- INTRODUCTION TO ARC FERTILITY PROGRAM
- FERTILITY OPTIONS
- ADVANTAGES OF PACKAGES
- FINANCIAL SERVICES
- ARC PHARMACY PLAN
- HOW TO GET STARTED
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OBJECTIVES FOR MANAGING INFERTILITY Overall objectives for managing infertility include making an accurate diagnosis and then utilizing guidelines for medical treatment, surgical treatment, or use of ART. In addition, overall disease state management should be implemented from the beginning of treatment and conditions under which discontinuation of therapy will occur should be identified. Efforts to help the couple understand the course of diagnosis and treatment, their options, endpoints in treatment, and eventual resolution of their infertility should be established at the time of initial diagnosis. Cost-effective infertility management depends on an organized plan of diagnosis and treatment from the time of initial presentation. This includes the use of simpler, cheaper tests first, and the establishment of a correct diagnosis followed by simultaneous treatment of the male and female utilizing effective therapy. Cost-effectiveness increases with shorter duration of therapy and faster referral for unsuccessful couples. Patient satisfaction, which includes involvement in the decision-making process, also improves cost-effectiveness. Finally, resolution of the couples' infertility, either through the birth of their own biologic child or through other options, needs to be achieved as quickly and cheaply as possible. Initial testing of infertile couples should be carried out in the most cost-effective manner possible. Depending on the results of initial tests secondary infertility tests can be performed. The role of these tests is to obtain a comprehensive evaluation of the couple based on their clinical history and physical examination. Each couple potentially has six options. These are no treatment, standard medical and surgical treatment, assisted reproductive technologies, use of donor gametes or gestational carrier or surrogate, adoption, and child-free living. The decision as to which of these options to pursue and in which order depends upon a cost-benefit analysis of the couple's unique situation. The benefit of any management approach is equal to the product of the value the couple places on the outcomes of each of the above options, multiplied by the probability that the event will occur if management is directed towards that choice. The value is determined solely by the couple based on a complete understanding of the different options. The probability of success is dependent upon the clinician's evaluation of the clinical history and physical examination and tests. Once the options have been prioritized they must be considered in view of the costs of treatment. These include four types of costs. The first is the financial cost. This includes the actual cost, determination of how much money the couple has, how much they want to spend, and what proportion will be covered by their insurance. The second cost is time and will reflect the duration of infertility, the patient's age, and the woman's ovarian reserve. A third cost are health risks associated with infertility treatment. Mortality is very low relative to the risk of being pregnant, but morbidity needs to be considered, in particular the potential risk of ovarian cancer, and especially the risk of multiple pregnancies with attendant complications for babies, mother, family, and society. Finally, the emotional and psychological costs associated with infertility treatment need to be considered for each couple. Only by a comprehensive overview of each couple's situation can the best approach be ascertained. COST-EFFECTIVE DECISION-MAKING It is important for all physicians to recognize that counselling patients in decision-making is a complex and subtle science and art which is frequently done poorly. Physicians are biased in their counselling by the poor quality of information available in general, and further limited by their own knowledge base. Many do not recognize that different people make decisions in different ways, some intuitively, some based on experience, and others based on a straightforward analysis of the facts. It is clear that many people derive conclusions based on small numbers which are not representative of the expected outcome in larger populations. In addition, it is very easy to attribute causality to certain events and outcomes, when in fact no causality has occurred. Our decisions are also strongly influenced by outcomes we see in a few of our own patients, yet these outcomes may not reflect the generally expected outcome from a certain series of events or treatments. Some people make irrational choices, but it may be difficult to separate these from just unusual choices. Both physicians and their patients are capable of making irrational choices. These