutaneous/intramuscular estradiol injections. The problem with oral estradiol administration is firstly that anything taken orally will upon gastrointestinal absorption, first pass through the liver (via the venous portal system) before being delivered into the systemic circulation and to the uterus. It is processed in the liver so what reaches the uterus is an altered substance and is substantially watered down. Secondly, the most commonly used form of estradiol, namely Estrace, readily metabolizes into both estradiol and estrone which could be prejudicial to optimal endometrial development. Trans-vaginal (suppositories) and trans-dermal (skin patches) administration also have drawn-backs that relate to erratic and unpredictable absorption issues. In my opinion, the optimal way to administer estrogen for endometrial development in preparation for embryo reception (FET), egg donor-IVF and gestational surrogacy) is through the twice weekly intramuscular administration of (slow release) estradiol (e.g. Delestrogen). This method of estradiol delivery allows for even absorption and is delivered directly to the uterus via the systemic circulation without having first to pass through the liver. I have advocated the use of
Delestrogen for uterine preparation exclusively for more than 20 years. Results are excellent and I see s no reason to change. Here is how I implement the treatment:
It starts with administering an oral contraceptive (OC) to the recipient. This is later overlapped with Lupron daily for 5-6 days. The oral contraceptive is then withdrawn, but the daily Lupron injections are continued until the onset of menstruation at which point the Lupron dosage is reduced and intramuscular (IM) estradiol valerate (Delestrogen) is administered every 3 days. The objective of the estradiol is to achieve and sustain an optimal plasma E2 concentration of 500pg/ml-1,000pg/ml and a 9mm endometrial lining as assessed by ultrasound examination. Intramuscular and/or intravaginal progesterone is administered daily starting about 6 days prior to the FET and continued along with twice weekly IM Delestrogen until the 10th week of pregnancy or until it has been confirmed that the patient is not pregnant.
Daily oral dexamethasone commences with the Lupron start and continues until a negative pregnancy test or until the completion of the 8th week of pregnancy. Then it is tapered down and discontinued. The recipient also receives prophylactic oral antibiotics starting with the initiation of Progesterone therapy, until the day after ET. Usually we would thaw vitrified blastocysts with the objective of having 1, 2 or 3 for transfer; depending on a couple’s stated preference. Commencing on the day following the ET, the patient inserts a vaginal progesterone suppository daily and this is continued until the completion of the 8th week of pregnancy or until a negative pregnancy test.
As an alternative regimen for women who cannot tolerate intramuscular Progesterone (PIO), we prescribe either Crinone vaginal gel or Endometrin vaginal inserts according to protocol. If you’d like to explore one of these options, talk to your physician. For blastocyst FET’s, the blood pregnancy tests are performed 13 days and 15 days after the first progesterone administration is commenced.
Geoff Sher
PH: 800-780-7437
Dear Dr. Sher
I am on Gonal IUI cycle. On the last CD12 scan, i had 2 follicles at 17.7mm and 17.6mm with a lining 11.5mm. I was supposed to trigger with Ovitrelle at 23.30 that evening following with IUI 36 hrs later. An hour after that last scan, i had almost positive OPK, which was negative 2 hrs later then positive again and negative again before a trigger at 23.30. I had all the ovulation symptoms but took a trigger anyway. I have couple of questions please:
1) can it be that my body was only gearing up for ovulation but have not had one? (symptoms eased off next day, just had a bit of cramping and a twinge in the uterus every now and then)
2) is there any point to proceed with IUI as planned 36 hrs post-trigger if the ovulation indeed happened so early?
3) if i had a spontaneous natural surge started that morning, can Ovitrelle taken at 23.30 “override” it with the ovulation still happening around 36hrs mark
4) can IUI still be successful 36hrs post -trigger considering all of this.
THANK YOU!
P.S. the clinic will not do another scan before IUI. Apparently, “this will not be beneficial as the egg lives 48hrs (?!) anyway. However, I’m concerned that with IUI 48 hrs after first positive OPK (and 36 hrs after trigger), i’ll miss fertile window as i understand that an egg only lives for 12-24 hrs max. Thanks a lot again!
