PREGNANCY RATES MIGLIORATI CON L’APPORTO DI FITOTERAPIA A BASE DI MACA POLARIZZATA: I RISULTATI DI UNO STUDIO PROSPETTICO RANDOMIZZATO IN UN PROGRAMMA DI INSEMINAZIONI INTRATUBARICHE
G. MENALDO, S. SERRANO
Istituto di Medicina della riproduzione e Ginecologia psicosomatica ( S. Carlo – Ipog ) di Torino
Centro di Ricerche in Bioclimatologia medica – Biotecnologie – Medicina naturale
Università degli Studi di Milano
L’obiettivo di questo studio prospettico randomizzato è stato quello di valutare se la fitoterapia andina a base di Maca polarizzata (Lepidium Meyenii Walp ), conosciuta sin dai tempi degli Inca come “pianta della fertilità“, fosse in grado, associata con bassi dosaggi di FSH ricombinante, di aumentare i tassi di gravidanza ( pregnancy rates ) in un programma di inseminazioni intrauterine (ITI ).
A questo scopo sono stati confrontati due gruppi omogenei di n° 63 coppie cadauno scelti a random con problemi di infertilità da oltre 3 anni.
Il gruppo A di controllo non sottoposto a fitoterapia, ha effettuato n° 110 cicli di inseminazione intratubarica dopo una stimolazione dell’ovulazione unicamente con FSH ricombinante a basso dosaggio sino al giorno precedente la somministrazione di 7000 IU di HCG.
Il gruppo B, sottoposto a fitoterapia sia nella componente maschile che femminile, ha effettuato n° 132 cicli di inseminazione intratubarica dopo stimolazione dell’ovulazione con maca polarizzata ( LMWP: 3 cps. Al dì dal 2° giorno del ciclo) in sinergia con FSH ricombinante agli stessi bassi dosaggi del gruppo A di controllo.
Tutti i partner maschili del gruppo B hanno assunto per oltre 90 giorni 3 cps al giorno di Maca polarizzata ( LMWP: 300 mg al dì ).
A partire dall’8° giorno del ciclo la stimolazione ovarica veniva seguita attraverso il dosaggio del 17 Beta estradiolo ed il monitoraggio follicolare.
Nel gruppo A senza fitoterapia andina si sono registrate n° 13 gravidanze pari a 11,8% per ciclo con un pregnancy rates globale dopo 4 tentativi del 20,63%.
Nel gruppo B (Maca polarizz. + FSH ricomb.) si sono registrate n°35 gravidanze pari al 26,51% per ciclo con un pregnancy rates globale dopo 4 tentativi del 55%.
La differenza tra i due gruppi è stata statisticamente significativa ( P < 0.001 )
In sommario il risultato di questo studio indica che l’inseminazione intratubarica (ITI) abbinata ad un’induzione dell’ovulazione con bassi dosaggi di FSH ricombibnante e Maca polarizzata costituisce un metodo efficace, ben tollerato da parte della coppia e praticamente privo di effetti collaterali.
Nonostante che il ruolo di una debole attività LH nella follicologenesi sia tuttora dibattuto, questo studio evidenzia che la maca, grazie all’azione a livello ipotalamico, alla sua moderata attività LH mimetica ed al suggestivo contenuto minerale può incrementare significativamente il pregnancy rates in un programma di inseminazioni intratubariche.
Improving pregnancy rates by means of polarized maca based phytoterapy and intratubal insemination
pubblicato in Controversies in Obstetrics Gynecology & Infertility, september 2001
G. Menaldo, S. Serrano, B. Lopez
Institute of Reproductive Medicine and Psychosomatic Gynaecology(S.Carlo-Ipog), Turin Centre of Research on Medical Bioclimatology-Biotechnologies-Natural Medicine, Milan State University
e-mail: sancarlo@ interlink.it
This prospective randomized study aimed at assessing whether Andean phytotherapy based on polarized Maca (Lepidium Meyenii Walp), combined with low-dose recombinant FSH, may improve pregnancy rates in an intrauterine insemination (ITI) programme. To this end, two homogeneous groups, including 63 selected couples each, were compared. In group A, without Andean phytotherapy, 13 pregnancies were recorded, i.e. 11.8% per cycle, with a 20.63% global pregnancy rate after 4 attempts. In group B (polarized Maca+ recombi nant FSH), 35 pregnancies were recorded, (26.51% per cycle), with 55% global pregnancy rate after 4 attempts. The difference between both was statistically significant (p < 0.001).
