The question
Dear Dr Sher, I live in Israel, am 40 years A old and having frozen embryo created with donor eggs as I have no ovarian reserve. No previous pregnancies or miscarriages.
My endomerial lining measured on day 4 of my period was 1.4 mm. I was told to take Estrofen 3/4th day after start of period for 1 week and to have new ultrasound for measuring endometrium lining. Given the 1.4 mm thickness on day 4 of my period, I do not think that Estrofen is the best choice to get the required 8 or 9 mm for embryo transfer. Please could you recommend what medicine is more likely to provide maximum thickning of the endometrium? Thank you so much. Ayelah
Answer from Dr. Geoffrey Sher
I need to have more information. An important consideration is "how long have you been estrogen-depleted". IOW how long have you been not having periods (amenorrhea). The reason I say this is that women who have been anesgtrogenic for >6moths, often have depletion of endometrial estrogen receptivity and will not develop an adequate estrogen-induced lining until they have had cyclical HRT for at least 3-4 months. This wil reactivate estrogen receptivity and solve the problem. There could be other reasons for a non-receptive endometrium as well...see below).
My preference for hormonal endometrial stimulation is as follows:
- Cycle Start: To begin, t birth control pills (like Marvelon, Desogen ,Lo-Estrin etc.,)for about 10 days. Then patient commence 0.75mg Dexamethasone daily OR 10mg prednisone BID at cycle start. This is continued to the 10th week of pregnancy (tailed off from the 8th to 10th week) or as soon as pregnancy is ruled out
- Hormone Kickstart: After 10 days on BCP , start daily injections of a GnRH antagonisd (e.g., upron/Lucrin/decapeptyl/ Superfact/ Buserelin) .
- Monitoring Progress: Ultrasounds and blood tests done serially.
- Hormone therapy: Delestrogen (estradiol valerate-E2V) 4mg IM is injected, twice weekly (on Tuesday and Friday), commencing within a few days of Lupron/Lucrin/Superfact, Decapeptyl-induced menstruation. Blood is drawn on Monday and Thursday for measurement of blood [E2]. This allows for planned adjustment of the E2V dosage scheduled for the next day. The objective is to achieve a plasma E2 concentration of 500-1,000pg/ml and an endometrial lining of >8mm, as assessed by ultrasound examination done after 10 days of estrogen exposure i.e., a day after the 3rd dosage of Delestrogen. The twice weekly, final (adjusted) dosage of E2V is continued until the 10th week of pregnancy or until pregnancy is discounted by blood testing or by an ultrasound examination. Dexamethasone/Prednisone is 0.75 mg is taken orally until the 10th week of pregnancy.and oral folic acid (1 mg) is taken daily commencing with the first E2V injection and is continued throughout gestation.
- Antibiotic prophylaxis: Ciprofloxin 500mg BID orally starting with the initiation of Progesterone therapy and continuing for 10 days.
- Luteal support: commences on 6 days prior to the FET, with intramuscular progesterone in oil (PIO) at an initial dose of 75-100 mg (-Day 1). Daily administration- is continued until late in the evening of Day 5 ( I suggest 10.00PM-11.00PM) . Daily PIO (75mg-100mg) is continued until the 10th week of pregnancy, or until a blood pregnancy test/negative ultrasound (after the 6-7th gestational week), discounts a viable pregnancy. Also, commencing on the day following the FET, the patient inserts one (1) vaginal progesterone suppository (100 mg) in the morning + 2mg E2V vaginal suppository (in the evening) and this is continued until the 10th week of pregnancy or until pregnancy is discounted by blood testing or by an ultrasound examination after the 6-7th gestational week.
- Blood pregnancy Testing: Blood pregnancy tests are performed 13 days and 15 days after the first PIO injection was given
- Timing the FET: This is performed as early as possible on the morning of Day-6
Hope this helps. If you wish to talk to me, call my assistant, Patti Converse (702-533-2691) and set up an online consultation to discuss.
Geoff Sher
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- THE IMPACT OF A THIN UTERINE LINING ON EMBRYO IMPLANTATION: THE BENEFITS OF VIAGRA THERAPY
Back in 1989, I conducted a study that examined how the thickness of a woman's uterine lining, known as the endometrium, affected the successful implantation of embryos in IVF patients. The study revealed that when the uterine lining measured less than 8mm in thickness by the day of the "hCG trigger" in fresh IVF cycles, or at the start of progesterone therapy in embryo recipient cycles (such as frozen embryo transfers or egg donation IVF), the chances of pregnancy and birth were significantly improved. In my opinion, an ideal estrogen-promoted endometrial lining should measure at least 9mm in thickness, while a lining of 8-9mm is considered "intermediate." In most cases, an estrogenic lining of less than 8mm is unlikely to result in a viable pregnancy.
A "poor" uterine lining typically occurs when the innermost layer of the endometrium, called the basal or germinal endometrium, fails to respond to estrogen and cannot develop a thick enough outer "functional" layer to support optimal embryo implantation and placenta development. The "functional" layer makes up two-thirds of the total endometrial thickness and is the layer that sheds during menstruation if no pregnancy occurs.
