SCIENCE PULSE    Using Frozen Sperm for IUI

Many of our patients are undergoing fertility treatment for male factor indications, and undergo insemination therapy. This may be patients who are using donor sperm from a sperm bank, or patients who are using their partner’s sperm, but the sperm has been frozen (partner out of town, or other indications). We are often asked if the success rates will be affected by the use of frozen versus fresh sperm. As well, we are asked if the number of inseminations performed per cycle will affect the success rates. There is a body of studies that have been done to address these specific questions, and our clinic’s interpretation of the literature is the following.

The first consideration addresses which type of insemination provides the best outcome when using frozen sperm. A number of studies have looked at this question, and when all the data from those studies are compiled and analyzed, results indicate that if an intrauterine insemination (IUI) is performed (sperm placed directly in the uterus), the odds are 2.5 times greater that a pregnancy will occur, than if an intracervical insemination (ICI) is performed (sperm placed at the entrance of the cervix) (5% vs. 14% monthly chance of pregnancy) (1, 2). When sperm are placed at the cervix, many of them are “lost” as they travel through the cervix and into the uterus, to then find their way to the fallopian tubes. This dilutes the actual numbers that make it to the egg in the fallopian tube, and therefore decreases chances of success. Performing 2 intracervical inseminations in one cycle (9% chance of pregnancy) did not bring success rates close to what one intrauterine insemination achieved (15% monthly chance of pregnancy) (2).

Next consideration addresses if fresh sperm is better than frozen sperm. Two studies have addressed this best, and indicate that the critical components that will provide comparable pregnancy rates are the performance of an intrauterine insemination (IUI), accurate timing of the insemination (relative to the ovulation event), and adequate concentration of sperm inseminated (called total motile count=TMC) (3, 4). The most accurate way to time the insemination is by using ovulation predictor kits (OPK), or by administration of an HCG injection to trigger the ovulation event. Ovulation predictor kits have been evaluated and the kit we recommend is the Clear Blue Easy ovulation kit. First detection of an LH surge is most likely to occur in the morning, and our recommendation is to do one test/day, in the morning (5). The best timing for an intrauterine insemination using frozen sperm is within 24-28 hours after a positive LH surge as detected by an Ovulation Predictor kit. In a well-designed study, using first positive OPK results to time insemination, 5% of total pregnancies resulted in cycles where the IUI was done within 24 hours of the positive OPK result, 90% of total pregnancies if within 24-48 hours, and 5% of total pregnancies if past 48 hours (5). Quite a few studies have evaluated the minimum number of inseminated sperm required to achieve an adequate pregnancy rate. Most indicate a total motile count between 6-15 million. This means that after thawing the frozen sperm specimen, the lab must recover between 6-10 million moving sperm. Most sperm banks provide a post thaw guarantee of 10-15 million/vial if prepped for an IUI (sperm already washed), or 15-20 million/vial if prepped for an ICI (unwashed sperm).

Next consideration addresses sperm washing techniques. There are a number of different laboratory techniques for washing and preparing sperm for insemination. As it turns out, there is no difference in pregnancy rates based on the sperm preparation technique. This holds for both the freezing technique and the post thaw washing technique (if ICI prepped) (6). This also applies if the sperm is pre-washed by the laboratory prior to freezing (if IUI prepped) (7). As long as an adequate TMC is reached post freeze-thaw, pregnancy rates hold steady.

The last consideration is: would one IUI per cycle reach adequate pregnancy rates, or would 2 IUI’s be better? Many studies have been done evaluating this question, and while individual studies may show different results, the majority of studies indicate that one IUI/cycle is adequate, and 2 IUI’s does not improve pregnancy rates, as long as the IUI is well timed, and the TMC inseminated is adequate (2, 8, 9, 10, 11).

In conclusion: We take guidance from the best published literature, and use the following guidelines for managing frozen sperm intrauterine insemination cycles at Pacific Fertility Center:

• Determine best timing of intrauterine insemination or IUI:
  First positive ovulation predictor kit (OPK) if OPKs are reliable, or HCG injection as administered according to our instructions.
• Do one IUI 24-48 hours after first positive OPK, or 24-48 hours after administration of HCG
• Do intrauterine insemination (not intracervical insemination or ICI)
• Assure insemination with adequate total motile count or TMC
  We will thaw sperm until we have a TMC of 10 million