Jane
1) can it be that my body was only gearing up for ovulation but have not had one? (symptoms eased off next day, just had a bit of cramping and a twinge in the uterus every now and then)
A: The urine ovulation test and its interpretation is very subjective and subject to variation. can vary. If in doubt a blood LH should be measured. This is how I advise my patients:
“Commencing at least 17 days before the expected menstrual period (i.e.; usually about 10 days following the initiation of menstruation), urine should be collected twice daily and tested for the onset of the spontaneous luteinizing hormone (LH) surge. The initiation of the LH surge usually precedes ovulation by 8 to 36 hours. In order to detect the onset of the LH surge accurately, an early morning urine specimen is needed. Ideally, the bladder should be emptied first thing in the morning, upon awakening. About one half-hour later urine is collected (only a very small amount is required) and tested using an over-the-counter LH – kit (obtainable over the counter, at a drug store). At the earliest sign of a color change the woman should plan on presenting at my office within 24 hours for IUI.
2) is there any point to proceed with IUI as planned 36 hrs post-trigger if the ovulation indeed happened so early?
A: Ovulation occurs about 38-42 hours after the trigger and IUI should be done prior to ovulation.
3) if i had a spontaneous natural surge started that morning, can Ovitrelle taken at 23.30 “override” it with the ovulation still happening around 36hrs mark
A: If the urine test is +ve prior to the trigger being contemplated, it is not a good sign because it points to premature luteinization.
4) can IUI still be successful 36hrs post -trigger considering all of this.
A: Frankly, I would not be very optimistic.
Intrauterine insemination (IUI), the injection of sperm into the uterus by means of a catheter directed through the cervix, has been practiced for many years. The premise of this procedure is that sperm can reach and fertilize the egg more easily if placed directly into the uterine cavity. IUI is a procedure that bypasses the cervix and places specially prepared sperm into a woman’s uterus around the time of natural or induced ovulation. The suggested advantage of IUI is that it shortens the path that sperm would normally take to a woman’s fallopian tubes.
In the early ‘60s, physicians were injecting small quantities of raw, untreated semen, (sperm plus the seminal plasma) directly into the uterus at the time of expected ovulation. However, when more than 0.2 ml of semen was injected in to the uterus, serious and sometimes life endangering shock-like reactions often occurred. It was subsequently identified that the reason for such reactions related to the presence of prostaglandins within the seminal plasma. This led to the practice of injecting small amounts (less than 0.2 ml) of raw semen. However, the pregnancy rates were dismal and side effects, such as severe cramping and infection were rampant.
Soon after establishing the Northern Nevada Fertility Center in Reno in 1982 (the Nation’s first private in vitro fertilization (IVF program), we began to recognize the potential advantage of washing and centrifuging raw semen, so as to separate sperm from the seminal fluid, and thereby remove prostaglandins that cause most of the problems. We subsequently introduced and, thereupon, became the first to publish on intrauterine insemination (IUI) in the Journal, Fertility and Sterility (April 1984).
Indications for Intrauterine Insemination (IUI)
•Artificial insemination using frozen (donor) sperm: The recognition of HIV infection as a sexually transmitted disease, coupled with the fact that the virus is present in semen months before it can be detected in the blood, mandates that all donors have their semen cryopreserved (frozen) and stored for at least six months, whereupon, they be re-tested for HIV infection. Only upon confirmation of a negative test should the cryopreserved semen specimen be thawed and used for insemination. Since cryopreservation inevitably reduces sperm motility and function, it is not adequate to simply thaw the frozen specimen and then inseminate the raw semen into the vagina. Rather, the semen specimen should be processed for IUI. Provided that the recipient is ovulating normally, there is no need to administer fertility drugs, such as Clomiphene, Pergonal, etc.
