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.
My wife was on Clomid for 5 months in 2015 from March to July. In 2016 she was on Clomid for another 4 months from March to June. While she was on Clomid in 2016, sonogram was taken twice and there were 2 follicles on the right ovary and there were no signs of hyper stimulation. It has been 2 months since she stopped taking Clomid. Now we are planning to go for IVF. I read that continuous stimulation of ovaries may cause ovarian cancer. Please tell us if the timing is right to go for IVF or should we wait for some more time before her ovaries can be stimulated again for IVF.
There is no truth to that concern. You should proceed!
Ever since January 1993 when a study was reported by researchers at Stanford University suggesting that the use of fertility agents increased the risk of ovarian cancer, there has been tremendous concern and anxiety among women who use fertility drugs. At first the findings seemed well founded because intuitively it made biological sense that fertility drugs might promote cancer because they increase the number of ovulations a woman has. And so the studies received wide public attention. It subsequently turned out that this study which was based on, data compiled from 12 retrospective studies on ovarian cancer patients done in the late seventies and early eighties was seriously flawed for the following reasons:
•While, retrospective (trohoc) studies have value in identifying an area of relevance for subsequent evaluation they are inadequate for reaching definitive conclusions. The only valid way to conclusively determine whether there is a link between prior use of fertility drugs and ovarian cancer would be through prospectively controlled statistical studies that compare the risk of ovarian cancer in infertile women who undergo ovarian stimulation with infertile women who do not.
•Infertile women who spend more than five years trying to conceive have about a 3 times higher risk for ovarian cancer than do fertile women. This is especially true when the infertility is due to absent or dysfunctional ovulation. Prior to the 90’s when the era of ovulation induction for intrauterine insemination (IUI) and IVF began to take off , the commonest indication for the use of fertility drugs was to induce ovulation in women who were not ovulating at all or normally. That all changed as more and more normally ovulating women started having IUI and IVF. Today, in 1st world countries, the number of normally ovulating women who receive fertility drugs exceeds those who receive such treatment because of absent or abnormal ovulation. Thus the emphasis has changed dramatically and with it, the risk of ovarian cancer has declined commensurately.
•Animal studies suggest that in contrast to gonadotropins, clomiphene citrate might after long and sustained usage, be carcinogenic. Since the 1993 Stanford University study data was derived at a time when most women undergoing COH were receiving clomiphene citrate (rather than gonadotropins), the possibility exists that the higher incidence of ovarian cancer might at least in part be due to this factor.
• The 1993 report did not take into account that pregnancy itself has a protective effect against the development of ovarian cancer. This means that those women who in fact conceived following the use of fertility drugs might through the occurrence of pregnancy have reduced their risk of subsequently getting ovarian cancer.
Most important is the fact that several large prospective studies have now refuted the existence of a link between the use of gonadotropins and ovarian cancer. On the other hand, there does appear to be an association between ovarian cancer and certain causes of infertility itself, such as endometriosis.
While the case is still out with regard to whether or not in humans the prolonged and repeated use of clomiphene citrate increases the risk of ovarian cancer, when it comes to the use of gonadotropins for controlled ovarian stimulation (COS) women can in my opinion, breathe easy.
Hope that helps!
Geoff Sher
Dear Dr Sher
I’ve read your very helpful and informative blog posts and comments on here about immunologic implantation dysfunction – thank your for sharing so much wisdom and guidance!
I miscarried (what tissue testing on the PoC revealed was) a euploid conceptus – immunes issues were therefore a key consideration in our post miscarriage investigations
These are the results of my NK Cells Cytoxicity K562 target test:
Method: Peripheral blood mononuclear cells (PBMCs) from the patient (effector cells) were co–cultured with K562 (NK sensitive) cells, labeled with CFSE (target cells), and incubated in a 96–well plate, at effector to target ratios of 50:1, 25:1 and 12.5:1 for 4 hours at 370C. The NK Cytotoxicity was evaluated in relation to the percentage of dead K652 after the subtraction of background cell death.
50:1 E:T NK Cytotoxicity 16.13% (normal range 26%-56%)
25:1 E:T NK Cytotoxicity 12.89% (normal range 15%-39%)
12.5:1 E:T NK Cytotoxicity 9.87% (normal range 12%-26%)
Results: The patient’s cytotoxicity level is below the normal range at all ratios.
