Spring, a time for celebrating Mothers and Fathers, can be a particularly difficult time for infertility patients. Because dealing with these two holidays can be a challenge, I have some suggestions for ways to develop some good coping skills. To cope is to “develop the ability to manage in a difficult situation.”

Here are a few suggestions:

1. Give up any and all feelings of guilt for how you are feeling! There is no right or wrong way to experience Mother or Father’s Day.
2. Know your limits and stick with them. If attending a family gathering is too painful, then don’t. You can still write a caring letter to your parent letting them know how you feel about them. If you do feel comfortable attending a family gathering, then do.
3. Plan to do something that is unrelated to parenting.
4. Attend religious services if you are comfortable knowing that the focus may be on mother’s or fathers. Perhaps you can ask your religious leader to say a prayer for those who have not yet achieved parenthood or are dealing with some other sort of crisis.
5. Plan for how you will answer uninvited questions about how you are feeling. Remember, you are not required to tell them your entire “story!”
6. Communicate with your partner to let him/her know of your feelings. Even if you and your partner are feeling differently about Mother’s or Father’s Day, it may help to share. If you are single, call a friend with whom you feel safe to share your feelings.
7. If you think it might be helpful, please call the clinic and set up an appointment with me, at no charge. Our number is 415-834-3000.

– Peggy Orlin, MS, MFT

This past summer, I had the opportunity to travel to Amsterdam, Holland for the annual meeting of the European Society for Human Reproduction and Embryology (ESHRE). Though largely attended by Europeans, this scientific meeting draws physicians, embryologists and scientists from around the world to discuss their research, attend courses and lectures, and discuss the latest topics in our field. Although I don’t think this year’s meeting was as quite as good as last year’s ESHRE in Barcelona, there were still some good learning opportunities. Here are some of the highlights of the meeting:

“From Gamete to Heartbeat: The Missing Link”

This was a post-graduate course offered in conjunction with the meeting. The course covered sperm and egg evaluation,

expression of genes in the early embryo and in the endometrium (uterine lining) and some of the latest research into basic embryo implantation mechanisms.

One of the interesting talks was on gene expression in the early embryo. We have come to believe that the differences in pregnancy rates between younger and older women is mainly due to an increase in the number of abnormal chromosomes in embryos from women as they age (such as increased risk for Down Syndrome). However, this only explains part of the differences in successful pregnancy in younger compared to older mothers. New research into expression of proteins from embryonic genes is showing that in both chromosomally normal and abnormal embryos, there are differences in the number and types of genes encoding proteins in younger and older women. This suggests that it is not just changes in the number of chromosomes but subtler differences in the way individual genes are being expressed that affect the developmental competence of their embryos. Determining which genes and proteins are involved, and what the mechanisms are for regulating the expression of these genes in early embryos, will be an area of focused research in the coming years.

“Hyaluronic Acid (HA) favors selection of spermatozoa with intact DNA and normal nucleus, resulting in improvement of embryo quality” (Bologna, Italy)

This presentation (Parmegiani, et al.) looked at the percentage of sperm showing DNA fragmentation based on several methods of sperm preparation for IVF-ICSI (in vitro fertilization with intracellular sperm injection). They compared sperm in the fresh specimen 30 minutes after ejaculation, sperm that had been processed with a standard “swim-up” technique, and sperm that were placed in PVP (polyvinyl propylene), a substance used to slow sperm down so they can be picked up from a culture dish just prior to injection into the eggs. Lastly, they looked at sperm that had been placed into dishes that contain a ring of hyaluronic acid at the bottom of the dish, a substance to which some sperm will automatically bind. They looked at the percentage of sperm showing total or partial fragmentation of the DNA with each of these steps in the sperm preparation process. In the freshly ejaculated sperm, the DNA fragmentation was 16.5% of tested sperm. In the “swim-up” sperm prep, 11% were fragmented and in the PVP-exposed sperm, it was also 11%. Sperm that had bound to hyaluronic acid showed the least amount of fragmentation, at 5.3%.

These findings suggest that using HA binding to select sperm for sperm injection may result in fewer abnormalities in embryos, and possibly higher pregnancy rates. PFC is currently investigating HA binding on our own to see if it is something we would wish to routinely incorporate into IVF. The downside (like everything else!) is that HA plates are expensive.

Stress and Fertility – an enlightening symposium

Jacky Boivin, PhD., a researcher from Cardiff University in Wales, presented some very interesting data about the stresses of infertility treatment. She discussed a new study from Alice Domar’s group in Boston that surveyed why women/couples discontinued IVF treatment before achieving pregnancy (Fertility and Sterility, in press 2009). In this study, 132 women who had insurance coverage for IVF were surveyed. The two main reasons given for dropping out of treatment were the toll that infertility took on the couples’ relationship and being too anxious or depressed to continue. Among the less common reasons for dropping out were medication-related issues (such as difficulty with injections) and feeling the need for a female doctor. Dr. Boivin also discussed results from her own study that was published in the journal Human Reproduction in 2008. In that study, she developed a copingstratagem for women awaiting results of their treatment (i.e. the time between embryo transfer and first beta hCG). It is known that this is a most anxious time for women and the stress of waiting can become overwhelming. She utilized something called the “positive reappraisal coping intervention” card, or “PRCI” card. This is a small printed card that a patient can carry around in his or her pocket and it is meant to be read 2 times per day, every day during the 9-11 days between embryo transfer and first pregnancy test. The card has several little sayings such as: “During this experience I will try …to do something that makes me feel positive” and “During this experience I feel that….I’m energized or I’m creative.” This is a way of programming thoughts towards the positive and away from the negative. She and her colleagues were able to show that patient felt less stressed and felt that the PRCI was helpful during this period.