In the last few years Maca, a perennial plant of the lepidium meyenii walp peruvanum species, was studied in our Institute for its polyendocrine value and for its balanced mineral content, both particularly fit for use in adjusting cycle-related hormone imbalance and in reproductive medicine. (1,2).Early research on the botanical, phytochemical, and pharmacological properties of this plant includes the studies by Gloria Chacon, that started in 1960 and were published on Peru’s biology review in 1990(3). The authoress demonstrated, in a study carried out on rats inoculated with alkaloids obtained from maca, the regulating and stimulating action of the active ingredients contained in the maca’s tuberous root on samples of rat testes and ovaries. Laboratory tests clearly highlighted a stimulation of ovarian follicles and an increased thickness of the endometrium in female rats, as well as an increased number and motility of sperms in male rats. (4). R. Aquino, V. De Leo, F. De Simone, and colleagues believe that the sterol fraction is mainly constituted by systosterol (45.5%), campesterol (27.3%), and ergosterol (13.7%) (5). The high mineral contents of maca is rather interesting: calcium, iron, magnesium, copper, iodine, silicon, phosphor, potassium, as well as manganese and zinc are found in ideal proportions, that are especially important for man reproduction (Table 1). The root also contains a high concentration of laevulose and fructose, which are known to occur in semen as an energy source for the sperms.The lepidium meyenii root contains aromatic isothiocyanates which demonstrated in various studies their power to increase libido both in animals and in man. (6).Our centre’s case history includes a growing number of infertile couples, rather reluctant to submit to stimulation cycles with high-dose gonadotrophins, due to a fear of multiple pregnancies, as well as to the possible side effects related to ovary hyperstimulation. Indeed, non-customized stimulation protocols, often inadequate, have increased multiple pregnancy rates too much (20 to 30%), which is unacceptable both in terms of increased hyperstimulation risk and of pregnancy and perinatal risks related to the multiple number of foetuses. Frequent news about multiple pregnancies have caused alarm in public opinion as well as among specialists. Thus a growing consensus is recorded for moderate stimulation, especially within the framework of insemination techniques. The prospective randomized study described in this paper goes along this line with the aim of establishing whether Andean phytotherapy (polarized maca) combined with low-dose gonadotrophins, may improve pregnancy rates in an insemination programme based on intratubal insemination (ITI) techniques.
Materials and methods
From January 1999 to January 2001 we treated a sample of 126 couples, suffering from infertility problems for over 3 years, with 242 intratubal insemination (ITI) cycles. First, infertility was precisely diagnosed through laboratory, microbiological, and clinical tests on both partners. Such tests included for women a hormone assay, a post-coital test, vaginal ultrasound scanning, vaginal and cervical swabs with antibiogram, hysterosalpingogra phy, as well as hysteroscopy and laparoscopy in uncertain cases. Male partners were submitted to spermiogram, sperm-culture, mar test, and hormone assay, when necessary. Couples with the following causes of infertility were included in the homologous intratubal insemination programme, upon giving their consent: cervical factor, ovarian factor, unilateral tubal factor, hypogonadotropic hypogonadism, idiopathic infertility, low to moderate male factor with Swim up test > 4 million/ml mobile forms.
Female patients were aged 27 to 39 (mean age 34). As for ovulation induction modes, the patients were divided into two groups:
Group A: induction with recombinant gonadotrophins only (FSH 100 IU from day 3 to day 4 of the cycle; FSH 75 IU from day 5 to the day before intake of 7000 IU of HCG).