The tests also included a TH1:TH2 assay
Method: Peripheral blood mononuclear cells (PBMC) were isolated by Ficoll–Hypaque and activated with PMA (50 ng/ml) and ionomycin (1µ?) in the presence of a transport inhibitor (i.e. brefeldin A). The produced cytokines were detected intracellularly, with fluorochrome conjugated antibodies by flow cytometry analysis. Percentages of Th1, and Th2 cytokine–producing cells were then identified as the number of CD3+CD4+IFN–?–positive, CD3+CD4+TNFa–positive and CD3+CD4+ IL–10–positive cells present, in the total population of PBL (CD45+ cells).
Results: Th1/Th2 Intracellular cytokine ratios
CD3+CD4+IFN?+ 0.84 %
CD3+CD4+??Fa+ 3.87 %
CD3+CD4+IL–10+ 0.14 %
Ratios
(CD3+CD4+)IFN?/IL–10 6.00% (normal range 5.8%-20.5%)
(CD3+CD4+)??Fa/IL–10 27.64% (normal range 13.2%-30.6%)
Comments:
The results show that the (CD3+CD4+)IFN?/IL–10 and (CD3+CD4+)??Fa/IL–10 ratios are marginally above the low typical range and within the normal range, respectively. Our control sample was within the typical range.
Do you see anything here that concerns you from an NKa point of view?
Warmest regards
Katy
Very respectfully, I totally disagree with the interpretation of these test results. In my opinion, the NKa level is elevated. Anything above 10% is suspect and so is the TH-1 cytokine level suspect. In fact, I strongly suspect that you do have an immunologic implantation dysfunction (IID). What bothers me is the way the NK activity is reported. It leads me to suspect that the methodology used is not the standardized approach. I suggest that you repeat the K-562 test at another reproductive Immunology Reference laboratory. I would suggest your using Reproductive Immunology Associates (RIA) in Van Nuys, CA. Look up there contact information on Google, call them and mention my name. I would also have them do an immunophenotype, antiphospholipid and antithyroid antibody analysis on your blood I would omit doing a cytokine analysis. I would also suggest that you have RIA do a DQ alpha/HLA Genotypic assessment done on your and your husband’s husband’s blood to look for alloimmune matching as this would affect treatment.
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.
•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
•Ovarian Stimulation for IVF using GnRH Antagonists: Comparing the Agonist/Antagonist Conversion Protocol.(A/ACP) With the“Conventional” Antagonist Aproach
•Why did my IVF Fail
•IVF Failure and Implantation Dysfunction:
•The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
•Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
•Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
•Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
•Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report
•Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
•Intralipid (IL) Administration in IVF: It’s Composition; How it Works; Administration; Side-effects; Reactions and Precautions
•Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
•Endometrial Thickness, Uterine Pathology and Immunologic Factors
•Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
•Traveling for IVF from Out of State/Country–
•A personalized, stepwise approach to IVF
•The Role of Nutritional Supplements in Preparing for IVF
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.
Hi there
I’m getting my eggs frozen this month. I was to get an ultra sound on day 2 of my period and begin the injections starting day 3 if all looks well on the ultra sound. I ended up starting to feel symptoms this past Friday for my period however I don’t have my ultra sound booked until this upcoming Thursday. I went into my pharmacy and got ortho tri cyclen ( a b/c that has .25mg nordestimate and .035mg ethinyl estradio) to try and delay my period until Wed. It’s a long weekend ,Monday is a holiday in Canada. Today is Sunday and even though I’m on the ortho tri cyclen I have noticed spotting. I cannot get in touch with my doctor to see if I should continue the bc or stop. Will starting my Injections on day 5 hinder my outcome for eggs?
Hi Alexis,
I really cannot comment authoritatively here because I have no idea what sort of protocol your RE is planning gto use.
So so sorry!
Geoff Sher
Dear Dr Sher,
If a person naturally has high FSH of 20 on CD2 isnt it the same as a patient having low FSH 5 naturally on CD2 and giving 450iu of FSH? Either way patient gets high FSH on CD2 either naturally or medically? So why bother so much to get FSH low on CD2 only to raise it with meds?
In my opinion, it is not so much about getting the FSH low. Rather it is about keeping LH low because a high LH early on in the stimulation can compromize egg development by increasing ovarian testosterone.
Geoff Sher
Dear Dr Sher,
What causes a cycle to be longer than usual? Generally my cycles are 28 days and once in awhile it takes 18 days to ovulate when normally I ovulate on 13th day of each cycle. I am curious to know what causes sudden difference in length.
Menstruation usually occurs about 14v days after ovulation. If ovulation occurs later, the period will usually be delayed.
Geoff Sher