Currently, at PFC, we have begun a task force to look into ways to better incorporate counseling and tools for stress management for our patients. Please also see this recent Patient Odyssey. Support groups are a wonderful way to diffuse stress and feel more positive.

Corifollitropin: a modification of Follistim to allow a once-a-week injection.

As most people know, the medication we most commonly use for fertility treatment, Follistim, is pure human FSH, manufactured using recombinant DNA technology. The company that makes Follistim, Schering Plough, is working towards FDA approval of a modified version of Follistim, called Corifollitropin, that will make the drug very long-acting.

For those interested in the details; Corifollitropin is the recombinant FSH molecule + 22 C-terminal peptides from betahCG. It does not bind to the LH receptor. This modification lengthens the half-life of Follistim from 22-34 hours to 60-74 hours for Corifollitropin. The recommended regimen will be one dose per week, starting at baseline, then switch to daily recombinant FSH after that. After injection, peak levels are reached in 2 days then they slowly level. It may be possible to only take one injection per week!

A symposium at ESHRE presented information from the ENGAGE trial with data from 14 European and 5 Asian IVF centers, using women with body mass indices (BMIs) between 18 and 32 (generally less than 60 kg -132 lb). The patients were randomized to receive either Corifollitropin or conventional daily recombinant FSH for oocyte recruitment. The number of days of stimulation was the same in both groups (9). The number of eggs retrieved was significantly higher in the Corifollitropin group (13.3) vs. the FSH group (10.6). The rates of ovarian hyperstimulation syndrome were the same in both groups (about 3%). The pregnancy rates were 25% in the Corifollitropin group and 34% in the FSH group, a difference that did not quite reach statistical significance.

Data were also presented on a second study of Corifollitropin from the U.S. and Europe, comparing two doses of the drug. In the study, 100 mcg/dose was given to women less than or equal to 60 kg and women greater than 60 kg were dosed at 150 mcg. Over 1500 patients were included in this large trial. In this study, the average number of eggs recovered was 13.7 for the Corifollitropin group and 12.5 for the Follistim group. The mature egg and fertilization rates were the same. The percentage of good quality embryos was the same.

The clinical pregnancy rate in the Cori group was 38.9% and was 38.1% in the Follistim group. These rates were statistically the same. We expect that Corifollitropin will likely be available in the U.S. in 2010 or 2011.

Mind/body therapies are frequently initiated for groups with serious medical conditions, from lupus to multiple sclerosis to major heart disease. It is only natural that the more critical an illness, the more anxiety it can induce, thus potentially inducing accelerated and aggravated symptoms. Breaking this vicious stress/body cycle through the use of stress reduction techniques can provide an overall improvement in health. For those experiencing infertility, the hope is that breaking this cycle would lead to an improved ability to conceive.

Skeptics point out that millions of people, under extremely stressful circumstances, regularly get pregnant. But some facts are clear: ongoing chronic stress can affect menstrual function; change hormone levels; alter blood sugar; increase heart rate and change a person’s immune response.

Pacific Fertility Center’s team has examined the scientific, medical and anecdotal information surrounding the topic of stress and infertility. We have found that various stress reducing techniques are likely to have an overall positive impact on a patients’ general health. For this reason, PFC continues to offer classes modeled around Dr. Alice Domar’s mind/body practice (see PacificFertilityCenter.com for more information on Dr. Domar and Mind/Body@PFC Workshops).

Alice Domar, PhD has extensively probed the mind/body infertility correlation. She initiated one of the few controlled studies funded by the National Institute of Mental Health on this topic. Results of the research showed an improvement in pregnancy rates through the use of either relaxation techniques or the psychological support of joining a group. Based on the results of her research, Dr. Domar’s mind/body programs include instruction on relaxation techniques, controlled breathing and posture awareness; yoga, meditation, journaling, neuro-linguistic programming, and the joining of a support network. These techniques are designed to help women adjust their stress responses so their bodies might have a higher chance of conceiving.

It is our hope that the growing attention to the mind/body stress reduction methodologies will lead to the development of more critical scientific knowledge on the topic. Meanwhile, take a deep breath and review Peggy Orlin’s tips on relieving stress during this holiday season.  Carolyn Givens, MD and Isabelle Ryan, MD

Coping is developing the ability to manage in a difficult situation.
Excited children, crowded stores, decorations, and holiday parties are descending upon us. Yet because the winter holidays tend to celebrate families and children, these usually joyous occasions can bring up painful feelings when you are struggling to create and celebrate with a family of your own. In order to feel as good as possible during the holidays, you will need to develop some good holiday coping skills. Use whichever of these suggestions seem helpful to you. Do what feels right for you.