•Artificial insemination with partner’s sperm: In cases of sexual dysfunction (impotence, retrograde ejaculation, etc.) or timing issues, partner’s sperm may need to be collected and processed in preparation of IUI.
•Cervical mucus hostility: Sometimes the cervical mucus acts as a barrier to the activation and passage of sperm as it passes through the cervical canal. Such hostility may be due to poor physical qualities of the mucus, cervical infection, or the presence of antisperm antibodies. In all but the latter situations, IUI can readily be performed during natural cycles, unless the woman has ovulation dysfunction. However, when infertility results from the presence of antibodies in the cervical mucus, IUI will likely be ineffectual and should be replaced by in vitro fertilization (IV).
•Absent or dysfunctional ovulation: In some cases where the woman requires the use of fertility drugs to induce normal ovulation, the concomitant performance of IUI might improve pregnancy rates.
Selecting the Fertility Drugs for Intrauterine Insemination (IUI)
Clomiphene citrate (Serophene, Clomid): Clomiphene citrate is taken orally for 5 days starting on day 2 to 5 of the menstrual cycle. Ovulation will usually occur 10 days later. In some cases, hCG is used to trigger the ovulation but this is often unnecessary. Clomiphene is a relatively inexpensive and safe method for inducing ovulation and this is why it is so commonly prescribed to women undergoing IUI. However, women receiving clomiphene have about a one third lower pregnancy rate per cycle than is the case using injectible fertility drugs. but it there are draw-backs. Here are a few reasons why this is so:
1)Clomiphene citrate is an anti-estrogen. .Ordinarily normally ovulating women (without exposure to clomiphene) produce a single dominant follicle which produces enough estrogen to promote optimal cervical mucous production and an adequate endometrial lining (>9mm) However, with clomiphene is used to induce ovulation, its anti-estrogenic effect blunts this response. In fact on clomiphene,it requires much more estrogen to override this effect such that unless at least 3 large follicles develop so as to allow the blood estradiol levels to rise above 400pg/ml, cervical mucus production and endometrial development will usually be insufficient to allow a healthy pregnancy to occur. Younger women with normal ovarian reserve (Day-3 FSH of <9miu/ml) will usually produce >3 follicles where as women over 40 years of age and those (regardless of age) with diminished ovarian reserve will rarely do so and thus are very unlikely to achieve viable pregnancies on clomiphene
2)Clomiphene induction of ovulation is associated with a 15-20% chance of a condition called luteinized unruptured follicle (LUF) syndrome where the hormonal changes that precede and accompany and follow ovulation (including a rise in blood progesterone level) occur but this happens without ovulation occurring .LUF syndrome thus leads to the erroneous conclusion that an egg has been released when, in fact, it remains “trapped” in the ovarian follicle.
3)More than 3 consecutive (back to back) of clomiphene will result in a very significant increase in the anti-estrogen effects (referred to in 1&2 above), such that unless a break of at least 1 full menstrual cycle is taken, the likelihood of a viable pregnancy declines to less than 10%, regardless of the woman’s age or her ovarian reserve.
4)Increased production of Luteinizing Hormone: Clomiphene causes the pituitary gland to produce increased amounts of FSH and LH. FSH promotes follicle growth development while excess LH causes the ovary to produce male hormones such as testosterone. While a little testosterone is indispensable to follicle and egg development, too much testosterone can have the reverse effect and harm egg development. This effect is even more deleterious in women with diminished ovarian reserve (elevated FSH levels) and those over 40 whose ovaries tend to produce more testosterone-like hormones.
The following additional factors must be considered when it comes to the use of Clomiphene:
1)It is best not being prescribed for more than three consecutive months in a row to anyone and certainly not without taking a full cycle break before restarting a fourth cycle of treatment. The reason is that after the 3-4 consecutive months of clomiphene therapy, the anti-estrogenic properties are compounded to the effect of virtually converting it to an anti-fertility drug. This explains why >80% of successful clomiphene pregnancies occur within the first 3 months of treatment, and why the vast majority of clomiphene pregnancies that occur after >3 consecutive (back-to-back) cycles of treatment are lost (usually due to early miscarriages).