include a bias towards securing benefits and avoiding harm in the present and near future as opposed to the more distant future. For low probability events many patients also feel "it won't happen to me" and are prepared to discount risks entirely. Some patients have a fear or anxiety about an operation and/or its sequelae that greatly exceeds the actual risks or pain. Distinguishing between a reasonable and unreasonable exaggeration of concern is often difficult. Sometimes patients have values or beliefs that do not make sense to many others, but are important to them. It is reasonable to honor these beliefs as long as doing os does not force the physician to practice unethical or unacceptable medicine. Most importantly, the way choices are formulated or "framed" by surgeons can cause patients to make irrational decisions. Patients tend to focus more on losses and risks than gains when evaluating surgical options, and their decision can be biased significantly whether they are told there is an 80% chance of improved outcome or a 1% chance of death. Usually the best approach is to present the available choices in alternative ways to allow patients to look at the various options from different perspectives. This minimizes "framing" effects. Decision-making in infertility is becoming increasingly complex because of ethical issues. The first question which must be asked is, "What are the indications for treatment?". In couples in whom the prognosis is good without any intervention at all, the surgeon must be careful not to utilize unnecessary treatment. It is clear that a substantial number of couples will conceive without treatment. Patient preferences can also create ethical dilemmas. Especially in infertility the media provides extensive coverage of infertility and usually information associated with high technology, high cost therapy. Many physicians feel that increased public awareness associated with an erosion in the authority of the medical profession in general has resulted in increased expectations about what medicine can offer. This may be especially true for older patients. Physicians are under no obligation to render useless health care regardless of its safety just because a patient requests it. Where there are interventions which can only be evaluated subjectively, established community standards should be utilized with an explanation of the treatment rationale and other alternatives given to the patient. In situations in which there is a finite potential for both benefit and harm, the patient's weighing of the possible approaches and outcomes should take precedence over those of the physician. Second opinions should be offered when necessary so that the patients could make the most informed decisions. It is important to establish the religious, moral, and ethical values of the couple and the physician early in any decision-making process. Should there be significant variance or nonacceptance of all views, then alternative sources of health care should be identified for the benefit of all involved. Ethical dilemmas exist when options for care conflict with the patient's autonomy, quality of life, or social justice. The most important principle is to avoid harm in making decisions. MANAGEMENT OF PSYCHOLOGICAL ISSUES Physicians are responsible for consultation, medical decision-making, and provision of sophisticated technical, laboratory, and operative interventions to their patients. They must also be able to provide these services within the context of the psychological status of the patient and his/her partner. Therefore, they must be able to recognize and appreciate this context and be able to utilize additional nursing and mental health resources with necessary. Part of the physician's role in counseling is to provide accurate and comprehensive facts to the couple to help them decide how to manage their infertility. Interventions that are generally worth considering include:
Couples should be able to proceed at their own pace, within medically appropriate guidelines. Physicians should freely offer second opinions if patients appear to desire one or are excessively questioning or concerned about the planned management. Physicians should counsel patients that they may have problems coping with some aspects of their investigation and treatment because of the physical discomfort or emotional stress. Physicians need to counsel couples about problems associated with conceiving, that is the increased rate of pregnancy loss and other obstetrical and neonatal complications associated with infertile patients. The couples also need to be informed about the dramatic changes in lifestyle which occur with parenting, and the need not to have unrealistic expectations for themselves or their child. Sometimes, the physician just needs to be "there", to listen, to comfort, and "to take on sadness from time to time", become frustrated