DO: Give up any and all guilt for how you are feeling. There is no right or wrong way to experience infertility. Your feelings may run the gamut from indifference to intense anger and despair and everywhere in between.

DO: Reach out to childfree friends. Their parties will be adult-focused.

DO: Choose the gatherings you attend carefully. If being around children upsets you, gracefully decline invitations to events where they are likely to be present. Know your limits and stick with them.

DO: Think of non-child centered holiday rituals. Take a vacation. Eat at a fancy restaurant.

DO: Continue to exercise moderately, eat healthy foods and get plenty of rest. You will feel better if you treat your body with care.

DO: Shop for the holidays online or from catalogs. You will avoid mall madness.

DO: Attend religious services at the time when there will be the least number of children. Attend a service on a university campus, which is more adult focused.

DO: Volunteer at a nursing home or homeless shelter. It may help others having difficulty coping and in turn may help you.

DO: Plan for how you will answer uninvited questions about when you’re going to have children. Remember, you are not required to tell them your entire “story!”

DO: Meet and talk with others who are experiencing similar feelings. Finding that you are not alone helps.

DO: Communicate with your partner to let him/her know of your feelings. If you are single, call a friend with whom you feel safe sharing your feelings.

Peggy Orlin, MFT

Sperm are clearly sensitive to environmental conditions. It is possible, through changes in lifestyle and activity, to improve sperm health. The studies available to evaluate environmental effects are unfortunately limited, but they offer insight into sperm sensitivity and ways to optimize their performance.

Temperature The scrotum where sperm are produced is 2 degrees lower than core body temperature. Raising the temperature by a few degrees results in a decline in sperm count and motility. Men suffering from cryoptorchidism, where the testicles are located above the scrotum, closer to central body temperatures, frequently suffer from low sperm counts. Infertile men tend to have a higher scrotal temperature⁽¹⁾, a characteristic that seems to be genetically determined⁽²⁾.

Common illnesses and every day activities can be sources of an increase in scrotal temperature. Acute fever associated with illness causes a significant decline in sperm quality⁽³⁾. In one study, total sperm count decreased within two weeks after a fever and required 79 days to return to normal. The DNA component of these sperm showed high levels of DNA fragmentation. Researchers in France installed temperature sensors to nine volunteers, and recorded scrotal temperatures while driving⁽⁴⁾. Scrotal temperature increased gradually over several hours, peaking 2.5 degrees higher at three hours. Another study showed that scrotal temperature was lowest while standing naked, and highest while clothed, seated, with legs crossed⁽⁵⁾. Higher scrotal temperatures have been associated with use of a laptop computer⁽⁶⁾. A group in Germany looked at scrotal temperatures with a variety of underwear⁽⁷⁾. As expected, tight underwear increased the temperature more than loose or no underwear. The effect was most pronounced while walking and less noticeable while sitting, since sitting temperature was somewhat elevated regardless of type of underwear worn.

The common sense approach is to avoid activities which can increase scrotal and testicular temperature, use loose-fitting underwear, and provide adequate ventilation to the scrotum. Exposure to hot tubs or saunas should be avoided. Take showers rather than baths, because heat conductance is lower when the testicles are not immersed in hot water. Sitting or driving for extended periods should be minimized.

Stress The effects of stress on sperm are complex. Under conditions of extreme stress, sperm counts decline. Analyses of prisoners awaiting sentencing have shown complete suppression of spermatogenesis on testicular biopsies⁽⁸⁾. A study of semen characteristics after the Slovenian war in 1991 showed a reduction in sperm count and motility, and a reduction in the proportion of male children born⁽⁹⁾. In 1995 a strong earthquake of magnitude 7.2 on the Richter scale occurred in Kobe, Japan killing 5,502 people. Sperm motility declined immediately, with low motility lasting for months⁽¹⁰⁾. The sperm of a man who lost his home and his father had still not recovered 10 months after the earthquake.

Stress associated with fertility therapy affects sperm and sexual function. Sperm parameters may decline in patients undergoing in vitro fertilization⁽¹¹⁾. Male fertility patients have a higher incidence of erectile dysfunction, ejaculatory disorders, loss of libido and a decrease in the frequency of intercourse⁽¹²⁾. One study of infertility patients showed an increase in burnout in male patients⁽¹³⁾.

Unfortunately, studies of the effect of stress reduction on sperm are rare,^(14)(15) so the treatment of stress has not been conclusively shown to improve sperm parameters⁽¹⁶⁾. In spite of the lack of clear data, stress reduction therapy is recommended for fertility patients and may reduce problems with sexual dysfunction.

Exercise The risk of developing male fertility problems appears to increase with the intensity of exercise. Intense exercise, such as endurance running, will lower levels of luteinizing hormone (LH) and testosterone.^(17)(18) Studies of semen characteristics have shown variable results. DeSouza⁽¹⁹⁾ developed the concept of a training volume threshold, in which running more than 100 km or 62.14 miles per week was associated with decreased levels of testosterone and sperm motility.