2)Clomiphene should not be used in women that have diminished ovarian reserve (e.g. women with elevated FSH levels) or in women over 40 years of age.
The good news is that upon discontinuation of Clomiphene for 4-6 weeks, adverse effects disappear, leaving the slate clean.
The real benefit of clomiphene lies in its oral route of administration, low incidence of side effects, and its low cost. The birth rate per clomiphene IUI is about 7-10% per cycle of treatment (about 1/3 lower than when injectible fertility drugs are used.
Letrozole(Femara): Letrozole, like clomiphene is an oral agent induces ovulation that causes the pituitary gland to release large amounts of FSH as well as LH. The advantage that Letrozole has over clomiphene is that unlike the latter, it is NOT anti-estrogenic and thus does not compromise development of the uterine lining or adversely affect the production of cervical mucus. However as is the case with clomiphene, Letrozole causes increased LH release that can lead to overproduction of male hormones (e.g. testosterone) by the ovaries with potentially adverse effect on egg/embryo quality.
Thus while Letrozole does have potential advantages over clomiphene, the exaggerated LH-induced testosterone effect, especially in women over 40 years of age and/or those with evidence of diminished ovarian reserve limits its value.
Gonadotropins (Menopur, Gonal-f, Folistim and Puregon:) Women with absent or abnormal ovulation who require fertility drugs in preparation for IUI should receive gonadotropins. Granted, these agents are more expensive than clomiphene, but they have no anti-estrogenic properties.
The birth rate with gonadotropin IUI in women under 35 years of age (in the absence of male infertility, where it is much lower) is about 10-15%. However, success is affected by, and contingent upon, the procedure being performed (1) for the correct indications, (2) avoiding the performance of IUI when contraindications exist (see below) and, (3) where the woman is ovulating normally on her own. Success rates decrease as a woman’s age advances. In women 35-40 years of age the birth rate is 5-10% per cycle and for over 40 years, the birth rate per cycle is under 2%, declining to less than 1% after age 43.
Relative Contraindications to Intrauterine Insemination (IUI)
Advancing age: A woman’s natural ability to conceive declines with age starting after age 30. It falls more rapidly after age 35 and then, precipitously so after 40. The main reason for this is that the percentage of eggs that become chromosomally abnormal (aneuploid) through “wear and tear” increases as she gets older, such that by age 40 an ovulated egg is probably 3 times less likely to be able to propagate a viable pregnancy than at age 30. This explains the fact that under 35, the normally ovulating woman who receives injectible fertility drugs to induce ovulation has about a 10-12% chance of having a baby. In comparison, after age 40, the same woman would have about a 2% chance. For this reason alone, IUI is best suited to women under 35 and, in my opinion, should NOT be undertaken after age 40. Ages between 35 and 40 represent a “gray area.”
Significant Male Infertility: Contrary to popular belief, the performance of IUI in cases of male infertility does not improve success rates over regular and well-timed intercourse alone. In vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) is the only method to optimize pregnancy rates in association with male refractory infertility.
Tubal damage
1.Post-Pelvic Inflammatory Disease (PID): It is very important to understand that Fallopian tubes are not mere “pipes” through which sperm, egg and embryo must pass to achieve an intrauterine pregnancy. They are vital and sophisticated organs that serve intricate functions in the reproductive process. They transport sperm in the direction of the ovary, while at the same time, the fimbriae (petal-like extrusions at the end of the tube) apply themselves to the area of the ovary from which the egg is ovulating in order to pick up the extruding egg, and carry it back down the tube towards the uterus. About one third of the way back, the egg encounters the sperm and fertilization occurs. Thereupon, the resulting embryo is transported to the uterine cavity where it hopefully will implant.