and tired, but not lose patience. THE FUTURE There are trends developing which will prevent infertility from becoming a bottomless pit. These include integrated networks and prepaid medical groups and decentralized care, meaning office and outpatient care. There is a massive consolidation of health plans and buyers occurring, and the directing of patients to certain health plan providers who follow protocols of the managed care organizations. In addition, regionalization of high technology services will enable increased control of these costs. New information systems will enable management of clinical care in real time settings using algorithms which can be evaluated on an ongoing basis by the same clinical management information systems. Currently, outcomes are measured through utilization review, physician profiling, clinical practice guidelines, disease management programs, outcomes management, and outcomes research. It can be expected that the effort, technology, and involvement of outcome measurement in medicine will increase dramatically during the next decade. It is likely that we will see capitation or global budgets for at least some infertility care with increases based on a consumer price index. An increasing focus on early diagnosis and preventive care will also help to control costs. Most importantly, it is clear that physicians will be held accountable for quality of care and outcomes on a global basis. Many of the coming changes will also produce profound ethical dilemmas for physicians' forced to function in systems in which the patient's immediate need is not allowed to be their only concern. CONCLUSION The cost and effectiveness of infertility treatment are the primary forces driving clinical care today. It is imperative that physicians educate themselves about this seemingly simple, yet actually very complicated, aspect of clinical medicine. The provision of cost-effective care requires an understanding of definitions and statistics, an ability to initially evaluate the medical literature, knowledge of treatment outcomes in multitudinous situations, factors affecting treatment outcomes, actual costs of providing care in their own setting, comprehension of biases in decision-making, an ability to counsel patients in difficult emotional situations, the ability to coordinate complex options using sound clinical judgment, an understanding of the role of practice parameters and the complexities of managed care, and an ability to find their way through ethical mine fields. It will not be easy, but we must become involved, and move forward so that we can continue to be our patient's advocate and capable of providing cost-effective, optional and ethical patient care.
TABLE I WHEN TO PROCEED TO ARTƯ The decision to proceed to ART can be difficult for many couples and physicians, but studies completed in the past few years do help in making this decision. The major factor affecting the decision to proceed to ART is the diagnosis, but other factors can also be important. Absolute indications for IVF include the following:
Other factors are relative indications for ART procedures. These include:
8. Moderately limited sperm availability following cryopreservation for cancer. 9. Failure to conceive following ovarian stimulation and intrauterine insemination.
Some factors which cause infertility cannot be treated by ART. Some of these include the following:
Other issues that need to be considered before proceeding to ART include the management of hydrosalpinges. While some controversy still exists, there are reasonable data to support salpingectomy for large hydrosalpinges prior to IVF because the live birth rate is reduced from approximately 25% to 15% per cycle in the presence of large hydrosalpinges. However, some more recent studies have suggested that salpingectomy might compromise ovarian function. It would be preferable to have some prospective randomized trials to answer definitively this question, but in the absence of such data, it is important to review the advantages and disadvantages of salpingectomy prior to IVF. Another surgical decision which now must be considered is whether or not asymptomatic intrauterine myomas should be resected prior to IVF. One paper has reported pregnancy rates of 16% per cycle with intramural myomas and 10% with submucosal myomas not distorting the uterine cavity compared to 30% or more in patients with no myomas or subserosal myomas. It has been my practice to remove myomas before ART when the myoma distorted the uterine cavity, was larger that 8 centimeters, consisted of 3 or more myomas larger than 5 centimeters or was associated with menorrhagia. These new data must now also be considered. Further studies confirming this initial finding would be helpful in elucidating how often pre-ART myomectomy should be performed. WHAT ART PROCEDURE?The couple undergoing ART have a number of