A Four-Step Protocol for Improving the Effects of Clomiphene in Patients With Ovulatory Dysfunction Infertility
By Bob Flaws, LAc, FNAAOM (USA), FRCHM (UK)
Clomiphene is a selective estro-gen-receptor modulator (SERM), which is mainly used in the treatment of female infertility due to anovulation, as in the case of polycystic ovarian syndrome.
This drug also is commonly used before patients undergo an assisted reproductive technology (ART) treatment, such as in-vitro fertilization (IVF), to encourage the production of several eggs.
Clomiphene usually is taken in pill form for one five-day cycle a month. It inhibits the action of estrogen on the gonadotrope cells in the anterior pituitary gland. In response to low estrogen levels, follicle-stimulating hormone (FSH) release is increased, thus leading to a higher rate of ovulation. However, it can lead to multiple ovulations and increase the chance of twins. Side effects include mild swelling of the ovaries, stomach pain, breast tenderness, insomnia, nausea/vomiting, blurred vision, headaches, fatigue, irritability, depression, weight gain and, in rarer cases, ovarian cysts. There also may be an increased risk of ovarian cancer. However, Chinese medicine can prevent these side effects, as well as improve cervical mucus and the thickness of the endometrial lining when used in tandem with clomiphene. For instance, in the Zhejiang Journal of Chinese Medicine (2007;7:405), Shi Jian-Jun, et al., published an article titled "Clinical Observations on A Four-Step Method for Regulating Menstruation on Improving the Adverse Effects After Clomiphene Induction of Ovulation." A summary of this article is presented below.
Cohort Description: A total of 110 patients diagnosed with female infertility were enrolled in this two-wing comparison study. These 110 were then randomly divided into two groups - a treatment group of 60 and a comparison group of 50. Within the treatment group, the median age in these patients was 29.17 ± 3.50 years, and the median duration of infertility was 4.23 ± 1.81 years. Forty-four cases suffered from primary-onset infertility and 16 cases from secondary infertility. In the comparison group, the median age was 29.60 ± 3.23 years and the median duration of infertility was 4.10 ± 1.75 years. Thirty-eight of these cases suffered from primary onset infertility and 12 cases from secondary onset infertility. Therefore, for the purposes of this study, these two groups were deemed statistically comparable in terms of age, disease duration and type of infertility.
Treatment Method: All members of the treatment group received the following four-step protocol for the regulation of menstruation with Chinese medicinals.
Menstrual period: In order to warm the menses and scatter cold, quicken the blood and transform stasis, Shao Fu Zhu Yu Tang (Lesser Abdomen Dispel Stasis decoction) with additions and subtractions was administered:
Dang gui (Radix angelicae sinensis) Pu huang (Pollen typhae), uncooked Wu ling zhi (Feces trogopterori), stir-fried Yan hu suo (Rhizoma corydalis), 10g ea Chi shao (Radix rubra paeoniae) Chuan xiong (Rhizoma chuanxiong) Gan cao (Radix glycyrrhizae), 9g ea Xiao hui xiang (Fructus foeniculi), 12g Ru xiang (Olibanum), stir-fried Mo yao (Myrrha), 6g ea, stir-fried Rou gui (Cortex cinnamomi), 5g
Post-menstrual period: In order to increase essence and boost the kidneys, nourish the blood and regulate menstruation, Yi Shen Tiao Xue Tang (Boost the Kidneys and Regulate Menstruation decoction) with additions and subtractions was administered:
Shu di (Radix rehmanniae), cooked Shan zhu yu (Fructus corni) Nu zhen zi (Fructus ligustri lucidi) Tu si zi (Semen cuscutae) Rou cong rong (Herba cistanchis), 12g ea Dang gui (Radix angelicae sinensis) Shan yao (Radix dioscoreae), stir-fried Xiang fu (Rhizoma cyperi), stir-fried Gan cao (Radix glycyrrhizae), 10g ea
Mid-cycle: In order to boost the kidneys and course the liver, quicken the blood and free the flow of the network vessels, Shu Gan Huo Xue Tang (Soothe the Liver and Quicken the Blood decoction) with additions and subtractions was administered:
Bai shao (Radix alba paeoniae) Mai ya (Fructus germinatus hordei), uncooked Shi xian chuan (Squama manitis) Lu jiao pian (Cornu cervi), 12g ea Dang gui (Radix angelicae sinensis) Dan shen (Radix salviae miltiorrhizae), 10g ea Chai hu (Radix bupleuri) Gui zhi (Ramulus cinnamomi) Gan cao (Radix glycyrrhizae), 9g ea Shui zhi (Hirudo), 6g
Premenstruum: In order to warm yang and boost the kidneys, Wen Yang Yi Shen Tang (Warm Yang and Boost the Kidneys decoction) with additions and subtractions was administered:
Tu si zi (Semen cuscutae) Zi shi ying (Flouritum) Xian ling pi (Herba epimedii) She chuang zi (Semen cnidii) Shu di (cooked Radix rehmanniae) Sang ji sheng (Herba taxilli), 12g eaXiang fu (Rhizoma cyperi) Gan cao (Radix glycyrrhizae), 9g ea Dang gui (Radix angelicae sinensis), 10g Ba ji tan (Radix morindae officinalis), 15g
When it says "with additions and subtractions" above, it means that these base formulas were modified according to each patient's presenting patterns. Both groups also were administered 50-100 mg of clomiphene per day, beginning on day five and continuing for five days. One month equaled one course of treatment and results were analyzed after three such courses.