A detailed prospective study comparing competitive cyclists and triathletes with sedentary controls⁽²⁰⁾ was unable to show any suppressive effect of competitive exercise on FSH, LH, or testosterone levels. Although those with the highest levels of training had higher levels of circulating testosterone at baseline, these levels did not change with training. Competitive cyclists developed lower sperm motility during competition, however, motility values returned to normal following competition.

The best advice regarding exercise and sperm is moderation. While attempting conception, it is not advisable to undergo high intensity sports training. Good nutritional standards should be always be maintained when following an exercise program. An existing maintenance exercise program may be continued without concern for its effects on sperm.

Diet is a difficult topic to study in isolation, so fertility data is limited. A recent study of beef consumption showed that maternal consumption⁽²¹⁾ of beef resulted in lower sperm concentrations in sons. The proportion of men with low sperm counts was three times higher in the sons of women that consumed high levels of beef. Lifestyle, pesticide exposure, and xenobiotics (chemicals found in organisms that are foreign to them) were all considered potential factors. Heterocyclic amines (carcinogenic chemicals formed from the cooking of muscle meats), which are estrogenic, may also play a role⁽²²⁾.

Alcohol has long been associated with male reproductive dysfunction. Impotence, infertility, and male secondary sex characteristics are all affected by chronic alcohol use. Testosterone levels are lower, sperm production is reduced, and FSH and LH levels are affected⁽²³⁾. A study of chronic alcoholics demonstrated low levels of pituitary and testicular hormones, and significantly decreased sperm concentration and morphology⁽²⁴⁾. Sperm chromosomes are altered in men that consume alcohol⁽²⁵⁾.

Little data exists on the moderate consumption of alcohol. Data from the Ontario Farm Family Health Study did not show an adverse effect of alcohol consumption⁽²⁶⁾. In another study, alcohol or cigarette consumption did not alter sperm parameters, but when patients both smoked and drank alcohol a significant reduction in seminal volume, sperm concentration, percentage of motile spermatozoa, and a significant increase of the nonmotile viable gametes were detected⁽²⁷⁾.

Smoking tobacco affects sperm parameters, with reduced sperm counts, motility, and morphology reported in several studies⁽²⁸⁾. Whether these changes affect the male fertility remains uncertain. According to ASRM, “The effect of smoking on male fertility is … difficult to discern. The available data do not conclusively demonstrate that smoking decreases male fertility… Few studies have or can address the question, because of the confounding effects of partner smoking habits and fecundity. Although sperm concentrations, motility, and/or morphology are often reduced compared to results observed in non-smokers, they often remain within the normal range. Nevertheless, to the extent that the zona-free hamster egg penetration test reflects the ability of sperm to successfully fertilize a human oocyte, the available evidence suggests that smoking may have adverse effects on sperm function.”

Caffeine studies have revealed inconsistent effects on sperm, with at least one study showing no effect⁽²⁹⁾. Caffeine has been used as a sperm stimulant, increasing the motility prior to insemination. There does not appear to be any substantial adverse effect of caffeine on sperm.

Common Medications The list of medications with effects on sperm is long, and worthy of review. Noteworthy medications are the SSRI anti-depressants (Cipramil, Lustral, and Effexor were the reported medications), which were associated with near-azospermia in a case report⁽³⁰⁾. Ibuprofen (Advil, Nuprin) does not seem to cause adverse effects on sperm⁽³¹⁾.

Vaginal lubricants can interfere with sperm. FemGlide, Replens, and Astroglide lubricants demonstrated a significant decrease in motility, whereas Pre-Seed did not affect motility or DNA integrity⁽³²⁾.

Treatments for erectile dysfunction may have an effect on sperm motility. A significant increase in sperm progressive motility was observed after sildenafil (Viagra) administration as compared with baseline; in contrast, a significant decreased motility was observed after tadalafil (Cialis).

Antihypertensive drugs have numerous effects on sperm. Beta-blockers and diuretics have been associated with impotence. Calcium channel blockers (nifedipine, Procardia) have been associated with infertility⁽³³⁾. If you are on heart medications, review them with your physician.

Reports on the effects of marijuana use on sperm are conflicting. Early studies had poor controls, later studies showed reductions in testosterone and sperm quality⁽³⁴⁾ while other studies showed no effect on testosterone levels in chronic heavy smokers⁽³⁵⁾. A recent study revealed a direct effect of THC, the active ingredient in marijuana, on sperm motility and fertilization capacity⁽³⁶⁾. The conclusion of the study was that “the use of THC as a recreational drug may impair crucial sperm functions and adversely affect male fertility, especially in those who are already on the borderline of infertility.”

Conclusion Sperm are a biological substance, produced in a complex interplay of genetic predisposition, specific temperature and pH, and in association with specific cells and secretions. If the system is insulted, problems will often arise. The sheer numbers of sperm in an ejaculate provide a wide margin for maintaining fertility even after such insults occur, but repeated attacks on the reproductive system can ultimately result in male fertility problems.