choices regarding procedures available to them. Sometimes the decision is easy as to which procedures should be chosen and sometimes the choice is quite unclear and complicated. IVF vs GIFT vs ZIFT One of the first choices is whether to perform IVF or GIFT or ZIFT. For many years, GIFT success rates have been higher than IVF success rates in SART statistics and other reported studies. This seems to be particularly true for women who are in their forties, and numerous studies have confirmed these results. Supporters of GIFT have suggested that the intrafallopian environment is superior to that in the laboratory and that the timing of embryo implantation is superior in GIFT, leading to higher success rates. Many others have argued that the difference in results is due to patient population differences, with IVF patients having more severe pelvic disease, especially endometriosis, and male factor which are confounding variables leading to lower pregnancy rates. These differences in success rates seem to be narrowing. The 1996 SART success rates show that live birth rate per retrieval for IVF is 25.9%, for GIFT is 28.7% and for ZIFT is 30.3%. The general consensus is that IVF must be fairly equivalent because about 92% of the initial oocyte retrievals are for IVF and 6% for GIFT. In our program patients undergo GIFT when they have other indications for a laparoscopy, have economic incentives compared to IVF and tend to be older. ZIFT is performed for about 2% of initial cycles and pregnancy rates have been shown consistently not to be different that those of GIFT. Intracytoplasmic Sperm Injection vs Donor Insemination A second procedure which needs to be considered is intracytoplasmic sperm injection (ICSI). This technique has revolutionized treatment for male factor infertility. When male factor is present ICSI should be discussed with the couple prior to IVF. The decision to utilize ICSI will usually be made by the gamete biologist at the time of the IVF retrieval. Different laboratories use different criteria, but usually ICSI will be considered if the male produces fewer than 100,000 total motile sperm or morphology by strict morphology is less that 5% normal. ICSI has been very successful with 1996 results showing a live birth rate (LBR) per retrieval of 27.8% for ICSI patients and 25.6% for non-ICSI patients. ICSI was used in 31.5% of IVF cycles in 1996. In cases in which ICSI is not able to be successful or the couple prefer not to utilize ICSI, donor sperm can be an alternative. Couples need to be fully informed about this option and its potential advantages, especially before the male undergoes any surgical procedures for sperm retrieval. In our program, counseling with a mental health professional is mandatory before donor sperm can be used. This is simply to ensure that the couple have considered and resolved all the potential issues before proceeding. Some recent concerns have been raised about ICSI, including the possibility of an increased rate of congenital anomalies in some populations of men treated with ICSI. Therefore, patients who have ICSI in our program are counseled to undergo amniocentesis, even though most large studies show no increase in the overall incidence of congenital anomalies for patients undergoing ICSI. Assisted Hatching vs No Assisted Hatching Another laboratory procedure to be considered is assisted hatching. The literature data are mixed on the efficacy of this technique. Two papers confirm its effectiveness while others show no difference in pregnancy rates. The SART Practice Committee has found this procedure not yet to have proven clinical effectiveness. Most clinicians select patients who are older than 38, have a thickened zona pellucida or have prior failed IVF cycles. The potential benefit of the procedure needs to be balanced against the cost and potential damage to the embryo undergoing hatching. COMMITTEE OPINIONThe Role of Assisted Hatching in IVF: A Review of the LiteratureIn vivo hatching of the blastocyst is a critical component of the physiologic events culminating in implantation. Conversely, the failure to hatch (whether due to intrinsic abnormalities of the blastocyst, zona pellucida or endometrium) may be one of the many factors limiting human reproductive efficiency. The clinical application of assisted hatching has been proposed as one approach toward the enhancement of implantation and pregnancy rates following in vitro fertilization (IVF). In 1989, Cohen and associates reported an increased implantation rate following mechanical opening (partial zona dissection-PZD) of the zonae pellucida in embryos resulting from IVF. These investigators postulated that the opening of the zona might enhance the subsequent hatching process. Cohen et al subsequently published a randomized, prospective trial of selected assisted hatching 72 hours post-retrieval (zona drilling with acidified