PID, the commonest cause of damaged Fallopian tubes will, unless it is diagnosed and effectively treated very early on, inevitably and permanently disrupt the sophisticated function and continuity of the inner lining of both Fallopian tubes. In more severe cases, the intricate muscular arrangement of the tubal wall is also damaged, compromising the time-sensitive and programmed migration of sperm, egg and embryo. In advanced cases of PID, the fimbria fuse, thus compromising egg pick-up, and ultimately blocking the tube(s) completely.
PID almost always affects both Fallopian tubes. Indeed, one tube might be more damaged than the other, but both will be affected to a greater or lesser degree. That is why, even if one tube remains or is surgically rendered patent, the problem of markedly reduced fertility and the increased risk of a subsequent tubal pregnancy remains an ever present risk and reality. Thus, the use of fertility drugs to induce ovulation, or the use of microsurgery to open Fallopian tubes and free surrounding adhesions are often not curative of infertility. Furthermore, in cases where a pregnancy follows, the result is often a tubal (ectopic) gestation. This also serves to explain the fact that the intrauterine pregnancy rate following ovulation induction (with or without concomitant IUI) is likely to be to be at least 10 times lower in women with PID, and why, when a pregnancy does ensue, it is 10 times more likely to be a tubal (ectopic).
Thus, in women who have had PID, IVF is the only way to safely bypass the “damaged plumbing” and initiate a viable intrauterine pregnancy.
2.Post-Tubal Ligation. In large part, the same holds true following successful reconnection of previously ligated (tied) Fallopian tubes. The reason is that even with successful surgical reestablishment of tubal patency, there is always a degree of shortening of the tube(s) or a degree of damage due to surgical scarring of the inner lining of the tube(s). Even when tubes are normal, the birth rate per IUI cycle is about 10%, and following any form of tubal damage (PID or surgically-induced) the success is 5-10 times lower per IUI cycle (i.e. 1%-2%). Hence, IUI can hardly be justified in such cases, and IVF becomes the only effective and viable option.
Endometriosis:
While the exact cause of endometriosis remains an enigma, it is now apparent that immunologic dysfunction is a significant feature of this disease, and that a toxic environment exists in the pelvis (surrounding the tubes and ovaries) in patients with this condition. As a consequence, ovulation – whether spontaneous or induced by fertility drugs – commits the egg to pass through a toxic pelvic environment in order to reach the sperm waiting in the fallopian tube. This significantly reduces the egg’s fertilization potential. Furthermore, once the fertilized egg reaches the uterus, immunologic factors associated with endometriosis increase the risk of the embryo being rejected before pregnancy can be diagnosed. Such women may experience repeated “mini-miscarriages.”
In spite of these anti-fertility influences, many women with mild endometriosis do in fact conceive on their own, or following ovarian stimulation with fertility drugs. However, for reasons already referred to, the chances of conception are significantly reduced. And if they are ovulating normally on their own, the addition of fertility drugs will afford no additional benefit. Simply put, women in their late 20’s to early 30’s who have the time can anticipate about a 40% chance of conceiving on their own within two or three years (contingent upon their ovulating normally and having a fertile male partner). The occurrence of pregnancy in the latter cases occurs in spite of, rather than due to, such treatment. Such women may consider deferring any invasive treatments in favor of a “wait-and-see” approach. Conversely, women over the age of 35 whose egg quality is inevitably on the decline, IVF offers the only rational approach.
Fertility Drugs and Multiple Births
Normally ovulating women usually develop a number of follicles (fluid filled spaces within the ovary (ies) that contain eggs and produce estrogen) during the first week of the menstrual cycle. All but one (and sometimes two) of the follicles fail to develop to the point of being eligible for ovulation. The process is known as Selection. It is important to recognize that in all normally ovulating women, the one or two follicles selected to ovulate will inevitably be larger than the remaining follicles, regardless of whether the woman is receiving fertility agents such as Clomiphene or Pergonal, etc. Simply put, one or two follicles will always show enhanced development over the others, and as soon as these selected follicles ovulate, all the remaining follicles are rendered incapable of following suit. As a result, normally ovulating women no not have a greater incidence of high order multiple pregnancies. In contrast, women who do not ovulate at all, and those who ovulate irregularly or dysfunctional do not have the ability to select one or two dominant follicles for ovulation. As such, following the administration of fertility drugs for ovarian stimulation, numerous follicles may develop at the same rate, and several eggs can be ovulated simultaneously. This translates into a greater chance of pregnancy, but also a greater chance of multiple pregnancies. It is interesting that almost all reported cases of high order multiple pregnancies (greater than twins) following the use of fertility drugs have occurred in women who do not ovulate normally on their own.