Philip Chenette, MD

References:

1. Zorgniotti, A.W. and Sealfon, A.I. (1988) Measurement of intrascrotal temperature in normal and subfertile men. J. Reprod. Fertil., 82, 563–566.
2. Hjollund, N., Storgaard, L., et al. (2002) Correlation of scrotal temperature in twins: Brief Communication. Human Reproduction, 17(7):1837-1838.
3. Sergerue, D.E.S.S., et al., (2007) High risk of temporary alteration of semen parameters after recent acute febrile illness. Fertil Steril, In press.
4. Bujan L, et al. (2000) Increase in scrotal temperature in car drivers. Human Reprod 15, 1355–1357.
5. Mieusset, R. et al., (2007). Effect of posture and clothing on scrotal temperature in fertile men. J Androl. 28(1):170-175.
6. Sheynkin, Y., et al., (2006) Increase in scrotal temperature in laptop computer users. Human Reproduction. 20(2):452-455.
7. Jung, A., et al. (2005) Influence of the type of undertrousers and physical activity on scrotal temperature. Human Reproduction. 20(4):1022-1027.
8. Steve, H. (1952) Der ein Fluss de nerven System auf ban und Fatigkeit des Geschlechtorgane des Menschen. Theim, Stuttgart.
9. Zorn, B et al., (2002) Decline in sex ratio after 10-day war in Slovenia. Human Reproduction.17(12):3173-3177.
10. Fukuda, M, et al. (1996) Kobe earthquake and reduced sperm motility. Human reproduction. 11(6):1244-1246.
11. Clarke R.N., et al., (1999) Relationship between psychological stress and semen quality among in vitro fertilization patients. Human Reproduction. 14(3):753-758.
12. Lenzi, et al. (2003) Stress, sexual dysfunctions, and male infertility. J Endocrin Invest. 26(3 Suppl):72-6.
13. Sheiner, et al., (2002) Potential association between male infertility and occupational psychological stress. J Occup Environ Med. 44(12):1093-1099.
14. Pook, M, et al. (1999). Coping with infertility: distress and changes in sperm quality. Human Reproduction. 14(6):1487-1492.
15. Tuschen-Caffier B, Florin I, Krause W, Pook M. (1999) Cognitive-behavioural therapy for idiopathic infertile couples. Psychother Psychosom 68:15–21.
16. Campagne, D.M., (2006) Should fertilization treatment start with reducing stress? Human Reproduction. 21(7):1651-1658.
17. Wheeler, G. D., et al. (1991) Endurance training decreases serum testosterone levels in men without change in luteinizing hormone pulsatile release. J. Clin. Endocrinol. Metab. 72: 422–425.
18. Arce, J. C., et al. (1993) Subclinical alterations in hormone and semen profile in athletes. Fertil. Steril. 59: 398–404.
19. De Souza, M. J., et al. (1991) Gonadal hormones and semen quality in male runners. A volume threshold effect of endurance training. Int. J. Sports Med. 15: 383–391.
20. Lucia, A, et al. (1996) Reproductive function in male endurance athletes: sperm analysis and hormonal profile. J Applied Physiology. 81:2627-2636.
21. Swan SH et al (2007) Semen quality of fertile US males in relation to their mothers’ beef consumption during pregnancy. Human Reproduction. 22(6):1497-1502.
22. Cho E, Chen WY, Hunter DJ, et al. (2006) Red meat intake and risk of breast cancer among premenopausal women. Arch Intern Med 166:2253–9.
23. Emanuele, MA et al. (1998) Alcohol’s effects on male reproduction. Alcohol Health and Research World. 22:195-201.
24. Muthusami, KR et a;, (2005) Effect of chronic alcoholism on male fertility hormones and semen quality. Fertility and Sterility. 84(4):919-924.
25. Robbins, WA, et al. (2005) Effect of lifestyle exposures on sperm aneuploidy. Cytogenetic & Genome Research. 111(3-4):371-7.
26. Curtis KM, et al. (1997) Effects of cigarette smoking, caffeine consumption, and alcohol intake on fecundability. Am J Epidemiol. 146(1):32-41.
27. Martini, AC, et al. (2004) Effects of alcohol and cigarette consumption on human seminal quality. Fertility Sterility. 82(2):374-377.
28. Vine MF. (1996) Smoking and male reproduction: a review. Int J Androl.19:323–337.
29. Klonoff-Cohen, H, et al. (2002) A prospective study of the effects of female and male caffeine consumption on the reproductive endpoints of IVF and gamete intra-Fallopian transfer. Human Reproduction. 17(7):1746-1754.
30. Tanrikut C, Schlegel PN (2006) Antidepressant-associated changes in semen parameters. Fertil Steril. 86(3):S14.
31. Robinson, N, et al. (2005). Regular Use of Ibuprofen Does Not Affect Semen Analysis Parameters, Need for ICSI, or ART Clinical Pregnancy Rate. Fertility and Sterility (84): S14.
32. Agarwal A, et al., (2007) Effect of vaginal lubricants on sperm motility and chromatin integrity: a prospective comparative study. Fertil Steril. In press.
33. Hershlag A, et al. (1995) Pregnancy following discontinuation of a calcium channel blocker in the male partner. Human Reproduction. 10(3):599-606.
34. Kolodny RC, et al. (1974) Depression of plasma testosterone with acute administration. In: Braude MC, Szara S editor. The pharmacology of marijuana. New York: Raven Press; p. 217–225.
35. Mendelson JH, et al. (1974). Plasma testosterone levels before, during and after chronic marihuana smoking. N Engl J Med. 291:1051–1055.
36. Whan, LB, et al., (2006) Effects of delta-9-tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro. Fertil. Steril. 85(3):653-660.