Group B: induction with phytotherapy based on polarised maca (LMWP Zener 100-mg tablets: 3tablets daily from day 2 of the cycle to the day of intake of 7000 IU of HCG.From day 3 of the cycle, recombinant gonadotrophins (same as for group A) until the day before intake of 7000 IU of HCG).
Lepidium meyenii (Maca) was administered as 100 mg capsules polarized with 634.7-nm electromagnetic radiation. Such polarization, matching with the DNA resonance polarization, promotes the prompt recognition and use of the substance by the body (the function of the body’s electromagnetic receptors is enabled and enhanced by the 634.7-nm radiation). The polarized form allows the intake of very low quantities of the plant to produce a significant biological effect within a short time (7). Administration to women starting from day 2 of the cycle, improves follicle recruitment, while the intake of 3 100 mg tablets per day in men was extended for 90 days for Group B only, in order to improve the fertilising power of sperms. As to the randomization method, women of group A or group B were selected at random on the day of definition of the treatment plan according to the even or odd series number. Starting from day 8 of the cycle, stimulation was monitored by means of blood oestradiol assay and follicular monitoring (Table 2).7000 IU HCG were administered when the largest follicle reached a diameter > 18-20 mm. Insemination was performed 35-36 hours after HCG administration with the intratubal insemination technique. This provides for gamete transfer directly to the tubal lumen through the transcervical-uterine upgoing tract. Semen priming and capacitation were performed by means of two combined methods: 1 ml of semen by Swim up; the remaining portion by 3 gradients of 45%, 70%, and 95% Pure sperme.
The 126 infertile couples recruited for this prospective randomised study were globally submitted to 242 cycles divided as follows: group A 110 cycles; group B 132 cycles. Both groups were homogeneous by age, term of infertility, and semen parameters. The highest success rate was achieved in group B (polarized Maca + recombinant FSH), with 35 pregnancies equal to 26.51% per cycle, and a 55.50% pregnancy rate after 4 attempts (Table 3). In group A (recombinant FSH) that did not receive phytotherapy, 13 pregnancies were recorded, equal to 11.18 per cycle, with a 20.63% pregnancy rate after 4 cycles. The difference between both groups in terms of per-cycle pregnancy rate and global pregnancy rate (after 4 cycles) is statistically significant (p < 0.001).
One spontaneous miscarriage occurred in group A at week 8 and one spontaneous miscarriage occurred in group B at week 7. While no twin pregnancies were recorded in group A, two pregnancies started in group B with 2 ovum chambers, which spontaneously developed into single pregnancies.
In conclusion, the use of Lepidium meyenii in the form of polarized maca, significantly improves pregnancy rates when combined (Group B) with low-dose gonadotrophins. One of the main factors, in our opinion, is the LH-like action performed through the release and control of both gonadotrophins (FSH, LH). Indeed, a good follicle genesis and steroid genesis resulting into the maturation of quality oocytes requires the combined action of the follicle-stimulating hormone (FSH) and of the luteinising hormone (LH). The latter was recently reinstated by the scientific community, which understood its great importance at very low doses ever since last generation recombinant gonadotrophins were totally deprived of it. (8,9) This small LH quantity secreted by the hypophysis in ideal doses thanks to the hypothalamic action of Lepidium, probably determines the improved quality of oocytes, which are thus more fit for fertilisation and implant. A study by Delphine P. Levy and colleagues (10) supports the theory of two cells, two gonadotrophins; a minimum LH activity is deemed vital for optimal development of the follicle-oocyte set during induction of ovulation, and she thus concludes that a small LH fraction should be included in each type of stimulation protocol. We finally report the recent conclusions drawn by the Filicori group (9). Based on physiological data and test results, they demonstrated that a supplemental LH activity reduces the duration of stimulation, the total quantity of hormone intake and, consequently, the cost of the process. It may further positively influence the quality of oocytes and reduce the risk of ovarian hyperstimultion. Our Group had come to similar conclusions in some prior studies (1,2) ever since 1996. In summary, the results of this study on the treatment of infertility in couples point out to intratubal insemination, combined with ovary stimulation with low-dose recombinant FSH and polarized maca intake, as an effective method, well tolerated by the couples, and virtually free of side effects when at least one of the tubes has a regular function and the male factor is low to moderate (Swim up test > 4 million /ml mobile forms). In addition, the mineral content of maca, well balanced and significant, is ideal for infertility problems, because manganese, calcium, and zinc are available in the correct proportions. Zinc is also vital to protect the sperm nucleus from premature decondensation. Hence the importance of administering polarised maca to male partners too.