It follows that only those women with absent or abnormal ovulation are at-risk for high order multiple pregnancies. They, therefore, need to be counseled regarding the consequences of premature birth and the availability of selective pregnancy reduction towards the end of the third month of pregnancy. Another alternative is to avoid the issue completely by choosing in vitro fertilization (IVF), where the number of potential babies can be limited by the number of embryos transferred to the uterus.
It is indeed unfortunate that fertility treatment has become so regimented that most patients find themselves being ushered through a scripted treatment process. As an example, clomiphene, though favored for its convenience and low cost, does NOT yield the same success as IUI with gonadotropin stimulation. In fact the per-cycle success rate of IUI using clomiphene is about 30% less. Also, women with endometriosis (regardless of severity) have much lower success with IUI (see above). Women over age 40 have such a low success with IUI that they cannot afford the time wasted in the process. Such women need IVF.
For the majority of couples who require an individualized strategic plan of action at an early stage, such an approach is emotionally, physically, and financially draining, leaving them both suspicious and critical of the intent of the medical profession.
The introduction of inexpensive Micro-IVF changes the landscape. In fact, the success rate is three times higher than with IUI. This plus the low the relatively low cost of Micro-IVF (as compared with conventional IVF) is a major advantage of the approach.
Good luck!
Geoff Sher
Dear Dr Sher,
This is the first time I have written anything online about my fertility treatment experience. Last summer, at the age of 37, I commenced a 3-cycle package of egg freezing. I had just started an amazing relationship and wanted to give that relationship the space to grow, without the loud clicking of a biological clock. The first cycle, in June, did not go so well. I have DOR (0.7 AMH with 11 AFC). As part of an egg freezing package, I was given a short protocol with a lot of meds (started at 375 menopur, but increased to 450 at 5 days in) and then Lupron trigger. Some of the follicles were ’empty’, 5 eggs were retrieved and only 3 were mature. Thanks to reading your arguments on the importance of an hCG trigger for older patients with DOR and no danger of OHSS, I insisted on changing the trigger. In September 2016, with 150 Gonal F and 300 menopur from the start, and a hCGr trigger, 6 eggs mature eggs were retrieved and frozen. For starters, I want to profoundly thank you for the advice you have publicly offered on the importance of the correct trigger, and all the advice you offer people pursuing IVF generally. Many of us are stuck between (1) trawling through huge amounts of individual experiences on TTC forums and (2) the extreme marketisation of these treatment at big clinics. I have now begun my final round of ‘freezing’ at the age of 38. Again, this is part of a 3-cycle package, within a big clinic that doesn’t unfortunately make much effort to individualise treatment or pursue the longer protocols that you recommend. My AFC was 12 at the first scan, before stimulation. And, since September, I have been taking Vitamin D, prenatal vitamins and regular acupuncture. For this third cycle, my partner (whom I just met last spring) and I wish to freeze embryos, in the hope that some eggs will fertilise. Honestly, because I feel that my current clinic is keen to up-sell me on all treatments, I wondered if I could ask you some advice. The second question below may simply require the expertise of the embryologist on the day. But I particularly keen to hear your thoughts on the value of ICSI for older women.
1. My partner is having his semen tested today. There is no reason at this stage to assume that it isn’t healthy. We can, however, elect to have ICSI. This costs an extra $1600 (the last of my savings). Seeing that I am likely to produce only a small batch of mature eggs and many may be chromosomally compromised, is there value in pursuing ICSI, regardless of the sperm analysis?