Footnotes

1. Goldberg et al, Fertil Steril. 1999 Nov; 72(5):792-5

2. Carroll et al, Fertil Steril. 2001 Apr:75(4):656-60

3. Subak et al, Am J Obstet Gynecol. 1992 Jun; 166:1597-604

4. Bordson et al, Fertil Steril. 1986 Sept;46(3):466-9

5. Khattab et al, Hum Reprod. 2005 Sep;20(9):2542-5

6. Byrd et al, Fertil Steril. 1994 Oct;62(4):850-6

7. Wolf et al, Fertil Steril. 2001 July;76(1):181-5

8. Centola et al, Fertil Steril. 1990 Dec;54(6):1089-92

9. Lincoln et al, J Assist Reprod Genet. 1995 Feb;12(2):67-9

10. Khalifa et al, Hum Reprod. 1995 Jan;10(1):153-4

11. Matilsky et al, J Androl. 1998 Sept-Oct;19(5):603-7

 Isabelle Ryan, MD is recognized by prestigious medical associations for her pioneering research leading to new insight into the important clinical problem of endometriosis related infertility. At PFC she remains active in research while enjoying caring for infertile patients. She has been singled out by her peers as a “Top Doctor” in physician surveys. Dr. Ryan directs PFC’s Third Party Parenting Program and our in-house egg donor agency.

ASK THE EXPERTS    Gender Selection

  Pacific Fertility Center Team
Left to Right: Front: Philip Chenette, MD, Isabelle Ryan, MD, Carolyn Givens, MD
Back: Joe Conaghan, PhD, Carl Herbert, MD, Eldon Schriock, MD

Question: My husband and I have two boys and want to have a girl.
What are our options?

Answer: Gender selection is a complicated and difficult issue. Ethics aside, there really are only two proven methods. The first is a technique of sorting sperm cells called Microsort. If there is a healthy number of motile sperm present (no significant male infertility), the husband can fly to Southern California to the Microsort lab and have the sperm sorted. That sperm can then be used to inseminate the wife at Huntington Reproductive Center in Laguna Hills or can be frozen and shipped back to PFC for use in IVF. Because the technique results in such poor recovery of sperm, insemination may take several tries. This is why most of our patients will use the sperm in conjunction with IVF, in which case we can inseminate by single sperm injection (ICSI) several of the wife’s eggs, producing and then transferring embryos back to the uterus, and giving the couple a better chance of success. The sperm sorting method is much more efficient if the gender desired is female (see Microsort Facts below). We receive a report from Microsort about the estimated percentage of sperm that are X-bearing (female) vs. Y-bearing (male). Usually, for a female, that is about 85% and most couples interested in a girl are comfortable with those odds. For a male, the odds are lower (about 73%) and therefore, if a boy is really desired, most couples look to PGS (Pre-Implantation Genetic Screening).

With PGS, the patients undergo IVF with ICSI to create the embryos, and when the resulting embryos have 5-8 cells, a single cell is removed and analyzed for a number of chromosomes, including X and Y. If the couple wishes to transfer only the embryos of one gender, they will have to decide what to do with the remaining embryos. The technique is close to 93% accurate, which is a huge advantage over Microsort if male gender is desired. However, our most recent statistics with PGS indicate implantation rates tend to be lower. We do suspect that the procedure of removing a cell from the embryo may be decreasing the chances of successful implantation.

There are many more complex issues involved with PGS so we require our patients considering this process to meet with a genetics counselor (we work with the Perinatal Genetics program at California Pacific Medical Center for this counseling) to discuss the implications of undergoing this process in more depth.   Carolyn Givens, M.D.

Microsort Facts • Sperm sorting technique

Two locations: Virginia and Southern California

Must be younger than 40 years old (or using egg donor)

Must be for Family Balancing (not first child)

Low % of sperm recovered

Efficiency for a girl is about 85%

Efficiency for a boy is about 73%

For more info, visit the website: www.microsort.net

FROM US TO YOU    New Office Manager

 Pacific Fertility Center (PFC) is pleased to announce the arrival of new Office Manager, Sasha Eppel. Sasha joined the PFC team in March after working at UCSF’s Medical Center for five years in the Gastroenterology outpatient department. As Office Manager at PFC, Sasha makes sure that the inner-workings of the office run smoothly, overseeing the medical records and front desk staff as well as facility issues.

• Providing a welcoming, positive environment when patients arrive for appointments and wait in the lobby.
• Ensuring that calls from current PFC patients are answered promptly and routed appropriately.

• Ensuring that medical records are archived and easily accessible.
• Ensuring office and physician staff are available 24 hours a day, 7 days a week to address the urgent needs of both patients and physicians.
• Routing urgent requests from physician’s offices to the appropriate PFC staff to facilitate prompt and accurate responses.