Tyrode’s medium), which suggested an improvement in implantation rates when the procedure was selectively applied to embryos with a "poor prognosis" (based on zona thickness, blastomere number, fragmentation rates, maternal age, etc.). Since these early reports, many ART programs have incorporated the use of assisted hatching in an effort to improve clinical outcomes for their patients. The assisted hatching procedure is generally performed on day 3, and entails the creation of a gap in the zona either by drilling with acidified Tyrode’s medium (Hurst, Lanzendorf), PZD with a glass microneedle (Hellebaut), laser photoablation (Obruca) or use of a piezomicromanipulator (Nakayama). The assisted hatching procedure has been implicated in an increased rate of monozygotic twinning and possibly conjoined twins (Alikani, Skupski, Herschlag). Success rates following the use of assisted hatching in different ART programs have varied considerably. It is, however, difficult to compare reports from different clinics due to differences in their patient populations, experience, technique of hatching and study design. Table 1 summarizes the reports of six programs from 1996 to the present. These studies utilized three different hatching techniques, all of which had at least one report of a significant improvement in clinical pregnancy and implantation rates following its use. Three of these studies demonstrated no benefit with the use of assisted hatching (Hellebaut, Hurst, Lanzendorf). All were prospective, randomized trials. Of note, all of these three negative studies were performed in the context of a broad patient population (i.e. all patients, all good prognosis patients, and offered to all patients 36 years and older). Three additional prospective, randomized studies were performed on a specific patient population, namely those with multiple IVF failures (Chao, Magli, Nakayama). These studies reported a significant increase in clinical pregnancy and implantation rates following assisted hatching. Review of these reports suggests that assisted hatching may be clinically useful, and that individual ART programs should evaluate their own patient populations in order to determine which subgroups may benefit from the procedure. The routine or universal performance of assisted hatching in the treatment of all IVF patients appears, at this point, to be unwarranted. References Alikani M, Noyes N, Cohen J, Rosenwaks Z (1994) Monozygotic twinning in the human is associated with the zona pellucida. Hum Reprod 9:1318-21. Chao KH, Chen SU, Chen HF, Wu MY, Yang YS, Ho HN (1997) Assisted hatching increases the implantation and pregnancy rate of in vitro fertilization-embryo transfer, but not that of IVF-tubal embryo transfer in patients with repeated IVF failures. Fertil Steril 67:904-8. Cohen J, Alikani M, Trowbridge J et al (1992) Implantation enhancement by selective assisted hatching using zona drilling of human embryos with poor prognosis. Hum Reprod 7:685. Cohen J, Inge KL, Suzmann M (1989) Video-cinematography of fresh and cryopreserved embryos: a retrospective analysis of embryonic morphology and implantation. Fertil Steril 51:820-7. Hellebaut S, De Sutter P, Dozortsev D, Onghena A, Qian C, Dhont M (1996) Does assisted hatching improve implantation rates after in vitro fertilization or intracytoplasmic sperm injection in all patients? A prospective randomized study. J. Assist Reprod Genetics 13:19-22. Herschlag A, Paine G, Cooper W, Scholl GM, Rawlinson K, Kvapil G, (1999) Monozygotic twinning associated with mechanical assisted hatching. Fertil Steril 71:144-6. Hurst BS, Tucker KE, Awoniyi A, Schlaff WD (1998) Assisted hatching does not enhance IVF success in good-prognosis patients. J Assist Reprod Genetics 15:62-4. Lazendorf SE, Nehchiri F, Mayer JF, Oehninger S, Muasher SJ (1998) A prospective, randomized, double-blind study for the evaluation of assisted hatching in patients with advanced maternal age. Hum Reprod 13:409-13. Magli MC, Gianaroli L, Ferraretti AP, Fortini D, Aicardi G, Montanaro N (1998) Rescue of implantation potential in embryos with poor prognosis by assisted zona hatching. Hum Reprod 13:1331-5. Nakayama T, Fujiwara H, Yamada S, Tastumi K, Honda T, Fujii S (1999) Clinical application of a new assisted hatching method using a piezomicromanipulator for morphologically low-quality embryos in poor-prognosis infertile patients. Fertil Steril 71:1014-8. Obruca A, Strohmer H, Sakkas D (1994) Use of lasers in assisted fertilization and hatching. Hum Reprod 9:1723-6. Skupski DW, Streltzoff J, Hutson JM (1995) Early diagnosis of conjoined twins in triplet pregnancy after in vitro fertilization and assisted hatching. J Ultrasound Med 14:611-5. Owen Kidder Davis, M. D./To Board for Review 3/20/00cf Table 1. Prospective randomized assisted hatching studies performed from 1996 to 1999.
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