In last month’s issue we introduced our readers to Peggy Orlin, MFT, Pacific Fertility Center’s in-house therapist. This month we interviewed her about the key psychological issues affecting individuals and couples experiencing infertility.

What is the most common reason why someone comes to see you at PFC? At Pacific Fertility Center everyone who uses a known or unknown egg or sperm donor or a gestational carrier is required to meet with me. This is mainly an educational session designed to help people think through and discuss the issues involved with using a third party to assist them in building a family. Each meeting is custom tailored to meet the patient’(s) particular needs.

	Use of a third party for reproduction and its impact on a relationship.
	Attachment to a non-genetically related child.
	Disclosure of third party reproduction to family, friends and the child.
	Choice of meeting or not meeting with the donor.
	Use of a family member or friend as the donor.
	Multiple pregnancy (twins or triplets) and its impact on your lives.
	Support services during and after treatment.

What are some of the other reasons people seek your help?
Some patients have had a failed cycle and are having trouble coping with the losses. Other patients have experienced a miscarriage. Both of these scenarios can leave patients feeling bereft and not sure how to move forward. During a session, I can help them understand the grieving process and we can discuss ways that they might ritualize their loss in order to move forward.

The stress of infertility diagnosis and treatment often brings them to me either at the center or in my private practice. It is important to understand that no two people will have exactly the same experience and that infertility can strongly impact those within a committed relationship. A recent diagnosis of infertility, as well as the stress and/or disappointments of treatment, can lead to feelings of isolation and depression. Additionally, people may experience grief over the loss of fertility choices. It is not uncommon that I am the first person, other than their partner, with whom they discuss their feelings about their infertility challenges.

There are those who are at a critical decision point and are seeking help thinking through their reproductive alternatives. This may include deciding whether or not to do one last IVF, move on to egg donation, select an egg donor or complete their family through adoption or childfree living. In the therapy sessions, we discuss and explore the pros and cons of a decision from the unique perspective of their life beliefs and situation.

Others may need help with developing positive coping mechanisms and stress reduction techniques such as setting aside time each day to discuss infertility with their partner, rather than allowing it to be a constant topic of conversation. We may also discuss how they can reduce their isolation possibly by talking with others who are having similar experiences. We may even explore how to include moderate exercise in their schedule to reduce symptoms of depression.

What is your advice to those who are uncertain whether or not they should see a therapist?
For patients at the clinic, one exploratory visit can be helpful. Their doctor can refer them to me for one free session during which we can discuss any concerns they may have and talk together about whether or not seeing a private therapist might be useful for them. They are not signing on for long-term therapy by talking with me. As with stress reduction techniques-it can’t hurt and it might help.

Could you discuss the Mind/Body@PFC Workshop and who might benefit from attending?
The jury is still out on the connection between stress and infertility. Recent studies indicate that there may be a stronger connection between depression and infertility than between anxiety and infertility. The Mind/Body classes not only teach people simple ways to relax, but the small group class gives them the experience of being in a safe environment with others who are all experiencing infertility and know just what it’s like to be going through infertility treatment. This group experience helps to reduce stress and may be helpful to ease mild depression. (Call 888-834-3095 to register or Click here for more information)

How does your private practice differ from your practice at Pacific Fertility Center?
Clients in my private practice tend to be those who are interested in more than one session. Some stay for a few sessions and some want longer-term therapy. Many are couples who are struggling with how differently they are approaching and/or moving toward resolution of their infertility journey. Sometimes clients are self-referred for infertility issues and then as we meet, they chose to move on to other issues in their relationship or their lives. Although I have a specialty with infertility patients, my private practice is with adults experiencing all types of distress.

Depression frequently accompanies infertility. When should someone seek a therapist?
The experience of symptoms of depression which last more than a couple of weeks is an important reason to set up an appointment with me or a therapist of your choosing. Remember, everyone will feel some of these symptoms, some of the time. They become a problem when the number and intensity of symptoms increase and/or don’t abate.

Symptoms of depression:
Feelings of emptiness or extreme sadness
Loss of interest and motivation to do regular activities
Increased level of anxiety
Decreased level of energy
Difficulty sleeping or sleeping more than usual
Difficulty concentrating
Abnormal weight loss or gain
Obsessive thinking about your infertility
Feelings of isolation from friends and family
Extreme and persistent feelings of anger
Persistent thoughts of death or suicidal thoughts or attempts
Persistent feelings of inadequacy, or worthlessness

What is the best way to make an appointment with you?
PFC patients phone the front desk at (415) 834-3000 and ask to set up an appointment. Those who prefer to see me outside PFC can make an appointment for a visit at either my San Francisco or Berkeley office by calling (510) 528-2750.