2. Would you recommend a blastocyst freeze, at all costs? Or is there any potential in a relatively weak 3-day embryo being put on ice?
Again, I’m very grateful for all the public advice you offer and for helping me to double the number of mature eggs frozen in my last cycle.
Thank you,
Camilla
I regret the ordeal you are having to go through. It is a pity!
YOUR QUESTIONS:
1. My partner is having his semen tested today. There is no reason at this stage to assume that it isn’t healthy. We can, however, elect to have ICSI. This costs an extra $1600 (the last of my savings). Seeing that I am likely to produce only a small batch of mature eggs and many may be chromosomally compromised, is there value in pursuing ICSI, regardless of the sperm analysis?
Intracytoplasmic Sperm Injection ICSI which began in 1992 as a treatment for severe male factor infertility, involves the direct injection of a single sperm into each egg under direct microscopic vision.
Soon after the turn of the 20th century it was reported that while the diagnosis of a male factor infertility had remained static, the use of ICSI had markedly increased and that indications for ICSI had expanded from solely male infertility (for which it had primarily been developed) to a wide variety of other indications such as “unexplained infertility, unexplained IVF failure, polycystic Ovarian Syndrome (PCOS) and cases where the woman’s eggs had become more resistant to conventional fertilization. ICSI was also being used in cases where sperm was absent (or virtually absent) from the ejaculate due to congenital or traumatic or medically acquired obstruction of the main collecting ducts (vasa deferentia), testicular failure and in cases where for traumatic, neurologic, or psychologi reasons (impotency) no semen/sperm was being ejaculated. In such cases, sperm obtained through Testicular Sperm Extraction (TESE), or aspiration (TESA) was being successfully used for ICSI. Today in the United states more than 70% of all IVF fertilizations are being conducted using ICSI with high fertilization and pregnancy rates being reported, regardless of sperm concentration, motility or morphology.
Clearly ICSI is increasingly replacing conventional insemination due to its many benefits and lack of definable drawbacks. In fact, pregnancy rates achieved by this method of fertilization are at least as high as those of conventional IVF performed in cases of non-male-factor infertility. Indeed, ICSI is associated with high fertilization and pregnancy rates regardless of sperm concentration, motility or morphology.
Notwithstanding, the above, the proposition that ICSI be preferentially used as the routine method for fertilizing eggs in IVF continues to meet with resistance. Die hards argue that about 1-3% of pregnancies resulting from ICS are associated with congenital developmental and genetic defects that affect the offspring. They cite conditions such as *Beckwith-Wiedemann syndrome, *Angelman syndrome, *hypospadias, sex chromosome abnormalities, a slightly increased miscarriage rate and the fact that male offspring resulting fom ICSI pregnancies are themselves at risk of subsequently developing male infertility in later life.
What you do not often hear from nay-sayers is that those studies that site the above mentioned risks do not distinguish between cases where ICSI is/was mandated for male infertility )and cases where ICSI is/was done for other (non-male infertility) reasons. If this was done, what in my opinion would emerge is that the above mentioned birth defects and developmental conditions are largely confined to the underlying male factor for which ICSI was indicated and are not due to the ICSI process itself. In fact a relatively recent study performed in Sweden demostrated this well. Here 542 children who were conceived naturally were compared with 941 children conceived through IVF (440 by conventional IVF & 541via ICSI) The babies/children were assessed at birth and during the first 5 years of life: The findings revealed that while the incidence of birth and developmental defects was indeed higher in ICSI babies, this only applied to cases where ICSI had been done for male infertility. It did not apply to cases where ICSI was done in the absence of male factor infertility.