Study outcomes: In the treatment group, there were a total of 152 menstrual cycles with 127 ovulations (83.6 percent). In addition, there was a conception rate of 41.7 percent. In the comparison group, there were 137 menstrual cycles with 102 ovulations (74.5 percent) and only a 22 percent conception rate. Thus there was no marked difference in the total ovulatory rate between these two groups but there was a significant difference in the rate of conception. In addition, Insler scores were tabulated for all members of both groups before and after treatment. The Insler score is a way of scoring the quality of vaginal mucus at ovulation. A score (out of 12) for the quality of cervical mucus, gauged by scoring each of the following from zero to 3. 1) The cervix should be open and the volume of mucus should be good; 2) Although every woman will be different for both these parameters, they will be consistent in one woman from ovulation to ovulation; 3) The mucus should be clear, watery and stretchy (Spinnbarkheit); 4) The mucus should produce a complete "ferning" pattern when it is allowed to dry on a microscope slide. The first two criteria vary at ovulation in different women (so anything above a score of 9 or 10 can be normal), but the same woman should achieve the same cervical score from one ovulation to the next. The following table shows the median Insler scores for the two groups. This chart also shows the mean thickness of the endometrium in both groups before and after treatment.
As this table shows, the mean Insler score in the group which received both the Chinese medicinals and clomiphene was much higher after treatment than that of the group which only received the clomiphene. In addition, there also was a significantly thicker endometrium in the treatment group after treatment than in the comparison group. And finally, after treatment, the menstrual cycle was normal in 47 patients (78.3 percent) in the treatment group compared to only 30 cases (60 percent) in the comparison group.
Discussion: According to the authors of this study, ovulatory dysfunction is a main cause of female infertility and clomiphene citrate is commonly used to induce ovulation in such women. However, the conception rate with this drug does not correspond to what one would like. Unfortunately, using the four-step method of regulating menstruation alone does not achieve as high a rate of ovulation as does clomiphene. Therefore, the authors of this study decided to combine the use of clomiphene with this four-step menstruation-regulating method.
3.37 ± 2.06
0.62 ± 0.20
8.14 ± 2.12
0.85 ± 0.17
3.28 ± 2.00
0.63 ± 0.26
6.53 ± 2.64
0.69 ± 0.24
During menstruation, the sea of blood is full and exuberant and is the time for its discharge. During that time, the use of blood-quickening and stasis-transforming medicinals benefits corpus luteum by promoting the complete shedding of the endometrial lining. After menstruation, the blood is consumed and damaged, and the sea of blood is empty and vacuous. Now, medicinals for increasing the essence and boosting the kidneys not only increases serum estrogen levels but also improves the cervical mucus, thus making it easier for the sperm to penetrate it. It also promotes the growth of the endometrial lining. Mid-cycle, yin transforms into yang. Therefore, boosting the kidneys and coursing the liver, quickening the blood and freeing the flow of the network vessels can promote the maturation and the expulsion of the ovum. It also insures a healthy environment for the zygote to implant in the endometrium. During the premenstruum, kidney yang qi gradually becomes effulgent, and eventually, double yang transforms into yin. At this time, the use of medicinals to warm and supplement kidney yang along with kidney yin-supplementing medicinals, further promotes the proper environment for the zygote to implant and develop. Not only does the combination of clomiphene with this four-step method improve the conception rate, it also has no adverse side effects. Therefore, the authors believe this method achieves relatively good therapeutic effects.
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