– Peggy Orlin, M.S., M.F.T.

Exercise and diet improvements are excellent enhancements to fertility therapy. There is evidence of a reduced risk of diabetes, high blood pressure, and pre-eclampsia in women who exercise in pregnancy. Some reports have identified a greater sense of well-being, shorter labor and fewer obstetric interventions in physically well-conditioned women. The standard recommendation by the Centers for Disease Control and Prevention, as well as the American College of Sports Medicine suggests that a minimum 30 minutes or more of moderate exercise per day, every day of the week, is ideal for pregnant women. The American Academy of Family Physicians and the American College of Obstetricians and Gynecologists (ACOG) endorse this 30 minutes per day recommendation.

In addition to physical benefits, gentle to moderate exercise is a healthy way to control the stress related to dealing with infertility diagnosis and treatment, but not all exercise is beneficial.

Level of Exercise
Everyone has a different level of exercise at which point it interferes with fertility. There is risk that the biological stress associated with exercise may induce ovulation problems and can, at times, increase the risks associated with fertility treatment. Maintaining or initiating a well balanced diet is important. This includes diverse nutrients (complex carbohydrates, balanced protein, low fat), a vitamin supplement and adequate hydration, especially during periods of exercise. Weight should be monitored: if weight loss occurs, intake should be increased; if weight gain occurs, intake should be evaluated and revised accordingly. Rapid weight gain or loss is not recommended.

Extreme exercise may affect fertility in both men and women. Serious athletes may have to add more calories to ward off fertility problems. Individual evaluation by a physician is recommended for those who are in a rigorous exercise program and concerned about their fertility.

If a woman has an established exercise program prior to treatment, that level of activity may be maintained and continued with some minor modifications and reasonable precautions.

If a woman has not begun an exercise program prior to treatment, a gentle start is advised such as walking or swimming 15 to 30 minutes, three days a week. A slow and steady increase in duration and frequency can be accomplished over a period of several weeks. A good guideline to follow is if it is difficult to carry on a conversation, slow down. For those starting a new program and can afford the luxury of a professional trainer, working with one who has expertise in exercise during pregnancy is a great way to begin.

Heavy exercise spurts followed by long periods of no activity is not recommended. Gentle to moderate, regular exercise is best.

Modifications to Exercise During Infertility Care
Generally, it is safe to assume that if an activity is uncomfortable, don’t do it, especially when considering discomfort in the region of the ovaries. Near the end of an IVF cycle and for a month after, avoid jostling tender ovaries and activities where even slight injury to the abdomen may occur. Ovaries are enlarged and may be uncomfortable when being jostled. Aside from causing discomfort, there is an increased risk of ovarian torsion, particularly after 5-7 days of gonadotropins. Bouncing exercises to avoid include vigorous step aerobics and running. Less traumatic, low impact exercises, such as walking, yoga, Pilates, swimming, are preferred.

A general rule of thumb is to aim for a target heart rate of 120-130 from stimulation day 8 to one week post transfer.

Contact sports or other activities that may increase the chance of bumping or hitting the abdomen or increase the risk of a fall such as horseback riding, vigorous racquet sports and downhill skiing should be avoided.

Avoid overheating especially during exercise; this includes hot tubs, hot yoga and exercising during very hot days.

Avoid conditions that limit oxygen availability especially during aerobic exercise; hiking up to a 6000 feet altitude is an acceptable limit.

Scuba diving is absolutely not recommended.

These are general guidelines, however, everyone’s level of comfort and physical condition is unique. It is always recommended patients discuss their exercise regimen with their physician.

– Philip Chenette, MD

As fertility care providers, a frequent question we are asked is “Does stress affect my chances of a successful outcome?” This is a difficult question to answer, because few substantial studies have been conducted. However, some viable data is starting to trickle in.

Researchers from the UC San Diego Dept. of Family and Preventive Medicine, working with a number of IVF centers, tried to assess the impact of patient worries on their IVF outcomes Konoff-Cohen et al, Fert Ster: Vol 81, No 4, 982-988). In this prospective study, 151 women completed questionnaires pre and post IVF or GIFT treatment regarding their concerns about medical aspects of their treatment (not achieving desired results, side effects, surgery, anesthesia, not enough information, pain, recovery) and financial aspects (missing work, finances). It is important to note that only the questionnaires completed pre-treatment provided data for this study, since not enough post-treatment questionnaires were returned.

Women who were concerned about the medical aspect of the procedures had 20% fewer eggs retrieved and 19% fewer fertilized, than women who were less inclined to worry about it. Women who were concerned about missing work had 30% fewer eggs fertilized. Those who were very concerned about the financial implications of their treatment cycle had a greater risk of not achieving a live birth. These results were adjusted for different variables that could also affect success rates such as age, race, smoking, type of infertility, previous treatment attempts, and prior live births. However, other important predictors of outcome were not adjusted for, such as FSH and antral follicle count.