The main causes of a "poor" uterine lining include:
- Damage to the basal endometrium due to:
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- Inflammation of the endometrium (endometritis) often resulting from retained products of conception after abortion, miscarriage, or birth.
- Surgical trauma caused by aggressive uterine scraping during procedures like D&C.
- Insensitivity of the basal endometrium to estrogen due to:
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- Prolonged or excessive use of clomiphene citrate.
- Prenatal exposure to diethylstilbestrol (DES), a drug given to pregnant women in the 1960s to prevent miscarriage.
- Overexposure of the uterine lining to ovarian male hormones, mainly testosterone, which can occur in older women, women with diminished ovarian reserve, and women with polycystic ovarian syndrome (PCOS) who have increased LH biological activity. This hormonal imbalance leads to the overproduction of testosterone in the ovary's connective tissue, further exacerbated by certain ovarian stimulation methods used in IVF.
- Reduced blood flow to the basal endometrium, often caused by:
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- Multiple uterine fibroids, especially those located beneath the endometrium (submucosal).
- Uterine adenomyosis, an abnormal invasion of endometrial glands into the uterine muscle.
"The Viagra Connection"
Eighteen years ago, I reported on the successful use of vaginal Sildenafil (Viagra) in treating women with implantation dysfunction caused by thin endometrial linings. This breakthrough led to the birth of the world's first "Viagra baby." Since then, thousands of women with thin uterine linings have been treated with Viagra, and many have gone on to have babies after multiple unsuccessful IVF attempts.
Viagra gained popularity in the 1990s as an oral treatment for erectile dysfunction. Inspired by its mechanism of action, which increases penile blood flow through enhanced nitric oxide activity, I investigated whether vaginal administration of Viagra could improve uterine blood flow, deliver more estrogen to the basal endometrium, and promote endometrial thickening. Our findings confirmed that vaginal Viagra achieved these effects, while oral administration did not provide significant benefits. To facilitate treatment, we collaborated with a compound pharmacy to produce vaginal Viagra suppositories.
In our initial trial, four women with a history of poor endometrial development and failed conception underwent IVF treatment combined with vaginal Viagra therapy. The Viagra suppositories were administered four times daily for 8-11 days and stopped 5-7 days before embryo transfer. This treatment resulted in a rapid and significant improvement in uterine blood flow, leading to enhanced endometrial development in all four cases. Three of these women subsequently conceived. In 2002, I expanded the trial to include 105 women with repeated IVF failure due to persistently thin endometrial linings. About 70% of these women responded positively to Viagra therapy, with a notable increase in endometrial thickness. Forty-five percent achieved live births after a single cycle of IVF with Viagra treatment, and the miscarriage rate was only 9%. Women who did not show improvement in endometrial thickness following Viagra treatment did not achieve viable pregnancies.
When administered vaginally, Viagra is quickly absorbed and reaches the uterine blood system in high concentrations. It then dilutes as it enters the systemic circulation, explaining why treatment is virtually free from systemic side effects.
It is important to note that Viagra may not improve endometrial thickness in all cases. Approximately 30-40% of women treated may not experience any improvement. In severe cases of thin uterine linings where the basal endometrium has been permanently damaged and becomes unresponsive to estrogen, Viagra treatment is unlikely to be effective. This can occur due to conditions such as post-pregnancy endometritis, chronic inflammation resulting from uterine tuberculosis (rare in the United States), or extensive surgical damage to the basal endometrium.
In my practice, I sometimes recommend combining vaginal Viagra administration with oral Terbutaline (5mg). Viagra relaxes the muscle walls of uterine spiral arteries, while terbutaline relaxes the uterine muscle itself. The combination of these medications synergistically enhances blood flow through the uterus, improving estrogen delivery to the endometrial lining. However, it's important to monitor potential side effects of Terbutaline such as agitation, tremors, and palpitations. Women with cardiac disease or irregular heartbeat should not use Terbutaline.
Approximately 75% of women with thin uterine linings respond positively to treatment within 2-3 days. Those who do not respond well often have severe inner ( (basal) endometrial lining damage, where improved uterine blood flow cannot stimulate a positive response. Such cases are commonly associated with previous pregnancy-related endometrial inflammation, occurring after abortions, infected vaginal deliveries, or cesarean sections.
Viagra therapy has been a game-changer for thousands of women with thin uterine linings, allowing them to successfully overcome infertility and build their families.
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ADDITIONAL INFORMATION:
Herewith are online links to 2 E-books recently co-authored with my partner at SFS-NY (Drew Tortoriello MD)....... for your reading pleasure:
- From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) ; https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf
- Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link ;https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view
If you are interested in having an online consultation with me, please contact my assistant, Patti Converse at 702-533-2691 or email her at concierge@sherivf.com\
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General information only, not medical advice for your own situation. For that, book a consultation.