1. Menaldo G. La medicina globale negli squilibri ormonali e nella fertilità.Atti del terzo convegno internazionale: Scienze Mediche Integrate, dic 2-10, 1996-Università di Milano.
2. Menaldo G. Ossigeno allotropico e Lepidium Meyeneii (LMWP) nel trattamento dell’infertilità. Atti: Giornate di Medicina Naturale, giugno 26-27,1999- Riolo-Terme-Università di Milano.
3. Chacòn G. La maca ( Lepidium peruvianum) Chacòn sp. Nov. Y su habitad. Revista peruana de Biologia ,3, 171-272, 1990
4. Chacòn G. La importancia de Lepidium peruvianum Chacòn ( MACA)en la alimentaciòn del ser humano y animal. Biblioteca Nac. Del Perù ( reg. 0987). Faculta de Ciencias Biologicas, Univ. Nac. Mayor de San Marcos, Lima- Perù, 1997
5. Aquino R, De Feo V, De Simone F, De Tommasi N, Pizza C. Flora Officinale dell’America Latina, vol. 1, 1996- Salerno.
6. Zheg BL, He K,, Kim CH, Rogers L, Shao Y, Huang ZY, Lu Y, Yan SJ, Qien LC, Zheng QY. Effect of a lipidic extratact from Lepidium meyenii on sexual behaviour in mice and rats.
Urology, 55(4), 598-602,2000
7. Serrano S. Polarizzazione e eccimerizzazione, Atti: Covegno di Medicina Naturale, 2000- Riolo-Terme- Università di Milano.
8. The European recombinat human LH study group. Recombinant Human luteinizing hormone (LH) to support recombinant human follicle- stimulating hormone (FSH)-induced follicular development in LH-and FSH-deficient anovulatory women: a dose-finding study. J.Clin Endocrinol Metab 83, 1507-1514, 1998
9. Filicori M, Cognigni E, Taraborrelli S, Spettoli D, Ciampaglia W, Tabarelli de Fatis C, Pocognoli P, Cantelli B, Boschi S. Luteinizinghormone activity in menotropins optimizes folliculogenesis and
treatment in controlled ovarian stimulation. J. Clin Endocrinol Metab 86, 337-343, 2001
10. Delphine P. Lèvy, Navarro Josè M, Schattman Glenn L, Davis Owen k, Rosenwaks. The Role of LH in ovarian stimulation Exogenous LH:let’s desing the future. Human Reproduction, vol 15, N°11, 2258-2265,2000
Table 1. Active ingredients of Lepidium Meyenii ( Maca)
· Alkaloids: macaine 1,2,3,4
· Phytosterols: -sitosterol (45.5%), campesterol (27.3%), ergosterol (13.6%), B-ecdysone
· Aromatic isothiocynates: benzyl-isothiocyanate, P-methoxy-benzyl-isothiocynate
· Minerals: calcium, iron, magnesium, zinc, manganese, copper, silicon, phosphor, iodine, potassium, aluminium, tin, bismuth
· Vitamins: B1, B2, B12, C, E, A
· Carbohydrates: fructose, laevulose
· Unsaturated essential fatty acids: linoleic (32.6%), oleic (11.1%),
· Essential aminoacids: phenylalanine, histidine, isoleucine, leucine, lysin, methionine, threonine, triptophan, valine.
· Flavonoids, tannins, saponins.