While these findings may appear to show dramatic differences, it is important to note that these differences (20-30% fewer eggs, 19% fewer fertilized) clinically represented a decrease of only ONE fewer embryo transferred. The greatest decrease was seen in women > 35 yrs old, and those who had already done a treatment cycle.

This study represents an interesting look at the issues of personal concerns and IVF/GIFT outcomes, and calls for further studies to understand the potential physiological effects that may mediate these outcomes. Other related studies are also worth noting.

For instance, a well-done study (Domar), which we described in the November/December 2003 issue of Fertility Flash, has shown that women participating in support groups while in IVF treatment seem to have increased pregnancy rates. A recently published study (Facchinetti) has looked at changes in physiological markers (heart rate, blood pressure, cortisol levels) in women undergoing IVF treatment and participating in support groups, showing evidence of physiological changes for those in support groups. These physiological changes are consistent with those seem in lower stress situations.

These collective studies suggest that one can best prepare for IVF by being as informed as possible about expectations of one’s treatment cycle (treatment procedures and financial impact). It may also be helpful to consider joining a support group. Fertility clinics can help patients by trying to alleviate patient’s concerns and making the IVF experience as smooth as possible.

Following Halloween, the holiday season suddenly looms. Excited children, crowded stores, decorations, and holiday parties are all set to descend on us. Yet because the winter holidays tend to celebrate families and children, these usually joyous occasions can bring up painful feelings when you are struggling to create and celebrate with a family of your own. In order to feel as good as possible during the holidays, you will need to develop some good holiday coping skills. Coping is “developing the ability to manage in a difficult situation.” Here are a few suggestions. Use whichever of these suggestions seems helpful to you. Do what feels right for you.

DO: Give up any and all feelings of guilt for how you are feeling. There is no right or wrong way to experience infertility. Your feelings may run the gamut from indifference to intense anger and despair and everywhere in between.
DO: Reach out to childfree friends. Their parties will be adult-focused.
DO: Choose the gatherings you attend carefully. If you are upset by being around children or babies gracefully decline invitations to events where they are likely to be present. Know your limits and stick with them.
DO: Think of non-child centered holiday rituals. Take a vacation. Eat at a fancy restaurant.
DO: Continue to get moderate amounts of exercise. Eat healthy and get plenty of rest. You will feel better if you treat your body with care.
DO: Shop for the holidays online or from catalogs. You will avoid mall madness.
DO: Attend religious services at the time when there will be the least number of children. Or attend on a university campus, as those services tend to be more adult focused.
DO: Volunteer at a nursing home or homeless shelter. It may help to help others having a difficult time at the holidays.
DO: Plan for how you will answer uninvited questions about when you’re going to have children. Remember, you are not required to tell them your entire “story!”
DO: Meet and talk with others who are experiencing similar feelings. Finding that you are not alone helps. DO: Communicate with your partner to let him/her know of your feelings. If you are single, call a friend with whom you feel safe to share your feelings.

Stress reduction through mindful well being… while this may sound like a new age mantra, the medical community is growing in consensus about a mind/body connection that can positively impact a patient’s health. No other physician has probed the mind/body infertility correlation deeper than Alice D. Domar, Ph.D., who has written extensively on health and stress, conducted research and designed a comprehensive workshop series. Included in these mind/body and mindfulness health and wellness programs are relaxation techniques involving controlled breathing and posture awareness; yoga, meditation, journaling, neuro-linguistic programming, and joining a support network. Dr. Domar’s techniques are designed to help women treat their own stress responses so their bodies might have a higher chance of conceiving. Pacific Fertility Center’s team has examined the scientific, medical and anecdotal information surrounding the topic of stress and infertility. And because various relaxation inducing/stress reducing techniques are likely to have an overall positive impact on a patients’ general health, PFC is offering classes modeled around Dr. Domar’s mind/body practice (see Mind/Body@PFC) Indeed, infertility clinics all over the country are offering similar programs despite the lack of scientific consensus about how stress affects fertility. Skeptics point out that millions of people under extremely stressful circumstances, even kidnap and rape victims, regularly get pregnant. But some facts are clear: Ongoing chronic stress can affect menstrual function; change hormone levels; alter blood sugar; increase heart rate and change a person’s immune response. Mind/body therapies are frequently initiated for groups with serious medical conditions, from lupus to multiple sclerosis to major heart disease. It is only natural that the more serious an illness, the more anxiety it can induce in a patient, thus potentially bringing on accelerated and aggravated symptoms. This vicious stress/body cycle, when broken through stress reduction techniques, can provide overall improvement in health. Dr. Domar’s initiated one of the few controlled studies funded by the National Institute of Mental Health on this topic. Results of the research showed an improvement in pregnancy rates using either relaxation techniques or though the psychological support of joining a group. With so much growing attention into the mind/body stress reduction methodologies, there is bound to be a greater body of critical scientific knowledge gathered. Meanwhile, take a deep breath and consider your own stress response strategy.

– Carolyn Givens, M.D. and Isabelle Ryan, M.D. contributed to this article