“During office visits, our department is the initial point of contact for patients. I believe it is important that we provide a calming atmosphere through patience and understanding,” commented Sasha.

A lot of the work Sasha performs at PFC is “behind the scenes,” and not necessarily visible to outsiders. For instance, it is her primary responsibility to update physician schedules. This can be a balancing act—one must provide ample time for patient appointments all the while making time for staff meetings to discuss key issues facing the practice.

The value of patient scheduling cannot be understated. Time is of the essence for fertility patients and, in many cases, the sooner they make their appointments, the better. PFC physician schedules are done well enough in advance to ensure that patients can quickly come in for appointments yet are given ample time to complete preliminary testing and obtain their medical records.

For Sasha, being a member of the PFC team has proved rewarding—specifically by helping make a difference in the overall patient experience. Moreover, PFC combines the latest in reproductive technology with a warm, personal approach to patient care. This takes on added significance as many patients come to PFC after having had years of frustration and stress associated with infertility.

PATIENT ODYSSEY    Expecting Soon

  For my husband Matthew and me, hard work had always paid off. We had led successful professional careers, thanks to our diligence and work ethic. We approached having a child the same way but, to our dismay, we were unable to conceive for over two years. When it came to finding a fertility solution, I had been pretty resistant to assisted reproductive technology (ART). I’m a firm believer in natural approaches such as herbs and acupuncture and favored them as a pregnancy solution as opposed to medical intervention. Yet, we were running out of options. I was going to turn 40 years old. Time wasn’t on our side.

Overcoming infertility was an emotionally draining ordeal for my husband and me. Thankfully, we weren’t in it alone. Friends and family were very understanding of our plight. In fact, my brother and his wife were also trying to become parents. However, with some friends who had children, it was difficult to convey the physical and emotional challenges we were going through. After all, parents who hadn’t experienced delays in conceiving couldn’t relate to our journey. We were happy for our friends who had children but did wonder to ourselves, “Why weren’t we yet blessed with a child?”

Ultimately, my husband and I decided to pursue ART. My OB/GYN encouraged me to contact Dr. Givens at Pacific Fertility Center (PFC). We were anxious, hopeful, and curious about the opportunities available to us at PFC. At the same time, we knew we were going to be in for an emotional roller coaster. Dr. Givens was fabulous. She was straightforward and medically professional in her approach. She was also compassionate about our endless array of questions and emotional highs and lows.

Although there was initial disappointment after two unsuccessful IUI attempts, it was short-lived. After just six short months, we moved on to IVF, and became pregnant on our first try. We were happy with this news but tempered our enthusiasm, as we weren’t sure if the baby would make it through the first trimester. Our happiness turned into pure elation after the amniocentesis, as we then knew for sure that our baby was healthy.

I can’t say enough about the caring and responsive team at PFC. From the administrative support staff, to the financial/accounting staff, to the training crew, to the nurses, to the doctors, everyone took great care in addressing our individual concerns. I also sought Dr. Givens’ attention in asking her to put me in touch with a patient who had successfully conceived through ART. I was in constant contact with this patient throughout my cycles and her insight was invaluable. She helped me understand the journey to pregnancy and gave me emotional support.

We are now huge advocates of ART – especially for couples who have tried for some time to get pregnant. Nevertheless, I do feel that the holistic approach of taking herbs and acupuncture was helpful in preparing my body for pregnancy. Our advice to those trying to conceive is to seek advice/treatment from PFC, work with the staff to learn what the medical reality is for you and/or your partner, and then move forward. I also think it would be helpful for couples to speak directly with other couples who have pursued infertility treatment, so that they know they are not alone.

The journey to pregnancy has made us realize that we must be collaborative and supportive of each other’s feelings. If I could give some additional advice to couples and individuals dealing with infertility, it would be to have open and honest communication with your partner, friends and family. This can be very cathartic.

Today, we feel that we are prepared to be the best parents ever. We want to create the most loving and supportive atmosphere possible for the child we are expecting, regardless of how difficult being a new parent might be. Certainly parenthood won’t be easy but the joy we’ll experience as parents will more than make up for it. The baby is due in mid-March, and, as you can imagine, we feel blessed and elated!  Felicia (Names were changed at the author’s request.)

Postscript: Matthew and Felicia have a new member to their family. On March 6, 2006 Felicia gave birth to a happy, healthy Baby Maria. Congratulations!

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-- Best regards from all of us at Pacific Fertility Center.