Another very important consideration that supports the routine fertilization of eggs by ICSI is the fact that good quality IVF relies heavily on an ability to adequately assess egg maturation immediately following egg retrieval. To do this requires removal of layers of cumulus oophoris (CO) cells that cover the egg envelopment (zona pellucida). Only after the CO is stripped can the 1st polar body (PB-1) which is located immediately under the zona pellucida be identified and it is the presence of PB-1 signifies that indicates that the egg has gone through meiosis (reproductive division) and is thus mature (M2) and overwhelmingly, successful fertilzation and viable embryo development requires that the fertilized egg was mature (M2). This assessment for the presence of PB-1 cannot be reliably done without first removing the cumulus oophoris cells attached to the outer surface of the zona pellucida. The problem is that stripping the cumulus oophoris cells away, markedly reduces natural fertilization potential, leaving ICSI as the only alternative by which to subsequently achieve viable embryo propagation. The only way by which to avoid fertilization by ICSI would be to bypass the important step of assessing egg maturation and this in my opinion would compromize IVF outcome significantly. Thus optimization of the entire IVF process virtually mandates routine ICSI in IVF.
For the above reasons, I proudly count myself among a growing majority of IVF practitioners who support the routine use of ICSI for all IVF patients
*Angelman syndrome is a complex genetic disorder characterized by delayed development, intellectual disability, speech impairment, and problems with movement and balance (ataxia). Most cases are not inherited, particularly those caused by a deletion in the maternal chromosome 15 or by paternal uniparental disomy. These genetic changes are random events that take place during the formation of reproductive cells (eggs and sperm) or in early embryonic development.
*Beckwith-Wiedemann syndrome is a congenital growth disorder that causes large body size, large organs, and other symptoms. t results from a defect in the genes on chromosome 11. About 10% of cases can be passed down through families.
*Hypospadias: Hypospadias is a condition where the opening isn’t at the tip of the penis. Instead, it is located any place along the underside of the penis.
2. Would you recommend a blastocyst freeze, at all costs? Or is there any potential in a relatively weak 3-day embryo being put on ice?
I absolutely recommend blastocyst freezing preferentially for the following reasons: a) Embryos that fail yto reach the blastocyst stage of development are almost invariably abnormal and would not have propagated a viable pregnancy had they been frozen, anyway. b) The further along the embryo has developed, the safer the freezing process. c) Ultrarapidly frozen (vitrified blastocysts will in about 90% of cases survive the freeze- thaw in at least the same state of health as the day they were frozen and upon being transferred to a receptive uterus and will have at the very least the same ability to propagate a viable pregnancy as they would have done, had they been transferred fresh.
Hope this helps!
Geoff Sher
I am 33 years old female.
Is there any medicine to delay periods while on vacation so that I would not have to cancel the IUI cycle for that month
Yes, the period can be delayed with estrogen/progesterone hormonal therapy. Discuss with your gynecologist to effect.
Geoff Sher
I’m a 38 year old with two bio children ages 7 and 9. We started trying for number 3 but after 7 failed iui’s resulting in 2 ectopic pregnancies we’ve since moved to IVF. I’ve done 4 transfers. 2 with my eggs (not pgs tested, 4aa, 3bb and 4ab) and now two transfers with my 35 year old partners eggs (not tested all 5aa’s). All of my transfers have been painful. The doctor says my cervix is crooked and uterus severely retroverted. She is wondering if the transfer process is the problem and wants to do a transmyometrial transfer next round. We have 5 5aa embryos left. Is this a smart move? This seems like a rare procedure with a lower success rate. Are we missing anything else? Is a crooked cervix and retroverted uterus really causing all this trouble? Doesn’t explain the two ectopic pregnancies or am I just that unlucky to have multiple issues now when I got pregnant on the first try with each of my daughters. Any input would be appreciated.
Without examining you myself, I could not provide reliable recommendations. Transmyometrial ET’s work and I have done many, but it is undoubtedly preferable to use the conventional transcervical aproach.
Please call or email Julie Dahan, my patient concierge. She will guide you on how to set up an in-person or Skype consultation with me. You can reach Julie at on her cell phone or via email at any time:
Julie Dahan
•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.